Biotin(vitamin H or B7)is a sulfur-containing intermediate of fatty acids,and functions as an indispensable co-enzyme across the three domains of life.In general,biotin synthesis occurs in bac-teria,fungi and plants,r...Biotin(vitamin H or B7)is a sulfur-containing intermediate of fatty acids,and functions as an indispensable co-enzyme across the three domains of life.In general,biotin synthesis occurs in bac-teria,fungi and plants,rather than mammals and birds.In certain bacterial pathogens like the tuberculosis-causing agent,Mycobac-terium[1]and the life-threatening causative,Francisella[2],it also acts as a nutritional restriction factor having a critical role in bac-terial pathogenesis.Apart from hypervirulence of the two recalci-trant ESKAPE members,Klebsiella pneumoniae[3]and Pseudomonas aeruginosa[4,5],biotin biosynthesis was recently demonstrated to determine Acinetobacter baumannii polymyxin resistance[6].As an energetically-expansive molecule whose de novo biosynthesis requires 15-20 ATP equivalents,a number of diversified bacteria have evolved different regulated mechanisms for biotin production(perhaps salvage).The bifunctional enzyme BirA of E.coli is a paradigm regulator of biotin synthesis[7].In addition,two distinct regulatory mechanisms are functionally defined.Namely,they include the BioR repressor restricted to a-proteobacte ria[8],and the BioQ regulator found in Corynebac-terium glutamicum and Mycobacterium smegmatis[9].展开更多
Tetracyclines,a group of antimicrobial agents targeting protein synthesis,have been extensively used in agricultural,veterinary,and clinic settings[1].The sporadic rise in tetracycline resistance is partially due to t...Tetracyclines,a group of antimicrobial agents targeting protein synthesis,have been extensively used in agricultural,veterinary,and clinic settings[1].The sporadic rise in tetracycline resistance is partially due to the occurrence of efflux pumps and/or ribosome protection[1,2].The growing body of tetracycline-inactivating enzymes(e.g.,TetX(X1 to X4)[3,4]and Tet(47 to 55)[5])represents an alternative mechanism for tetracycline resistance,and threatens the renewed interest of tigecycline as a last-resort defense against lethal infections with carbapenem-resistant Enterobacteriaceae and Acinetobacter species.展开更多
Dear Editor, The discovery that the mobile colistin resistance gene （mcr-1） is encoded by plasmids and is prevalent in food animals and human beings worldwide （Hasman et al., 2015; Liu et al., 2015） has challenge...Dear Editor, The discovery that the mobile colistin resistance gene （mcr-1） is encoded by plasmids and is prevalent in food animals and human beings worldwide （Hasman et al., 2015; Liu et al., 2015） has challenged greatly our traditional idea that polymyxin （consisting of two isoforms：展开更多
Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram- negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin ...Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram- negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene （mcr-1） is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-l-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-l-positive Escherichia coli （E15004, E15015 and E15017） and define general features through analyses of bacterial comparative genomics. Fur- ther genomic mining together with sequence typing allowed us to elucidate that the MCR-l-carrying E. coli E15017 belongs to the sequence type ST648 and copro- duces extended-spectrum β-1actamase （ESBL）. Given the fact that ST648 has been known to associate New Delhi metallo-β-1actamase 1 or ESBL, with either our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.展开更多
Dear Editor,Emergence of bacteria with multiple drug resistance is a major problem in global public health.Polymyxin comprising polymyxin E（colistin）and polymyxin B is generally recognized as the last-resort antibio...Dear Editor,Emergence of bacteria with multiple drug resistance is a major problem in global public health.Polymyxin comprising polymyxin E（colistin）and polymyxin B is generally recognized as the last-resort antibiotics with broad-spectrum展开更多
An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome ...An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome sequencing revealed 5 unique plasmids, namely pHXH-1, pHXH-2, pHXH-3, pHXH-4 and pHXH- 5）. Among them, pHXHI and pHXH4 encode ESBL, and pHXH-5 mediates MCR-1 colistin resistance. The results indicate that the potentially-national dissemination of MCR-l-positive pathogens with pan-drug resistance proceeds via food chains.展开更多
