Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of th...Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the Pub Med database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals(including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agentseither as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions.展开更多
Immunoassays greatly contribute to veterinary drug residue analysis. However, there are few reports on detecting neomycin residues by immunoassay. Here, a rapid and sensitive chemiluminescent enzyme immunoassay （CLIE...Immunoassays greatly contribute to veterinary drug residue analysis. However, there are few reports on detecting neomycin residues by immunoassay. Here, a rapid and sensitive chemiluminescent enzyme immunoassay （CLIEA） was successfully developed for neomycin residue analysis. CLIEA demonstrated good cross-reactivity for neomycin, and the IC50 value was 2.4 ng/mL in buffer.展开更多
A simple, fast and reliable method, using high performance anion chromatography with pulsed amperometric detection, had been developed for the analysis of neomycin in water samples. The elution and separation were car...A simple, fast and reliable method, using high performance anion chromatography with pulsed amperometric detection, had been developed for the analysis of neomycin in water samples. The elution and separation were carried out with an isocratic mobile phase, containing 10 mmol/L NaOH. The influence of the concentration and pH of the mobile phase on the separation and detection was investigated. A quadruple-potential waveform used for the detection was optimized. The detection limit of neomycin was down to 0.027 μg/mL. The linearity of neomycin calibration curve ranged from 0.050 to 0.505 μg/mL with correlation coefficient of 0.9997. R.S.D. (n = 11) was 4.0%.展开更多
Objective The role of selective decontamination with oral antibiotics(OABs)and mechanical bowel preparation(MBP)prior to elective colorectal surgery is still widely debated.The objective of this study was to compare t...Objective The role of selective decontamination with oral antibiotics(OABs)and mechanical bowel preparation(MBP)prior to elective colorectal surgery is still widely debated.The objective of this study was to compare the outcomes of selective decontamination with neomycin,metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation.Methods Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital,a major Australian tertiary referral hospital,between June 2017 and January 2023.Comparisons between short-term outcomes of OAB+MBP and MBP/no preparation were made using prospectively collected data on length of stay(LOS),readmission,mortality within 30 days,anastomotic leakage(AL),surgical site infection(SSI),urinary tract infection,deep venous thrombosis and/or pulmonary embolism,pneumonia,and ileus.Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery.The Mann-Whitney U test was used to analyse continuous data,and the chi-square test was used for categorical data.Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL.Results Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI(2.7%vs.7.6%,p=0.043)and overall complications(32.7%vs.44.6%,p=0.020),particularly Clavien-Dindo 1 complications(7.3%vs.16.5%,p=0.009).However,the differences in AL(2.7%vs.4.5%,p=0.369)and organ/space SSI(1.3%vs.3.7%,p=0.327)were not statistically significant.The median LOS(6 d vs.6 d,p=0.370)was not different between the groups.Conclusion Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications.There was a trend to toward a lower AL,but this difference was not statistically significant.展开更多
Objective: Mastitis is one of the most costly diseases in dairy cows, which greatly decreases milk production. Use of antibiotics in cattle leads to antibiotic-resistance of mastitis-causing bacteria. The present stud...Objective: Mastitis is one of the most costly diseases in dairy cows, which greatly decreases milk production. Use of antibiotics in cattle leads to antibiotic-resistance of mastitis-causing bacteria. The present study aimed to investigate synergistic effect of silver nanoparticles (AgNPs) with neomycin or gentamicin antibiotic on mastitis-causing Staphylococcus aureus. Materials and Methods: In this study, 46 samples of milk were taken from the cows with clinical and subclinical mastitis during the august-October 2015 sampling period. In addition to biochemical tests, nuc gene amplification by PCR was used to identify strains of Staphylococcus aureus. Disk diffusion test and microdilution were performed to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional Inhibitory Concentration (FIC) index was calculated to determine the interaction between a combination of AgNPs and each one of the