Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites,but the knowledge about the topic remains patchy and superficial.Here ...Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites,but the knowledge about the topic remains patchy and superficial.Here we present the chemical characterization of acatulides A-G(1-7)as architecturally unprecedented macrolides from the solid-state culture of Acaulium album H-JQSF,an arthropod-associated fungus.The acatulide structures were elucidated by spectroscopic analysis,modified Mosher's method and single-crystal X-ray diffraction.The plausible biosynthetic pathways for compounds 1-4 are proposed.Interestingly,acatulides B-D(2-4)and G(7)were demonstrated to be neuroprotective against the 1-methyl-4-phenylpyridinium(MPP+)-induced damage to SH-SY5Y cells and nematode Caenorhabditis elegans(C.elegans).展开更多
Objective To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. Methods Micro-dilution method was used to determine the minimal inhibitory con...Objective To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. Methods Micro-dilution method was used to determine the minimal inhibitory concentrations （MICs） of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PAl and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PAl and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin. Results The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PAl and PA27853 strains through biofilms. PAl and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin. Conclusion Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.展开更多
Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria（NTM） isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in ...Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria（NTM） isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. Methods Four macrolides, including clarithromycin（CLAR）, azithromycin（AZM）, roxithromycin（ROX）, and erythromycin（ERY）, were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23 S r RNA and erm, were analyzed with nucleotide sequence analysis. Results Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191 A and T2221 C on rrl were specific for the M. abscessus complex（MABC）. Seven sites, G2140 A, G2210 C, C2217 G, T2238 C, T2322 C, T2404 C, and A2406 G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192 G, T2358 G, and A2636 G, were observed only in M. fortuitum and one site G2152 A was specific for M. gordonae. The genes erm（39） and erm（41） were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. Conclusion The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23 S r RNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.展开更多
BACKGROUND Diffuse panbronchiolitis(DPB)is a rare,chronic inflammatory lung disease mar-ked by chronic cough,breathlessness,and preceding sinusitis.Symptoms often persist for years and can be misdiagnosed as asthma,pa...BACKGROUND Diffuse panbronchiolitis(DPB)is a rare,chronic inflammatory lung disease mar-ked by chronic cough,breathlessness,and preceding sinusitis.Symptoms often persist for years and can be misdiagnosed as asthma,particularly in children.This report describes a DPB case resolved with long-term azithromycin therapy,em-phasizing the need for a timely and accurate diagnosis.CASE SUMMARY A 12-year-old girl,diagnosed with asthma at age five and managed with inhaled corticosteroids and long-acting beta-2 agonists,developed a history of chronic productive cough and chronic sinusitis for a year.On examination,she exhibited wheezing and coarse crackles.Despite receiving treatment for an asthma exacer-bation,her symptoms did not improve.A chest X-ray revealed reticulonodular infiltration in both lower lungs,prompting further evaluation with high-resolu-tion computed tomography(HRCT).The HRCT confirmed centrilobular nodule opacities,a'tree-in-bud'pattern,and non-tapering bronchi,suggesting DPB.Elevated cold hemagglutinin titers at 128 further supported the diagnosis.Her cough and sinusitis resolved within a month after starting azithromycin therapy,chosen for its anti-inflammatory and immunomodulatory effects.Follow-up HRCT scans after 1 year of continuous treatment showed complete normalization.CONCLUSION This case highlights the importance of early diagnosis and prompt treatment in achieving favorable outcomes for DPB.展开更多
The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechan...The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechanism of action,diverging from established polyene macrolide antibiotics that target ergosterol.The emergence of multidrug-resistant fungal pathogens poses substantial risks to patient health,healthcare infrastructures,and public health at large.The alarming increase in these pathogens is attributed to their capability to withstand numerous antifungal treatments,resulting in escalated morbidity and mortality rates among affected patients.The strategies employed by these pathogens to compromise patient health include modifications at drug target sites,improved efflux mechanisms,and biofilm formation,all of which complicate treatment protocols and extend hospital stays[1].This concerning trend accentuates the urgent need for ongoing monitoring and investigation into innovative antifungal agents and therapeutic approaches to address these resilient pathogens.展开更多
BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has...BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.展开更多