Dear Editor,Since 2016, a growing number of mobile colistin resistance(mcr) genes have been identified and characterized (Liu et al., 2016). In addition to mcr-1 and its variants, mcr-2 to mcr-8 have now been reported...Dear Editor,Since 2016, a growing number of mobile colistin resistance(mcr) genes have been identified and characterized (Liu et al., 2016). In addition to mcr-1 and its variants, mcr-2 to mcr-8 have now been reported, which reflects a significant threat to public health and agricultural production (Sun et al.,2018).展开更多
The Escherichia coil fadR protein product, a paradigm/ prototypical FadR regulator, positively regulates fabA and fabB, the two critical genes for unsaturated fatty acid （UFA） biosynthesis. However the scenario in t...The Escherichia coil fadR protein product, a paradigm/ prototypical FadR regulator, positively regulates fabA and fabB, the two critical genes for unsaturated fatty acid （UFA） biosynthesis. However the scenario in the other γ- proteobacteria, such as Shewanella with the marine ori- gin, is unusual in that Rodionov and coworkers predicted that only fabA （not fabB） has a binding site for FadR pro- tein. It raised the possibility of fad regulon contraction. Here we report that this is the case. Sequence alignment of the FadR homologs revealed that the N-terminal DNA- binding domain exhibited remarkable similarity, whereas the ligand-accepting motif at C-terminus is relatively-less conserved. The FadR homologue of S. oneidensis （re- ferred to FadR_she） was over-expressed and purified to homogeneity. Integrative evidence obtained by FPLC （fast protein liquid chromatography） and chemical cross. linking analyses elucidated that FadR_she protein can dimerize in solution, whose identity was determined by MALDI-TOF-MS. In vitro data from electrophoretic mobil. ity shift assays suggested that FadR_she is almost functionally-exchangeable/equivalent to E. coil FadR （FadR_ec） in the ability of binding the E. coil fabA （and fabB） promoters. In an agreement with that of E. coil fabA, S. oneidensis fabA promoter bound both FadR_she andFadR_ec, and was disassociated specifically with the FadR regulatory protein upon the addition of long-chain acyI-CoA thioesters. To monitor in vivo effect exerted by FadR on Shewanella fabA expression, the native pro- moter of S. oneidensis fabA was fused to a LacZ reporter gene to engineer a chromosome fabA-lacZtranscriptional fusion in E. coil. As anticipated, the removal of fadR gene gave about 2-fold decrement of Shewanella fabA expression by β-gal activity, which is almost identical to the inhibitory level by the addition of oleate. Therefore, we concluded that fabA is contracted to be the only one member of fad regulon in the context of fatty acid syn- thesis in the marine bacteria Shewanella genus.展开更多
Zika virus （ZIKV） is a previously-neglected, but newly-emerging zoonotic pathogen that has swept most of the western hemisphere. The unexpected attention aroused worldwide lies in the explosive spread of ZIKV to Bra...Zika virus （ZIKV） is a previously-neglected, but newly-emerging zoonotic pathogen that has swept most of the western hemisphere. The unexpected attention aroused worldwide lies in the explosive spread of ZIKV to Brazil and USA in 2015 and its rare correlation to micro- cephaly in newborns, raising a serious challenge to public health. We show the origin and fast dissemination of these epidemic ZIKA isolates. Phylogenetic analyses revealed that all the newly-emerging ZIKV isolates belong to the Asian-American Lineage. Structural analyses of the ZIKV E surface protein suggested that it might adopt a similar entry mechanism to that of other Flavi-viruses like Dengue Virus and West Nile Virus.展开更多
Fatty acids (FAs) are building blocks required for the threedomains of life. The machinery of type II fatty acid synthesis is longrecognized as a druggable pathway against deadly infections withdrug-resistant bacteria...Fatty acids (FAs) are building blocks required for the threedomains of life. The machinery of type II fatty acid synthesis is longrecognized as a druggable pathway against deadly infections withdrug-resistant bacterial pathogens [1]. However, an everincreasing body of exogenous FAs (eFA) utilization routes posesthe possibility of replacing bacterial de novo FA synthesis, whichmight compromise the FAS II-directed antimicrobials, like cerulenin[2–4]. As for Gram-negative species, the paradigm executorof an eFA recycling denotes an acyl-ACP synthetase (AasS) of thezoonotic pathogen Vibrio harveyi [5]. In contrast, a unique twocomponent system of fatty acid kinase called FakA/B [6], is exclusively present in Staphylococcus and Enterococcus/Streptococcus,two important lineages of Gram-positive bacterium (Fig. S1a, bonline) [6,7].展开更多