antibiotics. Results: Twenty strains of Staphylococcus aureus were isolated from 46 milk samples and were confirmed by PCR. Based on disk diffusion test, 35%, 10% and 55% of the strains were respectively susceptible, moderately susceptible and resistant to gentamicin. In addition, 35%, 15% and 50% of the strains were respectively susceptible, moderately susceptible and resistant to neomycin. According to FIC index, gentamicin antibiotic and AgNPs had synergistic effects in 50% of the strains. Furthermore, neomycin antibiotic and AgNPs had synergistic effects in 45% of the strains. Conclusion: It could be concluded that a combination of AgNPs with either gentamicin or neomycin showed synergistic antibacterial properties in Staphylococcus aureus isolates from mastitis. In addition, some hypotheses were proposed to explain antimicrobial mechanism of the combination.展开更多
Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 16...Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 169 patients presenting with clinical criteria for vaginitis were included in an open, multicenter trial. Vaginal samples were taken for microbiological analyses and a triple-combination product of nystatin, neomycin and polymyxin B was then started as local treatment, without waiting for the test results. The treatment was continued with the usual dosage (1 vaginal capsule at bedtime for 12 days) for vaginal infections in the scope of the combination product with approved labeling. A second vaginal sample was performed at the end of the treatment. The main efficacy criterion was the clinical success rate (cure or improvement of the clinical signs and symptoms) according to the investigator.Results: 93 patients were included in the efficacy population. Non-exclusively fungal vaginitis (strictly bacterial or bacterial + fungal) represented 31.2% of the cases. The clinical success rate was 97.8% according to the investigator and 95.7% according to the patients. The microbiological success rate was 81.3%, with no differences between etiologies (Candida spp., bacteria or both). The combination product was well-tolerated, despite the local inflammation before treatment. Discussion and conclusion: Given the etiological diversity of vaginitis, this trial supports the efficacy of a triple-combination product (nystatin, neomycin, polymyxin B) as a first-line local treatment of Candida, bacterial or mixed vaginitis.展开更多
Neomycins are a group of aminoglycoside antibiotics with both clinical and agricultural applications.To elucidate the regulatory mechanism of neomycin biosynthesis,we completed draft genome sequencing of a neomycin pr...Neomycins are a group of aminoglycoside antibiotics with both clinical and agricultural applications.To elucidate the regulatory mechanism of neomycin biosynthesis,we completed draft genome sequencing of a neomycin producer Streptomyces fradiae CGMCC 4.7387 from marine sediments,and the neomycin biosynthesis gene cluster was identified.Inactivation of the afsA-g gene encoding a γ-butyrolactone(GBL) synthase in S.fradiae CGMCC 4.7387 resulted in a significant decrease of neomycin production.Quantitative RT-PCR analysis revealed that the transcriptional level of neoR and the aphA-neoGH operon were reduced in the afsA-g::aac(3)Ⅳ mutant.Interestingly,a conserved binding site of AdpA,a key activator in the GBL regulatory cascade,was discovered upstream of neoR,a putative regulatory gene encoding a protein with an ATPase domain and a tetratricopeptide repeat domain.When neoR was inactivated,the neomycin production was reduced about 40%in comparison with the WT strain.Quantitative RT-PCR analysis revealed that the transcriptional levels of genes in the aphA-neoGH operon were reduced clearly in the neoR::aac(3)Ⅳ mutant.Finally,the titers of neomycin were improved considerably by overexpression of qfsA-gand neoR in S.fradiae CGMCC 4.7387.展开更多
Neomycin belongs to the family of 2-deoxystreptamine-containing aminoglycoside antibiotics.It is widely used for bacterial infections,targeting most gram-negative and some gram-positive bacteria.Neomycin has also been...Neomycin belongs to the family of 2-deoxystreptamine-containing aminoglycoside antibiotics.It is widely used for bacterial infections,targeting most gram-negative and some gram-positive bacteria.Neomycin has also been reported to show antiviral activity.Here,we evaluated the toxicity of neomycin sulfate,and investigated its effect on non-specific immunity and viral infection in crucian carp(Carassius auratus gibelio).The safe concentration of neomycin sulfate for crucian carp was determined to be 102.9 mg/kg in vivo.In oxidative damage assays,neomycin sulfate increased superoxide dismutase and catalase activity and decreased malondialdehyde in the liver of crucian carp.In non-specific blood immune assays,the white blood cell count and complement 3 content significantly increased after neomycin sulfate treatment,while no significant changes were observed in antibacterial or lysozyme activity.In a challenge test,neomycin sulfate protected the crucian carp from cyprinid herpesvirus 2(CyHV-2)infection and inhibited CyHV-2 replication.In cytotoxicity assays,low concentrations of neomycin sulfate had no cytotoxicity on cells from the fins of crucian carp.The results of the present study indicate that oral administration of neomycin sulfate reduced oxidative damage,enhanced immunity and provided protection against CyHV-2 in crucian carp.