To evaluate the clinical efficacy and safety of oral versus intravenous macrolide antibacterials in managing pediatric pneumonia attributable to Mycoplasma pneumoniae(MP),we conducted a retrospective analysis of clini...To evaluate the clinical efficacy and safety of oral versus intravenous macrolide antibacterials in managing pediatric pneumonia attributable to Mycoplasma pneumoniae(MP),we conducted a retrospective analysis of clinical data from 100 pediatric patients treated in our pediatric outpatient and inpatient departments between January 2020 and August 2023.These patients were divided into two groups based on the method of antibiotic administration:one oral group(n=50)and one intravenous group(n=50).The oral group received either azithromycin or clarithromycin,while the intravenous group received azithromycin or roxithromycin,both at a dosage of 10 mg/kg/d,for a continuous treatment duration of 3-7 d.We compared various clinical parameters,including clinical features,body temperature,white blood cell count,C-reactive protein levels,improvement in chest radiography,recovery time,overall efficacy rate,and incidence of adverse reactions before and after treatment in both groups.Our results reveal ed no statistically significant differences in clinical features,laboratory test results,or chest radiographic manifestations between the two groups before treatment(P>0.05).Following treatment,significant reductions in body temperature,white blood cell count,and C-reactive protein levels were observed in both groups.Additionally,chest radiographic improvement was noted in 100%of cases,with shortened recovery times and an overall efficacy rate of 100%,demonstrating no significant difference between the groups(P>0.05).The incidence of adverse reactions was 6%in the oral group and 8%in the intravenous group,primarily consisting of mild gastrointestinal reactions.No severe adverse reactions were reported,and the difference in incidence between the groups was not statistically significant(P>0.05).Our study underscored the comparable clinical efficacy and safety of oral and intravenous macrolide antibiotics in treating pediatric pneumonia caused by MP.Considering its convenience and cost-effectiveness,oral administration emerged as a favorable treatment option.展开更多
The widespread use of antibiotics has significantly increased their presence in aquatic environments,particularly in sensitive Karst River systems.In this study,the distribution and ecological,human health,and resista...The widespread use of antibiotics has significantly increased their presence in aquatic environments,particularly in sensitive Karst River systems.In this study,the distribution and ecological,human health,and resistance selection risk assessment of 44 antibiotics in the typical Karst River,Lijiang River,were investigated during the influenza season,a period marked by heightened antibiotic usage.27 antibiotics could be found in the water of Lijiang River,among which azithromycin showing the highest concentrations.The concentrations of total antibiotics were in the range 171.70–2003.75 ng/L,with an average value of 704.76 ng/L.Macrolide was the predominant class,constituting an average of 57.65%of the total antibiotic concentrations.Risk assessments revealed that certain antibiotics,especially macrolides,posed moderate to high ecological risks to algae,displayed potential human health risks at low levels and contributed to antimicrobial resistance.Among all the antibiotics,azithromycin was the only one could cause ecological risk to algae,human health risk towards infants and antimicrobial resistance selection risk,which should be identified as the priority antibiotic for control in the Lijiang River during the influenza season.There was no difference in the concentrations,human health and antimicrobial resistance selection risk of antibiotics between mainstream and tributaries of Lijiang River.This study contributes to a better understanding of antibiotic pollution and provides insights into potential risk management practices in vulnerable aquatic systems worldwide.展开更多
A simple and sensitive method was developed for the simultaneous determination of four macrolides in pork using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Homogenized sample was extrac...A simple and sensitive method was developed for the simultaneous determination of four macrolides in pork using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Homogenized sample was extracted with NaH2PO4 buffer and acetonitrile solution,and defatted with n-hexane.Further cleanup was performed on a Sep-Pakt C18 solid-phase extraction cartridge.The compounds were determined by LC-MS/MS operated in positive electrospray ionization mode.The limits of detection(LODs) were 0.5 μg/kg.The average recoveries at three spiked concentration levels of 1.0,5.0,10.0 μg/kg were in the range of 70%-110%,with the intra-day RSD of less than 12.9% and inter-day RSD of less than 13.4%.展开更多
Macrolide antibiotics have been widely used in clinic due to their good antibacterial effects and high safety, but the drug-resistant bacteria appear constantly. To solve the problem of drug resistance in pathogens, s...Macrolide antibiotics have been widely used in clinic due to their good antibacterial effects and high safety, but the drug-resistant bacteria appear constantly. To solve the problem of drug resistance in pathogens, scholars obtain the third generation of macrolide antibiotics, ketolide antibiotics, which are developed by modifying the structure of macrolide antibiotics, thereby efficiently solving the problem. Ketolide antibiotics are a type of erythromycin derivatives with macrolide structure, and the typical drugs mainly include telithromycin, cethromycin and solithromycin, etc . This paper briefly introduced the recent progress of ketolide antibiotics, with an attempt to provide help to the research and development of new macrolide antibiotics.展开更多
Musk macrolides are a kind of rare flavors structurally featuring 14-16 membered rings in the flavour and fragrance industry.While various chemical synthesis routes for musk macrolides exist,there is a growing interes...Musk macrolides are a kind of rare flavors structurally featuring 14-16 membered rings in the flavour and fragrance industry.While various chemical synthesis routes for musk macrolides exist,there is a growing interest in biocatalytic approaches.In this study,a new biocatalytic approach is proposed for the synthesis of musk macrolides from fatty acids using unspecific peroxygenases(UPOs)in combination with lipase.Specifically,the UPO from Marasmius rotula(MroUPO)was utilized as an oxidation catalyst together with the choline oxidase from Arthrobacter nicotinate(AnChOx)for the in situ generation of H_(2)O_(2).The enzymatic cascade process involved the hydroxylation of fatty acids using MroUPO as a catalyst to prepare terminal hydroxylated fatty acids.Under the optimized conditions,14-hydroxy tetradecanoic acid,15-hydroxy pentadecanoic acid and 16-hydroxy hexadecanoic acid were obtained at concentrations of 11.1,18.2 and17.1 mg/L in a 50-mL reaction system,respectively.These hydroxylated fatty acids were then separated and esterified by lipase Novozymes 435 to produce the desired macrolides.Variousω-hydroxy fatty acids were successfully converted into macrolides,with the concentrations of cyclotetradecanolide,cyclopentadecanolide and cyclohexadecanolide reaching 11,29 and 23 mg/L,respectively,in a 10-mL reaction system.This new biocatalytic approach represents a promising method for synthesizing valuable natural flavour compounds.展开更多
