[Objectives]To investigate the potential applications and mechanisms of action of medicinal plants as bacteriostatic agents,utilizing snow lotus as a case study through network pharmacology.[Methods]The TCMSP and HIT ...[Objectives]To investigate the potential applications and mechanisms of action of medicinal plants as bacteriostatic agents,utilizing snow lotus as a case study through network pharmacology.[Methods]The TCMSP and HIT 2.0 databases were employed to screen and obtain the active components and corresponding targets of snow lotus.The identified targets were subsequently intersected with the antibacterial and bacteriostatic targets sourced from the GeneCards and OMIM databases,resulting in the identification of the antibacterial and bacteriostatic targets associated with snow lotus.Cytoscape software was employed to construct the network diagram illustrating the active components and their corresponding action targets for snow lotus,as well as to analyze the network s topology.Additionally,GO enrichment analysis of the action targets was conducted utilizing the DAVID database.[Results]A total of 12 active components of snow lotus were identified through screening,which corresponded to 294 action targets.Subsequent analysis revealed 117 core action targets of snow lotus that exhibit antibacterial and bacteriostatic properties.The results from the network diagram suggested that snow lotus may exert its antibacterial and bacteriostatic effects through active components such as quercetin,apigenin,and luteolin.Additionally,it appeared to activate the immunomodulatory functions of the human body by interacting with targets such as CASP3,TNF,and IL-6.[Conclusions]Snow lotus may demonstrate antibacterial and bacteriostatic properties through mechanisms of action that involve multiple components,targets,and pathways,from in vivo and in vitro multiple pathways.The integration of botanical bacteriostatic agents with chemical disinfectants that possess broad-spectrum bactericidal effects is advantageous for broadening the bactericidal spectrum and minimizing irritation,in order to facilitate the development of more environmentally friendly and low-toxicity disinfection and bacteriostatic products.展开更多
[Objective] The aim was to explore the effects of seven kinds of Chinese herbal medicine on Escherichia coil and Staphylococcus aureus in terms of unilater- al bacteriostatic effect, such as root and leaf of Ophiopogo...[Objective] The aim was to explore the effects of seven kinds of Chinese herbal medicine on Escherichia coil and Staphylococcus aureus in terms of unilater- al bacteriostatic effect, such as root and leaf of Ophiopogon japonicus, honeycomb, Panax pseudoginseng, and Allium macrostemon. [Method] Herbal active ingredients were extracted by water boiling method and a bacteriostatic experiment was per- formed by oxford cup diffusion method, to select Chinese herbs with antibacterial effects. MIC values of seven kinds of Chinese herbal medicine were determined by in vitro half-fold dilution method. [Results] Root and leaf of Ophiopogon japonicus, honeycomb, Panax pseudoginseng, Allium macrostemon, Juncus effusus and Xanthi- um sibiricum had bacteriostatic effects on Escherichia coil and Staphylococcus au- reus in varying degrees. Xanthium and leaf of Ophiopogon japonicus performed bet- ter on Escherichia coil, with MIC values at 7.81 and 15.63 mg/ml, respectively. Panax pseudoginseng and Xanthium performed better on Staphylococcus aureus with MIC values at 15.63 and 31.25 mg/ml. And the drug＇s effect was positively correlated with the concentration. [Conclusion] Xanthium sibiricum is the best bacte- riostatic effect, followed by leaf of Ophiopogon japonicus, and Juncus effusus per- forms the poorest. Panax pseudoginseng showed the best bacteriostatic effect, fol- lowed by Xanthium sibiricum and Juncus effusus performs the poorest. These pro- vide references for clinic safety.展开更多
[Objective] The effect of bacteriostat （Qianxing No.l） on open tissue cul- ture of sugarca6e was discussed in this paper. [Method] The axillary bud explants of Qiantang No.5 were used as experimental material. Diffe...[Objective] The effect of bacteriostat （Qianxing No.l） on open tissue cul- ture of sugarca6e was discussed in this paper. [Method] The axillary bud explants of Qiantang No.5 were used as experimental material. Different concentrations of Qianxing No.1 were added in the media to determine the optimal bacteriostatic con- centrations of Qianxing No.1 for induction and proliferation culture of sugarcane in the open tissue culture. [Result] The results showed Qianxing No.1 with the con- centration of 0.5% could effectively inhibit the medium contamination. Under that bacteriostatic concentration, the surviving rate of explants was up to 80%, and the propagation coefficient was 3.1. [Conclusion] This research would provide a theoretic basis for the simplification of sugarcane tissue culture procedure and the reduction of production costs.展开更多