展开更多
Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics(gentamicin,amikacin,neomycin)and platinum anti-tumor drugs(cisplatin,carboplatin).The inner ear and kidney share similar...Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics(gentamicin,amikacin,neomycin)and platinum anti-tumor drugs(cisplatin,carboplatin).The inner ear and kidney share similarities in drug deposition and toxicity,but the underlying pathophysiological mechanisms remain unclear.Investigating the shared mechanisms and metabolic alterations in these distinct organs will provide valuable insights for clinical therapy.A strong correlation has been identified between the spatiotemporal accumulation patterns of neomycin and the specific occurrence of lipid metabolism disorders in these two organs.The primary allocation of neomycin to mitochondria results in a notable escalation in the accumulation of lipid droplets(LDs)and more interactions between mitochondria and LDs,leading to a sequence of disturbances in lipid metabolism,such as increased lipid ROS and the blocked transfer of fatty acids from LDs to mitochondria.PGC-1αdeficiency worsens the neomycin-induced disorders in lipid metabolism and intensifies the pathological interactions between mitochondria and LDs,as indicated by the exacerbated disturbance of dynamic LD turnover,increased level of oxidized lipids and decreased use of fatty acids.This investigation provides a fresh perspective on the lipid metabolic dysfunction related to mitochondria-LD interactions in drug-induced ototoxicity and nephrotoxicity,potentially providing novel avenues for intervention strategies.展开更多
Neomycin,a crucial aminoglycoside antibiotic,is primarily biosynthesized by Streptomyces fradiae through fermentation.Its widespread applications encompass disease management in crops,treatment of bacterial infections...Neomycin,a crucial aminoglycoside antibiotic,is primarily biosynthesized by Streptomyces fradiae through fermentation.Its widespread applications encompass disease management in crops,treatment of bacterial infections in respiratory and gastrointestinal tracts,among other domains,leading to substantial market demand.Increasing evidence underscores the pivotal role of transcription factors in microbial metabolic regulation,orchestrating the coordinated expression of multiple genes in specific pathways.This orchestration holds the potential to enhance engineered microbial strains,thereby facilitating the precise and efficient synthesis of neomycin.Leveraging transcriptomic analyses of the wild-type strain SF-1 and the mutation-derived high-yield strain SF-2,this study identified significant variations in the expression levels of seven transcription factors.By constructing recombinant strains overexpressing these seven transcription factors,the optimal factor NecR,influencing neomycin production,was pinpointed.Further,promoter optimization was employed to augment neomycin synthesis.Under shaken flask cultivation conditions,the titer of neomycin B reached 11,546 U/mL,marking a 23%enhancement over the mutation-derived high-yield strain SF-2.The in vivo fluorescence reporter gene characterization using EMSA binding revealed that NecR can bind to the promoter region of neoS,thereby enhancing the transcriptional levels of neoS,subsequently promoting neomycin synthesis.This investigation not only furnishes pivotal insights for the construction of high-yield neomycin-producing strains but also elucidates the central role of transcription factors in microbial metabolic regulation.This revelation is poised to offer novel avenues and strategies in the realm of microbial metabolic engineering,holding promise for significant breakthroughs in antibiotic production and other bioproduct synthesis domains.展开更多
文摘Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the Pub Med database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals(including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agentseither as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions.