As one group of the most widely used oral antibacterial drugs, macrolides have been clinically applied for more than 50 years because of their safety and efficacy. Recently, the non-antibacterial applications of macro...As one group of the most widely used oral antibacterial drugs, macrolides have been clinically applied for more than 50 years because of their safety and efficacy. Recently, the non-antibacterial applications of macrolides are frequently reported, such as the therapy of malignant tumor, exudative pleurisy, pulmonary fibrosis, rheumatoid arthritis, bronchiectasis, asthma, gastrointestinal peristalsis disorders, and so on with new pharmacological effects, including reverse of tumor resistance, anti-chemical adherence, anti-fibrosis, and modulations of gastrointestinal motility as well as immune activity. The in-depth research of marcolides’ non-antibiotic actions can not only extend the application fields of macrolides, but provide a new way to treat some refractory diseases.展开更多
A study of invasive strains of Streptococcus agalactiae (GBS) from Cordoba and Misiones, Argentina;was conducted to determine serotypes, the susceptibility to macrolides and molecular profiles of virulence and resista...A study of invasive strains of Streptococcus agalactiae (GBS) from Cordoba and Misiones, Argentina;was conducted to determine serotypes, the susceptibility to macrolides and molecular profiles of virulence and resistance. We studied 17 strains, recovered from cerebrospinal fluid, blood and cellulite and, a strain of trophoblastic remnants from Misiones. The serotypes were determined by agglutination with sera and phenotypes of resistance to macrolide-lincosamide-streptogramin B (MLSB), were determined with the double-disk test (D-test). The confirmation was performed by E-test by ERI and CLI respectively that determined the minimum inhibitory concentration (MIC). Results were interpreted as recommended by the Clinical and Laboratory Standards Institute (CLSI) 2013. Resistance genes: ermB, ermTR and mefA and the virulence genes: bac, bca, rib, lmb, hylB, scpB, fbsA, fbsB and cylB were investigated by conventional PCR. Serotype III (50%) and Ia (50%) were detected in Cordoba. One strain showed cMLSB phenotype, confirmed by MIC. The same strains showed a resistance gene ermB. All studied virulence genes were detected in 100% of these strains. In Misiones, serotypes were III (72.7%), Ia (18.2%) and Ib (9.1%). All strains were susceptible to CLI and ERI by D-test, confirmed by MIC. None of the strains showed resistance genes. Virulence genes bca, rib, hylB, lmb, fbsA, fbsB and cylB were detected in 100% of the strains, bac in 81.8% and scpB in 90.9%. Our results are in accordance with international data, associating higher frequency of serotype III of invasive neonatal disease followed by Ia. The presence of serotype Ib could indicate a regional difference for Misiones. We highlight the macrolides susceptibility in strains of Misiones and consistency in the results for D-test, MIC and PCR for the single strain resistant phenotype cMLSB from Cordoba. The virulence genes studied were presented with high frequency as expected for invasive strains.展开更多
SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other app...SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.展开更多
Since the discovery of penicillin by Fleming in 1928, the knowledge of the antibiotics’ spectrum and mechanism of action has been steadily increasing. Antibiotics became an effective tool in the fight against many pa...Since the discovery of penicillin by Fleming in 1928, the knowledge of the antibiotics’ spectrum and mechanism of action has been steadily increasing. Antibiotics became an effective tool in the fight against many pathogens, changing the prognosis of outcome for many serious diseases. It is already known that antibiotics not only have the antibacterial activity, but many of them—e.g. macrolides, sulphonamides and tetracyclines—have immunomodulating effect, affecting functions of lymphocytes, macrophages and costimulatory molecules, macrophage migration and phagocytosis, as well as proinflammatory cytokine secretion. The expanding knowledge of the effects of antibiotics on the immune system has brought with it new applications of antibiotics in organ transplantation, invasive cardiology and treatment of autoimmune diseases such as rheumatoid arthritis or asthma.展开更多
[Objective]The aim is to provide data support for the prevention and control of pollution of exogenous chemical in pig breeding industry.[Methods]Solid-phase extraction（SPE）and tandem mass（LC-MS/MS）were used for d...[Objective]The aim is to provide data support for the prevention and control of pollution of exogenous chemical in pig breeding industry.[Methods]Solid-phase extraction（SPE）and tandem mass（LC-MS/MS）were used for determining four classes（tetracyclines,quinolones,macrolides and sulfonamides）of 10 common veterinary antibiotics in groundwater of an important pig breeding base in the Yangtze River Delta region of China.[Results]Results revealed the total concentration of the ten antibiotics in urban rivers ranged from 20.1 ng /L to 61.2 ng /L.The highest proportion was taken by tetracyclines,account for 95%,the concentration was up to 44.0 ng /L.Quinolones shared the second largest proportion of total concentration,about 29%,the concentration was up to 21.6 ng /L,while concentration of sulfonamides and macrolides were respectively below 2.7 ng /L and 6.3 ng /L.The highest total concentration of the ten antibiotics in rural rivers was up to 467 ng /L,60% of which was shared by tetracyclines,the highest concentration of tetracyclines was 253 ng /L.Sulfonamides share 20% of the total concentration,the highest concentration of it was 165 ng /L.The highest concentration of macrolides and quinolones was 14.6 ng /L and 14.5 ng /L,respectively.[Conclusion] Antibiotics＇ pollution in town rivers is more serious than urban rivers＇ pollution caused by antibiotics.展开更多