Lactic acid bacteria(LAB)are a representative probiotic.As the dominant flora in the human intestinal tract,LAB can regulate the balance of human intestinal flora and improve host health.The purpose of this study was ...Lactic acid bacteria(LAB)are a representative probiotic.As the dominant flora in the human intestinal tract,LAB can regulate the balance of human intestinal flora and improve host health.The purpose of this study was to isolate and screen LAB that are well suited to the intestinal characteristics of the Chinese population,with excellent probiotics and high antibacterial activity.After 16S ribosomal RNA(rRNA)homology and phylogenetic tree analysis,potential probiotics were tested for their antibacterial activity,resistance to artificial gastrointestinal fluid and drugs,surface hydrophobicity,and safety.Three strains of LAB with acid resistance,bile salt resistance,epithelial cell adhesion,and no multidrug resistance were selected:Lactobacillus salivarius,Leuconostoc lactis,and Lactobacillus paracasei.Analysis of the antibacterial active substances in the three strains and their fermentation broths revealed that the main antibacterial substances of L.lactis were organic acids,whereas those of L.salivarius and L.paracasei were organic acids and bacteriocins with broad-spectrum antibacterial activity.These three strains of probiotic LAB with high antibacterial activity were identified as bacterial resources that could potentially be used to develop probiotic preparations for the prevention and treatment of intestinal diseases caused by intestinal pathogens.展开更多
[ Objective] To investigate the in vitro bacteriostatic activity of Chinese herbal medicines （ rhubarb, Baikal skullcap root, honeysuckle, eucommia bark and Chinese date） and their compounds against two common patho...[ Objective] To investigate the in vitro bacteriostatic activity of Chinese herbal medicines （ rhubarb, Baikal skullcap root, honeysuckle, eucommia bark and Chinese date） and their compounds against two common pathogens of Scylla serrata （ Vibrio parahaemolyticus and Aeromonas hydrophila）. [Method] Drug sensitivity of the bacteria was determined by paper method. Minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） were determined by dilution method and plate method, respectively. [Result] The bacteriostatic order of single medicines on V. parahaemolyticus were Baikal skullcap root 〉 honeysuckle 〉 rhubarb 〉 Chinese date 〉 eucommia bark. The bacteriostatic order of the compounds were A =B = C 〉 D. Among these medicines, the Baikal skullcap root and the compounds A, B, C and D had better bactericidal effects on V. parahaemolyticus. The bacteriostatic order of single medicines on A. hydrophila was rhubarb 〉 Baikal skullcap root 〉 honeysuckle 〉 Chinese date 〉 eucommia bark. The bacteriostatic order of the compounds were A 〉 B 〉 C = D, while the rhubarb and the compound C had better bactericidal effects on A. hydrophila. [ Conclusion] The Chinese herbal medicines including rhubarb, Baikal skullcap root, honeysuckle, eucommia bark and Chinese date have good bacteriostatic effects on V. parahaemolyticus and A. hydrophila, and they can be used to treat bacterial infection in Scylla serrata.展开更多
Pectobacterium chrysanthemi is one of the main pathogens of soft rot disease of Amorphophallus konjac.The bacteriostatic effect of extracts from 10 kinds of traditional Chinese medicine and garlic on Pectobacterium ch...Pectobacterium chrysanthemi is one of the main pathogens of soft rot disease of Amorphophallus konjac.The bacteriostatic effect of extracts from 10 kinds of traditional Chinese medicine and garlic on Pectobacterium chrysanthemi was studied in this experiment.The results showed that the extracts of Coptis chinensis,garlic,Scutellaria baicalensis,Mume Fructus and Bupleurum had significant bacteriostatic effect.Among them,Coptis chinensis and garlic had the best bacteriostatic effect on Pectobacterium chrysanthemi,and the diameter of inhibition zone was 2.27 and 2.19 cm,respectively,followed by Scutellaria baicalensis,with the diameter of inhibition zone of 1.68 cm.The extracts of Coptis chinensis,Scutellaria baicalensis and garlic with good bacteriostatic effect were diluted by double dilution method,and the bacteriostatic effect was determined.The results showed that 2-fold dilution of Coptis chinensis and 2-fold and 4-fold dilution of Scutellaria baicalensis had significant bacteriostatic effect,but the bacteriostatic effect of garlic extract was not obvious after dilution.展开更多
Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstl...Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstly evaluated the growth inhibition effect of HA/CMC for E. coli and S. aureus by determining the optical density (OD)650 in the incubation medium. At second, to determine the viable counts of bacteria, total adenosine triphosphate (ATP) were measured with five groups;several concentrations of HA/CMC and control. Results: OD curve gradually elevated and reached to plateau at 4 hours in E. coli. and 6 hours in S. aureus. After reaching plateau, the growth inhibition of both strains was statistically significantly correlated to the concentrations of HA/CMC. The ATP productions had statistically significant differences at 6 hours after incubation and inhibited in dose-dependence of a well-dissolved HA/CMC. Conclusion: HA/CMC may have dose-dependently bacteriostatic effects on S. aureus and E. coli.展开更多