基金supported by the project for talent training and development of the China National Center for Food Safety Risk Assessment(523 plan)Natural Science Foundation of Guangdong Province(No.2014A030310289 and No.2016A020210055)+1 种基金Natural Science Foundation of SZU(No.201576)National Natural Science Foundation of China(No.21107104)
文摘Immunoassays greatly contribute to veterinary drug residue analysis. However, there are few reports on detecting neomycin residues by immunoassay. Here, a rapid and sensitive chemiluminescent enzyme immunoassay （CLIEA） was successfully developed for neomycin residue analysis. CLIEA demonstrated good cross-reactivity for neomycin, and the IC50 value was 2.4 ng/mL in buffer.
文摘A simple, fast and reliable method, using high performance anion chromatography with pulsed amperometric detection, had been developed for the analysis of neomycin in water samples. The elution and separation were carried out with an isocratic mobile phase, containing 10 mmol/L NaOH. The influence of the concentration and pH of the mobile phase on the separation and detection was investigated. A quadruple-potential waveform used for the detection was optimized. The detection limit of neomycin was down to 0.027 μg/mL. The linearity of neomycin calibration curve ranged from 0.050 to 0.505 μg/mL with correlation coefficient of 0.9997. R.S.D. (n = 11) was 4.0%.
文摘Objective The role of selective decontamination with oral antibiotics(OABs)and mechanical bowel preparation(MBP)prior to elective colorectal surgery is still widely debated.The objective of this study was to compare the outcomes of selective decontamination with neomycin,metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation.Methods Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital,a major Australian tertiary referral hospital,between June 2017 and January 2023.Comparisons between short-term outcomes of OAB+MBP and MBP/no preparation were made using prospectively collected data on length of stay(LOS),readmission,mortality within 30 days,anastomotic leakage(AL),surgical site infection(SSI),urinary tract infection,deep venous thrombosis and/or pulmonary embolism,pneumonia,and ileus.Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery.The Mann-Whitney U test was used to analyse continuous data,and the chi-square test was used for categorical data.Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL.Results Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI(2.7%vs.7.6%,p=0.043)and overall complications(32.7%vs.44.6%,p=0.020),particularly Clavien-Dindo 1 complications(7.3%vs.16.5%,p=0.009).However,the differences in AL(2.7%vs.4.5%,p=0.369)and organ/space SSI(1.3%vs.3.7%,p=0.327)were not statistically significant.The median LOS(6 d vs.6 d,p=0.370)was not different between the groups.Conclusion Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications.There was a trend to toward a lower AL,but this difference was not statistically significant.
文摘Objective: Mastitis is one of the most costly diseases in dairy cows, which greatly decreases milk production. Use of antibiotics in cattle leads to antibiotic-resistance of mastitis-causing bacteria. The present study aimed to investigate synergistic effect of silver nanoparticles (AgNPs) with neomycin or gentamicin antibiotic on mastitis-causing Staphylococcus aureus. Materials and Methods: In this study, 46 samples of milk were taken from the cows with clinical and subclinical mastitis during the august-October 2015 sampling period. In addition to biochemical tests, nuc gene amplification by PCR was used to identify strains of Staphylococcus aureus. Disk diffusion test and microdilution were performed to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional Inhibitory Concentration (FIC) index was calculated to determine the interaction between a combination of AgNPs and each one of the antibiotics. Results: Twenty strains of Staphylococcus aureus were isolated from 46 milk samples and were confirmed by PCR. Based on disk diffusion test, 35%, 10% and 55% of the strains were respectively susceptible, moderately susceptible and resistant to gentamicin. In addition, 35%, 15% and 50% of the strains were respectively susceptible, moderately susceptible and resistant to neomycin. According to FIC index, gentamicin antibiotic and AgNPs had synergistic effects in 50% of the strains. Furthermore, neomycin antibiotic and AgNPs had synergistic effects in 45% of the strains. Conclusion: It could be concluded that a combination of AgNPs with either gentamicin or neomycin showed synergistic antibacterial properties in Staphylococcus aureus isolates from mastitis. In addition, some hypotheses were proposed to explain antimicrobial mechanism of the combination.