Objective The aim of this study is to investigate the macrolide resistance rate and molecular type with multiple-locus variable-number tandem-repeat analysis(MLVA)of Mycoplasma pneumoniae of Beijing in 2016 in pediatr...Objective The aim of this study is to investigate the macrolide resistance rate and molecular type with multiple-locus variable-number tandem-repeat analysis(MLVA)of Mycoplasma pneumoniae of Beijing in 2016 in pediatric patients.Methods Real-time quantitative polymerase chain reaction(PCR)was used to identify M.pneumoniae,and MLVA was performed.The domain V of the 23 S rRNA was sequenced to detect macrolide-resistant point mutations.We also investigated the activities of antibiotics against M.pneumoniae isolates in vitro.Results The PCR detection rate of M.pneumoniae in children in Beijing was 40%,and the macrolide resistance rate was 66%.The A2063 G mutation in the 23 S rRNA V region is the dominant mutation(137/146,93.84%),whereas the A2064 G mutation is rare(9/146,6.16%).Seventy-three samples were typed successfully by MLVA typing,including 86.3%(63/73)were MLVA type 4-5-7-2,and 13.7%(10/73)were MLVA type 3-5-6-2.No other types were found.No strains were resistant to levofloxacin or tetracycline.Conclusion In 2016,a specific decrease in the macrolide resistance rate occurred in Beijing.The detection rate and macrolide resistance rate of outpatients are lower than those of inpatients.The A2063 G mutants M.pneumoniae have high levels of resistance to erythromycin and azithromycin.The primary MLVA type is 4-5-7-2,followed by 3-5-6-2.No other MLVA types were detected.No strains resistant to tetracycline or levofloxacin were found in vitro.展开更多
A 24-membered ring macrolide compound,macrolactin A has potential applications in pharmaceuticals for its anti-infectious and antiviral activity.In this study,macrolactin A was produced by a marine bacterium,which was...A 24-membered ring macrolide compound,macrolactin A has potential applications in pharmaceuticals for its anti-infectious and antiviral activity.In this study,macrolactin A was produced by a marine bacterium,which was identified as Bacillus subtilis by 16S ribosomal RNA(rRNA) sequence analysis.Electrospray ionization mass spectrometry(ESI/MS) and nuclear magnetic resonance(NMR) spectroscopy analyses were used to characterize this compound.To improve the production,response surface methodology(RSM) involving Box-Behnken design(BBD) was employed.Faeces bombycis,the main by-product in sericulture,was used as a nitrogen source in fermentation.The interactions between three significant factors,F.bombycis,soluble starch,and(NH4)2SO4 were investigated.A quadratic model was constructed to fit the production and the factors.Optimum medium composition was obtained by analysis of the model.When cultivated in the optimum medium,the production of macrolactin A was increased to 851 mg/L,2.7 times as compared to the original.This study is also useful to find another way in utilizing F.bombycis.展开更多
A recent study showed that erythromycin(ERY)exposure caused hormesis in a model alga(Raphidocelis subcapitata)where the growth was promoted at an environmentally realistic concentration(4μg/L)but inhibited at two hig...A recent study showed that erythromycin(ERY)exposure caused hormesis in a model alga(Raphidocelis subcapitata)where the growth was promoted at an environmentally realistic concentration(4μg/L)but inhibited at two higher concentrations(80 and 120μg/L),associated with opposite actions of certain signaling pathways(e.g.,xenobiotic metabolism,DNA replication).However,these transcriptional alterations remain to be investigated and verified at the metabolomic level.This study uncovered metabolomic profiles and detailed toxic mechanisms of ERY in R.subcapitata using untargetedmetabolomics.Themetabolomic analysis showed that metabolomic pathways including ABC transporters,fatty acid biosynthesis and purine metabolism were associated with growth promotion in algae treated with 4μg/L ERY.An overcompensation was possibly activated by the low level of ERY in algae where more resources were reallocated to efficiently restore the temporary impairments,ultimately leading to the outperformance of growth.By contrast,algal growth inhibition in the 80 and 120μg/L ERY treatments was likely attributed to the dysfunction of metabolomic pathways related to ABC transporters,energy metabolism and metabolism of nucleosides.Apart from binding of ERY to the 50S subunit of ribosomes to inhibit protein translation as in bacteria,the data presented here indicate that inhibition of protein translation and growth performance of algae by ERY may also result from the suppression of amino acid biosynthesis and aminoacyl-tRNA biosynthesis.This study provides novel insights into the dose-dependent toxicity of ERY on R.subcapitata.展开更多
基金co-financed by the grants from National Nature Science Foundation of China(Nos.81991523 and 81991524)National Science and Technology Innovation 2030-Major Program of“Brain Science and Brain-Like Research”(No.2022ZD0211804)。
文摘Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites,but the knowledge about the topic remains patchy and superficial.Here we present the chemical characterization of acatulides A-G(1-7)as architecturally unprecedented macrolides from the solid-state culture of Acaulium album H-JQSF,an arthropod-associated fungus.The acatulide structures were elucidated by spectroscopic analysis,modified Mosher's method and single-crystal X-ray diffraction.The plausible biosynthetic pathways for compounds 1-4 are proposed.Interestingly,acatulides B-D(2-4)and G(7)were demonstrated to be neuroprotective against the 1-methyl-4-phenylpyridinium(MPP+)-induced damage to SH-SY5Y cells and nematode Caenorhabditis elegans(C.elegans).