Piroctone olamine(OCT) was used as the main bacteriostatic component, the inhibition of OCT in different kinds and mass concentrations of surfactants were studied. Six surfactants commonly used in personal care produc...Piroctone olamine(OCT) was used as the main bacteriostatic component, the inhibition of OCT in different kinds and mass concentrations of surfactants were studied. Six surfactants commonly used in personal care products, i.e. sodium laureth sulfate(AES), cocamidopropyl betaine(CAB 35), sodium lauroyl sarcosinate(LS-30), sodium lauroyl glutamate(ULS-30S), alkyl glycoside(APG), cocamide methyl MEA(CMMEA),were used. The results showed that the bacteriostatic of OCT decreased with the increase of AES, which was suggested ≤ 5%. OCT has good bacteriostatic performance in the systems of amino acid surfactants and high dosage of amphoteric surfactants, 5% LS 30 and ≥ 10% CAB 35 was recommended. High dosage of nonionic surfactant could interfere the bacteriostatic performance of OCT, the recommended dosage was ≤ 2%.In addition, OCT has good bacteriostatic performance against Staphylococcus aureus, Escherichia coli and Candida albicans when pH was controlled less than 5.5.展开更多
Bacteriostatic laundry detergent was prepared with application of dodecyl dimethyl benzyl ammonium chloride (1227). In accordance with relevant standards applied in Chinese detergent industry, the effect of 1227 on se...Bacteriostatic laundry detergent was prepared with application of dodecyl dimethyl benzyl ammonium chloride (1227). In accordance with relevant standards applied in Chinese detergent industry, the effect of 1227 on sensory and physiochemical quality indices, detergency and foaming performance of laundry detergent were comprehensively investigated,and antimicrobial performance as well as practical application performance including skin irritation of laundry detergent formulated with 1227 was emphatically examined and compared with that of market product with similar functions. Results indicated that, in formulation without anionic surfactant, all indices of self-prepared bacteriostatic laundry detergent can meet requirements specified in relevant standards. The foaming power of self-prepared bacteriostatic laundry detergent was lower and easier to rinse than bacteriostatic laundry detergent product in market. Using aqueous solution of 1% mass fraction of self-prepared bacteriostatic laundry detergent containing 2%of 1227, the antibacterial rate for 20 min on both Escherichia coli and Staphylococcus aureus separately reached 100%, which was much better than that of the bacteriostatic laundry detergent product from market. The action effectiveness of the self-prepared bacteriostatic laundry detergent can be maintained for a longer time period and shows no obvious irritation effect to human skin.展开更多
Antibiotics combat bacteria through their bacteriostatic(by growth inhibition)or bactericidal(by killing bacteria)action.Mechanistically,it has been proposed that bactericidal antibiotics trigger cellular damage,while...Antibiotics combat bacteria through their bacteriostatic(by growth inhibition)or bactericidal(by killing bacteria)action.Mechanistically,it has been proposed that bactericidal antibiotics trigger cellular damage,while bacteriostatic antibiotics suppress cellular metabolism.Here,we demonstrate how the difference between bacteriostatic and bactericidal activities of the antibiotic chloramphenicol can be attributed to an antibiotic-induced bacterial protective response:the stringent response.Chloramphenicol targets the ribosome to inhibit the growth of the Gram-positive bacterium Bacillus subtilis.Intriguingly,we found that chloramphenicol becomes bactericidal in B.subtilis mutants unable to produce(p)ppGpp.We observed a similar(p)ppGpp-dependent bactericidal effect of chloramphenicol in the Gram-positive pathogen Enterococcus faecalis.In B.subtilis,chloramphenicol treatment induces(p)ppGpp accumulation through the action of the(p)ppGpp synthetase RelA.(p)ppGpp subsequently depletes the intracellular concentration of GTP and antagonizes GTP action.This GTP regulation is critical for preventing chloramphenicol from killing B.subtilis,as bypassing(p)ppGpp-dependent GTP regulation potentiates chloramphenicol killing,while reducing GTP synthesis increases survival.Finally,chloramphenicol treatment protects cells from the classical bactericidal antibiotic vancomycin,reminiscent of the clinical phenomenon of antibiotic antagonism.Taken together,our findings suggest a role of(p)ppGpp in the control of the bacteriostatic and bactericidal activity of antibiotics in Gram-positive bacteria,which can be exploited to potentiate the efficacy of existing antibiotics.展开更多
基金Supported by Shanghai Putuo District Science and Technology R&D Platform Project(2024QX04).