文摘Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 169 patients presenting with clinical criteria for vaginitis were included in an open, multicenter trial. Vaginal samples were taken for microbiological analyses and a triple-combination product of nystatin, neomycin and polymyxin B was then started as local treatment, without waiting for the test results. The treatment was continued with the usual dosage (1 vaginal capsule at bedtime for 12 days) for vaginal infections in the scope of the combination product with approved labeling. A second vaginal sample was performed at the end of the treatment. The main efficacy criterion was the clinical success rate (cure or improvement of the clinical signs and symptoms) according to the investigator.Results: 93 patients were included in the efficacy population. Non-exclusively fungal vaginitis (strictly bacterial or bacterial + fungal) represented 31.2% of the cases. The clinical success rate was 97.8% according to the investigator and 95.7% according to the patients. The microbiological success rate was 81.3%, with no differences between etiologies (Candida spp., bacteria or both). The combination product was well-tolerated, despite the local inflammation before treatment. Discussion and conclusion: Given the etiological diversity of vaginitis, this trial supports the efficacy of a triple-combination product (nystatin, neomycin, polymyxin B) as a first-line local treatment of Candida, bacterial or mixed vaginitis.
基金funded in part by the Ministry of Science and Technology of China(2015CB150600)the National Natural Science Foundation of China(31370095 and 31522001)
文摘Neomycins are a group of aminoglycoside antibiotics with both clinical and agricultural applications.To elucidate the regulatory mechanism of neomycin biosynthesis,we completed draft genome sequencing of a neomycin producer Streptomyces fradiae CGMCC 4.7387 from marine sediments,and the neomycin biosynthesis gene cluster was identified.Inactivation of the afsA-g gene encoding a γ-butyrolactone(GBL) synthase in S.fradiae CGMCC 4.7387 resulted in a significant decrease of neomycin production.Quantitative RT-PCR analysis revealed that the transcriptional level of neoR and the aphA-neoGH operon were reduced in the afsA-g::aac(3)Ⅳ mutant.Interestingly,a conserved binding site of AdpA,a key activator in the GBL regulatory cascade,was discovered upstream of neoR,a putative regulatory gene encoding a protein with an ATPase domain and a tetratricopeptide repeat domain.When neoR was inactivated,the neomycin production was reduced about 40%in comparison with the WT strain.Quantitative RT-PCR analysis revealed that the transcriptional levels of genes in the aphA-neoGH operon were reduced clearly in the neoR::aac(3)Ⅳ mutant.Finally,the titers of neomycin were improved considerably by overexpression of qfsA-gand neoR in S.fradiae CGMCC 4.7387.
基金This work was supported by the Earmarked Fund for China Agriculture Research System(grant number CARS-45-19).The authors report no conflicts of interest in this paper.
文摘Neomycin belongs to the family of 2-deoxystreptamine-containing aminoglycoside antibiotics.It is widely used for bacterial infections,targeting most gram-negative and some gram-positive bacteria.Neomycin has also been reported to show antiviral activity.Here,we evaluated the toxicity of neomycin sulfate,and investigated its effect on non-specific immunity and viral infection in crucian carp(Carassius auratus gibelio).The safe concentration of neomycin sulfate for crucian carp was determined to be 102.9 mg/kg in vivo.In oxidative damage assays,neomycin sulfate increased superoxide dismutase and catalase activity and decreased malondialdehyde in the liver of crucian carp.In non-specific blood immune assays,the white blood cell count and complement 3 content significantly increased after neomycin sulfate treatment,while no significant changes were observed in antibacterial or lysozyme activity.In a challenge test,neomycin sulfate protected the crucian carp from cyprinid herpesvirus 2(CyHV-2)infection and inhibited CyHV-2 replication.In cytotoxicity assays,low concentrations of neomycin sulfate had no cytotoxicity on cells from the fins of crucian carp.The results of the present study indicate that oral administration of neomycin sulfate reduced oxidative damage,enhanced immunity and provided protection against CyHV-2 in crucian carp.