文摘Objective To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. Methods Micro-dilution method was used to determine the minimal inhibitory concentrations （MICs） of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PAl and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PAl and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin. Results The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PAl and PA27853 strains through biofilms. PAl and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin. Conclusion Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.
基金supported by the Key Project of the State Key Laboratory for Infectious Disease Prevention and Control[2014SKLID104]the National Key Programs of Mega Infectious Diseases[2013ZX10003002-001]
文摘Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria（NTM） isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. Methods Four macrolides, including clarithromycin（CLAR）, azithromycin（AZM）, roxithromycin（ROX）, and erythromycin（ERY）, were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23 S r RNA and erm, were analyzed with nucleotide sequence analysis. Results Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191 A and T2221 C on rrl were specific for the M. abscessus complex（MABC）. Seven sites, G2140 A, G2210 C, C2217 G, T2238 C, T2322 C, T2404 C, and A2406 G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192 G, T2358 G, and A2636 G, were observed only in M. fortuitum and one site G2152 A was specific for M. gordonae. The genes erm（39） and erm（41） were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. Conclusion The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23 S r RNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.
文摘BACKGROUND Diffuse panbronchiolitis(DPB)is a rare,chronic inflammatory lung disease mar-ked by chronic cough,breathlessness,and preceding sinusitis.Symptoms often persist for years and can be misdiagnosed as asthma,particularly in children.This report describes a DPB case resolved with long-term azithromycin therapy,em-phasizing the need for a timely and accurate diagnosis.CASE SUMMARY A 12-year-old girl,diagnosed with asthma at age five and managed with inhaled corticosteroids and long-acting beta-2 agonists,developed a history of chronic productive cough and chronic sinusitis for a year.On examination,she exhibited wheezing and coarse crackles.Despite receiving treatment for an asthma exacer-bation,her symptoms did not improve.A chest X-ray revealed reticulonodular infiltration in both lower lungs,prompting further evaluation with high-resolu-tion computed tomography(HRCT).The HRCT confirmed centrilobular nodule opacities,a'tree-in-bud'pattern,and non-tapering bronchi,suggesting DPB.Elevated cold hemagglutinin titers at 128 further supported the diagnosis.Her cough and sinusitis resolved within a month after starting azithromycin therapy,chosen for its anti-inflammatory and immunomodulatory effects.Follow-up HRCT scans after 1 year of continuous treatment showed complete normalization.CONCLUSION This case highlights the importance of early diagnosis and prompt treatment in achieving favorable outcomes for DPB.
基金supported by the National Natural Science Foundation of China(82460111)the The First People’s Hospital of Yunnan Province Talent Project program(No.KHBS-2022013,KHYJ-2025-04-02,2022-KHRCBZ-B03)+4 种基金the Kunming Medical University Joint Special Project on Applied Basic Research(202301AY070001-210)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04)Yunnan Foundmental basical research project(202301AT070034)the Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases(No.2022ZDKFKT001)the Open Project of Yunnan Provincial Clinical Medical Research Center for Elderly Diseases(No.:2023YJZX-LN03/13 of 202102AA3100692023).
文摘The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechanism of action,diverging from established polyene macrolide antibiotics that target ergosterol.The emergence of multidrug-resistant fungal pathogens poses substantial risks to patient health,healthcare infrastructures,and public health at large.The alarming increase in these pathogens is attributed to their capability to withstand numerous antifungal treatments,resulting in escalated morbidity and mortality rates among affected patients.The strategies employed by these pathogens to compromise patient health include modifications at drug target sites,improved efflux mechanisms,and biofilm formation,all of which complicate treatment protocols and extend hospital stays[1].This concerning trend accentuates the urgent need for ongoing monitoring and investigation into innovative antifungal agents and therapeutic approaches to address these resilient pathogens.
基金Supported by Baoding Science and Technology Plan Project,No.2272P011Hebei Province Scientific Research Project,No.20241734Hebei Natural Science Foundation Project,No.H2024104011.
文摘BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.