文摘[Objectives]To investigate the potential applications and mechanisms of action of medicinal plants as bacteriostatic agents,utilizing snow lotus as a case study through network pharmacology.[Methods]The TCMSP and HIT 2.0 databases were employed to screen and obtain the active components and corresponding targets of snow lotus.The identified targets were subsequently intersected with the antibacterial and bacteriostatic targets sourced from the GeneCards and OMIM databases,resulting in the identification of the antibacterial and bacteriostatic targets associated with snow lotus.Cytoscape software was employed to construct the network diagram illustrating the active components and their corresponding action targets for snow lotus,as well as to analyze the network s topology.Additionally,GO enrichment analysis of the action targets was conducted utilizing the DAVID database.[Results]A total of 12 active components of snow lotus were identified through screening,which corresponded to 294 action targets.Subsequent analysis revealed 117 core action targets of snow lotus that exhibit antibacterial and bacteriostatic properties.The results from the network diagram suggested that snow lotus may exert its antibacterial and bacteriostatic effects through active components such as quercetin,apigenin,and luteolin.Additionally,it appeared to activate the immunomodulatory functions of the human body by interacting with targets such as CASP3,TNF,and IL-6.[Conclusions]Snow lotus may demonstrate antibacterial and bacteriostatic properties through mechanisms of action that involve multiple components,targets,and pathways,from in vivo and in vitro multiple pathways.The integration of botanical bacteriostatic agents with chemical disinfectants that possess broad-spectrum bactericidal effects is advantageous for broadening the bactericidal spectrum and minimizing irritation,in order to facilitate the development of more environmentally friendly and low-toxicity disinfection and bacteriostatic products.
文摘[Objective] The aim was to explore the effects of seven kinds of Chinese herbal medicine on Escherichia coil and Staphylococcus aureus in terms of unilater- al bacteriostatic effect, such as root and leaf of Ophiopogon japonicus, honeycomb, Panax pseudoginseng, and Allium macrostemon. [Method] Herbal active ingredients were extracted by water boiling method and a bacteriostatic experiment was per- formed by oxford cup diffusion method, to select Chinese herbs with antibacterial effects. MIC values of seven kinds of Chinese herbal medicine were determined by in vitro half-fold dilution method. [Results] Root and leaf of Ophiopogon japonicus, honeycomb, Panax pseudoginseng, Allium macrostemon, Juncus effusus and Xanthi- um sibiricum had bacteriostatic effects on Escherichia coil and Staphylococcus au- reus in varying degrees. Xanthium and leaf of Ophiopogon japonicus performed bet- ter on Escherichia coil, with MIC values at 7.81 and 15.63 mg/ml, respectively. Panax pseudoginseng and Xanthium performed better on Staphylococcus aureus with MIC values at 15.63 and 31.25 mg/ml. And the drug＇s effect was positively correlated with the concentration. [Conclusion] Xanthium sibiricum is the best bacte- riostatic effect, followed by leaf of Ophiopogon japonicus, and Juncus effusus per- forms the poorest. Panax pseudoginseng showed the best bacteriostatic effect, fol- lowed by Xanthium sibiricum and Juncus effusus performs the poorest. These pro- vide references for clinic safety.
基金Supported by SUT PhD Research FundQian Nong Ke He(Innovation Found)2011012Qian Ke He"NY"[2012]3034~~
文摘[Objective] The effect of bacteriostat （Qianxing No.l） on open tissue cul- ture of sugarca6e was discussed in this paper. [Method] The axillary bud explants of Qiantang No.5 were used as experimental material. Different concentrations of Qianxing No.1 were added in the media to determine the optimal bacteriostatic con- centrations of Qianxing No.1 for induction and proliferation culture of sugarcane in the open tissue culture. [Result] The results showed Qianxing No.1 with the con- centration of 0.5% could effectively inhibit the medium contamination. Under that bacteriostatic concentration, the surviving rate of explants was up to 80%, and the propagation coefficient was 3.1. [Conclusion] This research would provide a theoretic basis for the simplification of sugarcane tissue culture procedure and the reduction of production costs.