基金supported by the National Natural Science Foundation of China(82274014,82330033,82030029,92149304,82101228)the Leading Technology Foundation Research Project of Jiangsu Province(BK20192005,China)+1 种基金National Key R&D Program of China(Nos.2021YFA1101300,2021YFA1101800,and 2020YFA0112503)the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202302,China).
文摘Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics(gentamicin,amikacin,neomycin)and platinum anti-tumor drugs(cisplatin,carboplatin).The inner ear and kidney share similarities in drug deposition and toxicity,but the underlying pathophysiological mechanisms remain unclear.Investigating the shared mechanisms and metabolic alterations in these distinct organs will provide valuable insights for clinical therapy.A strong correlation has been identified between the spatiotemporal accumulation patterns of neomycin and the specific occurrence of lipid metabolism disorders in these two organs.The primary allocation of neomycin to mitochondria results in a notable escalation in the accumulation of lipid droplets(LDs)and more interactions between mitochondria and LDs,leading to a sequence of disturbances in lipid metabolism,such as increased lipid ROS and the blocked transfer of fatty acids from LDs to mitochondria.PGC-1αdeficiency worsens the neomycin-induced disorders in lipid metabolism and intensifies the pathological interactions between mitochondria and LDs,as indicated by the exacerbated disturbance of dynamic LD turnover,increased level of oxidized lipids and decreased use of fatty acids.This investigation provides a fresh perspective on the lipid metabolic dysfunction related to mitochondria-LD interactions in drug-induced ototoxicity and nephrotoxicity,potentially providing novel avenues for intervention strategies.
基金financially supported by National Natural Science Foundations of China(No.32300059)Key research and development projects and achievement transformation projects of Wuhu(Grant No.2023YF096)+1 种基金Scientific Research Start-up Fund for Introduced Talents of Anhui Polytechnic University(2022YOO068)Natural Science Research Project of Colleges and Universities in Anhui Province(Grant 2022AH050971)。
文摘Neomycin,a crucial aminoglycoside antibiotic,is primarily biosynthesized by Streptomyces fradiae through fermentation.Its widespread applications encompass disease management in crops,treatment of bacterial infections in respiratory and gastrointestinal tracts,among other domains,leading to substantial market demand.Increasing evidence underscores the pivotal role of transcription factors in microbial metabolic regulation,orchestrating the coordinated expression of multiple genes in specific pathways.This orchestration holds the potential to enhance engineered microbial strains,thereby facilitating the precise and efficient synthesis of neomycin.Leveraging transcriptomic analyses of the wild-type strain SF-1 and the mutation-derived high-yield strain SF-2,this study identified significant variations in the expression levels of seven transcription factors.By constructing recombinant strains overexpressing these seven transcription factors,the optimal factor NecR,influencing neomycin production,was pinpointed.Further,promoter optimization was employed to augment neomycin synthesis.Under shaken flask cultivation conditions,the titer of neomycin B reached 11,546 U/mL,marking a 23%enhancement over the mutation-derived high-yield strain SF-2.The in vivo fluorescence reporter gene characterization using EMSA binding revealed that NecR can bind to the promoter region of neoS,thereby enhancing the transcriptional levels of neoS,subsequently promoting neomycin synthesis.This investigation not only furnishes pivotal insights for the construction of high-yield neomycin-producing strains but also elucidates the central role of transcription factors in microbial metabolic regulation.This revelation is poised to offer novel avenues and strategies in the realm of microbial metabolic engineering,holding promise for significant breakthroughs in antibiotic production and other bioproduct synthesis domains.