文摘To evaluate the clinical efficacy and safety of oral versus intravenous macrolide antibacterials in managing pediatric pneumonia attributable to Mycoplasma pneumoniae(MP),we conducted a retrospective analysis of clinical data from 100 pediatric patients treated in our pediatric outpatient and inpatient departments between January 2020 and August 2023.These patients were divided into two groups based on the method of antibiotic administration:one oral group(n=50)and one intravenous group(n=50).The oral group received either azithromycin or clarithromycin,while the intravenous group received azithromycin or roxithromycin,both at a dosage of 10 mg/kg/d,for a continuous treatment duration of 3-7 d.We compared various clinical parameters,including clinical features,body temperature,white blood cell count,C-reactive protein levels,improvement in chest radiography,recovery time,overall efficacy rate,and incidence of adverse reactions before and after treatment in both groups.Our results reveal ed no statistically significant differences in clinical features,laboratory test results,or chest radiographic manifestations between the two groups before treatment(P>0.05).Following treatment,significant reductions in body temperature,white blood cell count,and C-reactive protein levels were observed in both groups.Additionally,chest radiographic improvement was noted in 100%of cases,with shortened recovery times and an overall efficacy rate of 100%,demonstrating no significant difference between the groups(P>0.05).The incidence of adverse reactions was 6%in the oral group and 8%in the intravenous group,primarily consisting of mild gastrointestinal reactions.No severe adverse reactions were reported,and the difference in incidence between the groups was not statistically significant(P>0.05).Our study underscored the comparable clinical efficacy and safety of oral and intravenous macrolide antibiotics in treating pediatric pneumonia caused by MP.Considering its convenience and cost-effectiveness,oral administration emerged as a favorable treatment option.
基金Knowledge Innovation Program of Wuhan-Shugung Project,Grant/Award Number:2023020201020363。
文摘The widespread use of antibiotics has significantly increased their presence in aquatic environments,particularly in sensitive Karst River systems.In this study,the distribution and ecological,human health,and resistance selection risk assessment of 44 antibiotics in the typical Karst River,Lijiang River,were investigated during the influenza season,a period marked by heightened antibiotic usage.27 antibiotics could be found in the water of Lijiang River,among which azithromycin showing the highest concentrations.The concentrations of total antibiotics were in the range 171.70–2003.75 ng/L,with an average value of 704.76 ng/L.Macrolide was the predominant class,constituting an average of 57.65%of the total antibiotic concentrations.Risk assessments revealed that certain antibiotics,especially macrolides,posed moderate to high ecological risks to algae,displayed potential human health risks at low levels and contributed to antimicrobial resistance.Among all the antibiotics,azithromycin was the only one could cause ecological risk to algae,human health risk towards infants and antimicrobial resistance selection risk,which should be identified as the priority antibiotic for control in the Lijiang River during the influenza season.There was no difference in the concentrations,human health and antimicrobial resistance selection risk of antibiotics between mainstream and tributaries of Lijiang River.This study contributes to a better understanding of antibiotic pollution and provides insights into potential risk management practices in vulnerable aquatic systems worldwide.
文摘A simple and sensitive method was developed for the simultaneous determination of four macrolides in pork using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Homogenized sample was extracted with NaH2PO4 buffer and acetonitrile solution,and defatted with n-hexane.Further cleanup was performed on a Sep-Pakt C18 solid-phase extraction cartridge.The compounds were determined by LC-MS/MS operated in positive electrospray ionization mode.The limits of detection(LODs) were 0.5 μg/kg.The average recoveries at three spiked concentration levels of 1.0,5.0,10.0 μg/kg were in the range of 70%-110%,with the intra-day RSD of less than 12.9% and inter-day RSD of less than 13.4%.
基金Supported by National Sci-tech Support Plant during Twelfth Five-Year Plan(2015BAD1101)Earmarked Fund for China Agriculture Research System(CAR-38)~~
文摘Macrolide antibiotics have been widely used in clinic due to their good antibacterial effects and high safety, but the drug-resistant bacteria appear constantly. To solve the problem of drug resistance in pathogens, scholars obtain the third generation of macrolide antibiotics, ketolide antibiotics, which are developed by modifying the structure of macrolide antibiotics, thereby efficiently solving the problem. Ketolide antibiotics are a type of erythromycin derivatives with macrolide structure, and the typical drugs mainly include telithromycin, cethromycin and solithromycin, etc . This paper briefly introduced the recent progress of ketolide antibiotics, with an attempt to provide help to the research and development of new macrolide antibiotics.