基金the National Key Research and Development Program of China(No.2016YFD0400605)。
文摘Lactic acid bacteria(LAB)are a representative probiotic.As the dominant flora in the human intestinal tract,LAB can regulate the balance of human intestinal flora and improve host health.The purpose of this study was to isolate and screen LAB that are well suited to the intestinal characteristics of the Chinese population,with excellent probiotics and high antibacterial activity.After 16S ribosomal RNA(rRNA)homology and phylogenetic tree analysis,potential probiotics were tested for their antibacterial activity,resistance to artificial gastrointestinal fluid and drugs,surface hydrophobicity,and safety.Three strains of LAB with acid resistance,bile salt resistance,epithelial cell adhesion,and no multidrug resistance were selected:Lactobacillus salivarius,Leuconostoc lactis,and Lactobacillus paracasei.Analysis of the antibacterial active substances in the three strains and their fermentation broths revealed that the main antibacterial substances of L.lactis were organic acids,whereas those of L.salivarius and L.paracasei were organic acids and bacteriocins with broad-spectrum antibacterial activity.These three strains of probiotic LAB with high antibacterial activity were identified as bacterial resources that could potentially be used to develop probiotic preparations for the prevention and treatment of intestinal diseases caused by intestinal pathogens.
基金funded by the Transformation Project of Scientific Achievements in Guangdong Colleges (cgzhzd0812)
文摘[ Objective] To investigate the in vitro bacteriostatic activity of Chinese herbal medicines （ rhubarb, Baikal skullcap root, honeysuckle, eucommia bark and Chinese date） and their compounds against two common pathogens of Scylla serrata （ Vibrio parahaemolyticus and Aeromonas hydrophila）. [Method] Drug sensitivity of the bacteria was determined by paper method. Minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） were determined by dilution method and plate method, respectively. [Result] The bacteriostatic order of single medicines on V. parahaemolyticus were Baikal skullcap root 〉 honeysuckle 〉 rhubarb 〉 Chinese date 〉 eucommia bark. The bacteriostatic order of the compounds were A =B = C 〉 D. Among these medicines, the Baikal skullcap root and the compounds A, B, C and D had better bactericidal effects on V. parahaemolyticus. The bacteriostatic order of single medicines on A. hydrophila was rhubarb 〉 Baikal skullcap root 〉 honeysuckle 〉 Chinese date 〉 eucommia bark. The bacteriostatic order of the compounds were A 〉 B 〉 C = D, while the rhubarb and the compound C had better bactericidal effects on A. hydrophila. [ Conclusion] The Chinese herbal medicines including rhubarb, Baikal skullcap root, honeysuckle, eucommia bark and Chinese date have good bacteriostatic effects on V. parahaemolyticus and A. hydrophila, and they can be used to treat bacterial infection in Scylla serrata.
文摘Pectobacterium chrysanthemi is one of the main pathogens of soft rot disease of Amorphophallus konjac.The bacteriostatic effect of extracts from 10 kinds of traditional Chinese medicine and garlic on Pectobacterium chrysanthemi was studied in this experiment.The results showed that the extracts of Coptis chinensis,garlic,Scutellaria baicalensis,Mume Fructus and Bupleurum had significant bacteriostatic effect.Among them,Coptis chinensis and garlic had the best bacteriostatic effect on Pectobacterium chrysanthemi,and the diameter of inhibition zone was 2.27 and 2.19 cm,respectively,followed by Scutellaria baicalensis,with the diameter of inhibition zone of 1.68 cm.The extracts of Coptis chinensis,Scutellaria baicalensis and garlic with good bacteriostatic effect were diluted by double dilution method,and the bacteriostatic effect was determined.The results showed that 2-fold dilution of Coptis chinensis and 2-fold and 4-fold dilution of Scutellaria baicalensis had significant bacteriostatic effect,but the bacteriostatic effect of garlic extract was not obvious after dilution.
文摘Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstly evaluated the growth inhibition effect of HA/CMC for E. coli and S. aureus by determining the optical density (OD)650 in the incubation medium. At second, to determine the viable counts of bacteria, total adenosine triphosphate (ATP) were measured with five groups;several concentrations of HA/CMC and control. Results: OD curve gradually elevated and reached to plateau at 4 hours in E. coli. and 6 hours in S. aureus. After reaching plateau, the growth inhibition of both strains was statistically significantly correlated to the concentrations of HA/CMC. The ATP productions had statistically significant differences at 6 hours after incubation and inhibited in dose-dependence of a well-dissolved HA/CMC. Conclusion: HA/CMC may have dose-dependently bacteriostatic effects on S. aureus and E. coli.
文摘Piroctone olamine(OCT) was used as the main bacteriostatic component, the inhibition of OCT in different kinds and mass concentrations of surfactants were studied. Six surfactants commonly used in personal care products, i.e. sodium laureth sulfate(AES), cocamidopropyl betaine(CAB 35), sodium lauroyl sarcosinate(LS-30), sodium lauroyl glutamate(ULS-30S), alkyl glycoside(APG), cocamide methyl MEA(CMMEA),were used. The results showed that the bacteriostatic of OCT decreased with the increase of AES, which was suggested ≤ 5%. OCT has good bacteriostatic performance in the systems of amino acid surfactants and high dosage of amphoteric surfactants, 5% LS 30 and ≥ 10% CAB 35 was recommended. High dosage of nonionic surfactant could interfere the bacteriostatic performance of OCT, the recommended dosage was ≤ 2%.In addition, OCT has good bacteriostatic performance against Staphylococcus aureus, Escherichia coli and Candida albicans when pH was controlled less than 5.5.
文摘Bacteriostatic laundry detergent was prepared with application of dodecyl dimethyl benzyl ammonium chloride (1227). In accordance with relevant standards applied in Chinese detergent industry, the effect of 1227 on sensory and physiochemical quality indices, detergency and foaming performance of laundry detergent were comprehensively investigated,and antimicrobial performance as well as practical application performance including skin irritation of laundry detergent formulated with 1227 was emphatically examined and compared with that of market product with similar functions. Results indicated that, in formulation without anionic surfactant, all indices of self-prepared bacteriostatic laundry detergent can meet requirements specified in relevant standards. The foaming power of self-prepared bacteriostatic laundry detergent was lower and easier to rinse than bacteriostatic laundry detergent product in market. Using aqueous solution of 1% mass fraction of self-prepared bacteriostatic laundry detergent containing 2%of 1227, the antibacterial rate for 20 min on both Escherichia coli and Staphylococcus aureus separately reached 100%, which was much better than that of the bacteriostatic laundry detergent product from market. The action effectiveness of the self-prepared bacteriostatic laundry detergent can be maintained for a longer time period and shows no obvious irritation effect to human skin.
基金supported,in part,by an R35 GM127088 Grant from NIGMS and a USDA Hatch Formula Grant from Wisconsin Agricultural Experiment Station WIS01740(to Jue D.Wang).
文摘Antibiotics combat bacteria through their bacteriostatic(by growth inhibition)or bactericidal(by killing bacteria)action.Mechanistically,it has been proposed that bactericidal antibiotics trigger cellular damage,while bacteriostatic antibiotics suppress cellular metabolism.Here,we demonstrate how the difference between bacteriostatic and bactericidal activities of the antibiotic chloramphenicol can be attributed to an antibiotic-induced bacterial protective response:the stringent response.Chloramphenicol targets the ribosome to inhibit the growth of the Gram-positive bacterium Bacillus subtilis.Intriguingly,we found that chloramphenicol becomes bactericidal in B.subtilis mutants unable to produce(p)ppGpp.We observed a similar(p)ppGpp-dependent bactericidal effect of chloramphenicol in the Gram-positive pathogen Enterococcus faecalis.In B.subtilis,chloramphenicol treatment induces(p)ppGpp accumulation through the action of the(p)ppGpp synthetase RelA.(p)ppGpp subsequently depletes the intracellular concentration of GTP and antagonizes GTP action.This GTP regulation is critical for preventing chloramphenicol from killing B.subtilis,as bypassing(p)ppGpp-dependent GTP regulation potentiates chloramphenicol killing,while reducing GTP synthesis increases survival.Finally,chloramphenicol treatment protects cells from the classical bactericidal antibiotic vancomycin,reminiscent of the clinical phenomenon of antibiotic antagonism.Taken together,our findings suggest a role of(p)ppGpp in the control of the bacteriostatic and bactericidal activity of antibiotics in Gram-positive bacteria,which can be exploited to potentiate the efficacy of existing antibiotics.