基金supported by the Key Realm R&D Program of Guangdong Province(2022B0202050003)National Natural Science Foundation of China(31930084,32001633)。
文摘Musk macrolides are a kind of rare flavors structurally featuring 14-16 membered rings in the flavour and fragrance industry.While various chemical synthesis routes for musk macrolides exist,there is a growing interest in biocatalytic approaches.In this study,a new biocatalytic approach is proposed for the synthesis of musk macrolides from fatty acids using unspecific peroxygenases(UPOs)in combination with lipase.Specifically,the UPO from Marasmius rotula(MroUPO)was utilized as an oxidation catalyst together with the choline oxidase from Arthrobacter nicotinate(AnChOx)for the in situ generation of H_(2)O_(2).The enzymatic cascade process involved the hydroxylation of fatty acids using MroUPO as a catalyst to prepare terminal hydroxylated fatty acids.Under the optimized conditions,14-hydroxy tetradecanoic acid,15-hydroxy pentadecanoic acid and 16-hydroxy hexadecanoic acid were obtained at concentrations of 11.1,18.2 and17.1 mg/L in a 50-mL reaction system,respectively.These hydroxylated fatty acids were then separated and esterified by lipase Novozymes 435 to produce the desired macrolides.Variousω-hydroxy fatty acids were successfully converted into macrolides,with the concentrations of cyclotetradecanolide,cyclopentadecanolide and cyclohexadecanolide reaching 11,29 and 23 mg/L,respectively,in a 10-mL reaction system.This new biocatalytic approach represents a promising method for synthesizing valuable natural flavour compounds.
文摘As one group of the most widely used oral antibacterial drugs, macrolides have been clinically applied for more than 50 years because of their safety and efficacy. Recently, the non-antibacterial applications of macrolides are frequently reported, such as the therapy of malignant tumor, exudative pleurisy, pulmonary fibrosis, rheumatoid arthritis, bronchiectasis, asthma, gastrointestinal peristalsis disorders, and so on with new pharmacological effects, including reverse of tumor resistance, anti-chemical adherence, anti-fibrosis, and modulations of gastrointestinal motility as well as immune activity. The in-depth research of marcolides’ non-antibiotic actions can not only extend the application fields of macrolides, but provide a new way to treat some refractory diseases.
文摘A study of invasive strains of Streptococcus agalactiae (GBS) from Cordoba and Misiones, Argentina;was conducted to determine serotypes, the susceptibility to macrolides and molecular profiles of virulence and resistance. We studied 17 strains, recovered from cerebrospinal fluid, blood and cellulite and, a strain of trophoblastic remnants from Misiones. The serotypes were determined by agglutination with sera and phenotypes of resistance to macrolide-lincosamide-streptogramin B (MLSB), were determined with the double-disk test (D-test). The confirmation was performed by E-test by ERI and CLI respectively that determined the minimum inhibitory concentration (MIC). Results were interpreted as recommended by the Clinical and Laboratory Standards Institute (CLSI) 2013. Resistance genes: ermB, ermTR and mefA and the virulence genes: bac, bca, rib, lmb, hylB, scpB, fbsA, fbsB and cylB were investigated by conventional PCR. Serotype III (50%) and Ia (50%) were detected in Cordoba. One strain showed cMLSB phenotype, confirmed by MIC. The same strains showed a resistance gene ermB. All studied virulence genes were detected in 100% of these strains. In Misiones, serotypes were III (72.7%), Ia (18.2%) and Ib (9.1%). All strains were susceptible to CLI and ERI by D-test, confirmed by MIC. None of the strains showed resistance genes. Virulence genes bca, rib, hylB, lmb, fbsA, fbsB and cylB were detected in 100% of the strains, bac in 81.8% and scpB in 90.9%. Our results are in accordance with international data, associating higher frequency of serotype III of invasive neonatal disease followed by Ia. The presence of serotype Ib could indicate a regional difference for Misiones. We highlight the macrolides susceptibility in strains of Misiones and consistency in the results for D-test, MIC and PCR for the single strain resistant phenotype cMLSB from Cordoba. The virulence genes studied were presented with high frequency as expected for invasive strains.
文摘SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.
文摘Since the discovery of penicillin by Fleming in 1928, the knowledge of the antibiotics’ spectrum and mechanism of action has been steadily increasing. Antibiotics became an effective tool in the fight against many pathogens, changing the prognosis of outcome for many serious diseases. It is already known that antibiotics not only have the antibacterial activity, but many of them—e.g. macrolides, sulphonamides and tetracyclines—have immunomodulating effect, affecting functions of lymphocytes, macrophages and costimulatory molecules, macrophage migration and phagocytosis, as well as proinflammatory cytokine secretion. The expanding knowledge of the effects of antibiotics on the immune system has brought with it new applications of antibiotics in organ transplantation, invasive cardiology and treatment of autoimmune diseases such as rheumatoid arthritis or asthma.
文摘[Objective]The aim is to provide data support for the prevention and control of pollution of exogenous chemical in pig breeding industry.[Methods]Solid-phase extraction（SPE）and tandem mass（LC-MS/MS）were used for determining four classes（tetracyclines,quinolones,macrolides and sulfonamides）of 10 common veterinary antibiotics in groundwater of an important pig breeding base in the Yangtze River Delta region of China.[Results]Results revealed the total concentration of the ten antibiotics in urban rivers ranged from 20.1 ng /L to 61.2 ng /L.The highest proportion was taken by tetracyclines,account for 95%,the concentration was up to 44.0 ng /L.Quinolones shared the second largest proportion of total concentration,about 29%,the concentration was up to 21.6 ng /L,while concentration of sulfonamides and macrolides were respectively below 2.7 ng /L and 6.3 ng /L.The highest total concentration of the ten antibiotics in rural rivers was up to 467 ng /L,60% of which was shared by tetracyclines,the highest concentration of tetracyclines was 253 ng /L.Sulfonamides share 20% of the total concentration,the highest concentration of it was 165 ng /L.The highest concentration of macrolides and quinolones was 14.6 ng /L and 14.5 ng /L,respectively.[Conclusion] Antibiotics＇ pollution in town rivers is more serious than urban rivers＇ pollution caused by antibiotics.
基金supported by the National Natural Science Foundation of China[Grant No.81271890]Beijing Municipal Science&Technology Commission Grant[No.Z161100000116088 and Z1711000017081]
文摘Objective The aim of this study is to investigate the macrolide resistance rate and molecular type with multiple-locus variable-number tandem-repeat analysis(MLVA)of Mycoplasma pneumoniae of Beijing in 2016 in pediatric patients.Methods Real-time quantitative polymerase chain reaction(PCR)was used to identify M.pneumoniae,and MLVA was performed.The domain V of the 23 S rRNA was sequenced to detect macrolide-resistant point mutations.We also investigated the activities of antibiotics against M.pneumoniae isolates in vitro.Results The PCR detection rate of M.pneumoniae in children in Beijing was 40%,and the macrolide resistance rate was 66%.The A2063 G mutation in the 23 S rRNA V region is the dominant mutation(137/146,93.84%),whereas the A2064 G mutation is rare(9/146,6.16%).Seventy-three samples were typed successfully by MLVA typing,including 86.3%(63/73)were MLVA type 4-5-7-2,and 13.7%(10/73)were MLVA type 3-5-6-2.No other types were found.No strains were resistant to levofloxacin or tetracycline.Conclusion In 2016,a specific decrease in the macrolide resistance rate occurred in Beijing.The detection rate and macrolide resistance rate of outpatients are lower than those of inpatients.The A2063 G mutants M.pneumoniae have high levels of resistance to erythromycin and azithromycin.The primary MLVA type is 4-5-7-2,followed by 3-5-6-2.No other MLVA types were detected.No strains resistant to tetracycline or levofloxacin were found in vitro.
基金Project supported by the Science and Technology Department of Zhejiang Province,China(No.2009C33019)the IndustryUniversity-Research Institution Alliance for Microbial Medicine Technology Innovation and New Drug Development of China (No.2010ZX090401-403)the National Science and Technology Major Project of New Drug of China(Nos.2011ZX09201-101 and 2012ZX09103101-075)
文摘A 24-membered ring macrolide compound,macrolactin A has potential applications in pharmaceuticals for its anti-infectious and antiviral activity.In this study,macrolactin A was produced by a marine bacterium,which was identified as Bacillus subtilis by 16S ribosomal RNA(rRNA) sequence analysis.Electrospray ionization mass spectrometry(ESI/MS) and nuclear magnetic resonance(NMR) spectroscopy analyses were used to characterize this compound.To improve the production,response surface methodology(RSM) involving Box-Behnken design(BBD) was employed.Faeces bombycis,the main by-product in sericulture,was used as a nitrogen source in fermentation.The interactions between three significant factors,F.bombycis,soluble starch,and(NH4)2SO4 were investigated.A quadratic model was constructed to fit the production and the factors.Optimum medium composition was obtained by analysis of the model.When cultivated in the optimum medium,the production of macrolactin A was increased to 851 mg/L,2.7 times as compared to the original.This study is also useful to find another way in utilizing F.bombycis.
基金supported by the National Natural Science Foundation of China (No. 42101077)The Key Research and Development Program of Shaan Xi Province (No. 2020SF-387)ShaanXi Thousand Talent Program for Young Outstanding Scientists (No. 334041900007)
文摘A recent study showed that erythromycin(ERY)exposure caused hormesis in a model alga(Raphidocelis subcapitata)where the growth was promoted at an environmentally realistic concentration(4μg/L)but inhibited at two higher concentrations(80 and 120μg/L),associated with opposite actions of certain signaling pathways(e.g.,xenobiotic metabolism,DNA replication).However,these transcriptional alterations remain to be investigated and verified at the metabolomic level.This study uncovered metabolomic profiles and detailed toxic mechanisms of ERY in R.subcapitata using untargetedmetabolomics.Themetabolomic analysis showed that metabolomic pathways including ABC transporters,fatty acid biosynthesis and purine metabolism were associated with growth promotion in algae treated with 4μg/L ERY.An overcompensation was possibly activated by the low level of ERY in algae where more resources were reallocated to efficiently restore the temporary impairments,ultimately leading to the outperformance of growth.By contrast,algal growth inhibition in the 80 and 120μg/L ERY treatments was likely attributed to the dysfunction of metabolomic pathways related to ABC transporters,energy metabolism and metabolism of nucleosides.Apart from binding of ERY to the 50S subunit of ribosomes to inhibit protein translation as in bacteria,the data presented here indicate that inhibition of protein translation and growth performance of algae by ERY may also result from the suppression of amino acid biosynthesis and aminoacyl-tRNA biosynthesis.This study provides novel insights into the dose-dependent toxicity of ERY on R.subcapitata.