Antimicrobial resistance(AMR)is one of the top global challenges of public health concern.In 2019,it was estimated that AMR claimed around 5 million deaths worldwide[1].Pseudomonas aeruginosa,which originated in soil ...Antimicrobial resistance(AMR)is one of the top global challenges of public health concern.In 2019,it was estimated that AMR claimed around 5 million deaths worldwide[1].Pseudomonas aeruginosa,which originated in soil and water,is recognized as an opportunistic pathogen causing recalcitrant infections.Carbapenem-resistant P.aeruginosa(CRPA)is listed by the World Health Organization(WHO)as an important member of top priority“ESKAPE”pathogens.This is largely supported by the fact that in 2020,CRPA had caused28,8000 nosocomial infections with about 2500 deaths.Apart from porin mutations,the acquisition of Klebsiella pneumoniae carbapenemase(termed as KPC-2)constitutes an alternative mechanism for carbapenem resistance in P.aeruginosa,which compromises the clinical efficacy of the carbapenem as a“last resort”option.Notably,the transferability of blaKPC-2 determinants facilitates global dissemination of CRPA in the context of“one health”consisting of humans,animals,plants/crops,and environmental settings.In addition to antimicrobial stewardship,coordinated global action is necessary to mitigate AMR progression.展开更多
Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have re...Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase （Ga5DH） in cell division of the zoonotic pathogen Strepto- coccus suis. GaSDH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the conse- quence of Ga5DH deprivation in S. suis causing FtsZ delo- calization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that GaSDH may function to prevent the formation of ectopic Z rings during S. suis cell division.展开更多
基金supported by the National Key R&D Program of China(2023YFC2308403)the National Science Fund for Distin-guished Young Scholars(32125003)the National Natural Science Foundation of China(32141001).
文摘Biotin(vitamin H or B7)is a sulfur-containing intermediate of fatty acids,and functions as an indispensable co-enzyme across the three domains of life.In general,biotin synthesis occurs in bac-teria,fungi and plants,rather than mammals and birds.In certain bacterial pathogens like the tuberculosis-causing agent,Mycobac-terium[1]and the life-threatening causative,Francisella[2],it also acts as a nutritional restriction factor having a critical role in bac-terial pathogenesis.Apart from hypervirulence of the two recalci-trant ESKAPE members,Klebsiella pneumoniae[3]and Pseudomonas aeruginosa[4,5],biotin biosynthesis was recently demonstrated to determine Acinetobacter baumannii polymyxin resistance[6].As an energetically-expansive molecule whose de novo biosynthesis requires 15-20 ATP equivalents,a number of diversified bacteria have evolved different regulated mechanisms for biotin production(perhaps salvage).The bifunctional enzyme BirA of E.coli is a paradigm regulator of biotin synthesis[7].In addition,two distinct regulatory mechanisms are functionally defined.Namely,they include the BioR repressor restricted to a-proteobacte ria[8],and the BioQ regulator found in Corynebac-terium glutamicum and Mycobacterium smegmatis[9].
基金supported by National Key R&D Program of China(2017YFD0500202,YF)National Natural Science Foundation of China(31830001,31570027&81772142,YF)
文摘Tetracyclines,a group of antimicrobial agents targeting protein synthesis,have been extensively used in agricultural,veterinary,and clinic settings[1].The sporadic rise in tetracycline resistance is partially due to the occurrence of efflux pumps and/or ribosome protection[1,2].The growing body of tetracycline-inactivating enzymes(e.g.,TetX(X1 to X4)[3,4]and Tet(47 to 55)[5])represents an alternative mechanism for tetracycline resistance,and threatens the renewed interest of tigecycline as a last-resort defense against lethal infections with carbapenem-resistant Enterobacteriaceae and Acinetobacter species.
基金supported by Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars (LR15H190001)the National Natural Science Foundation of China (31570027)+1 种基金the start-up package from Zhejiang University (Youjun Feng)the "Young 1000 Talents" Award (Youjun Feng)
文摘Dear Editor, The discovery that the mobile colistin resistance gene （mcr-1） is encoded by plasmids and is prevalent in food animals and human beings worldwide （Hasman et al., 2015; Liu et al., 2015） has challenged greatly our traditional idea that polymyxin （consisting of two isoforms：
基金This work was supported by Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars （LR15H190001）, the National Natural Science Foundation of China （31570027）, and a start-up package from Zhejiang University （Y.F.）. Dr. Feng is a recipient of the ＂Young 1000 Talents＂ Award.
文摘Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram- negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene （mcr-1） is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-l-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-l-positive Escherichia coli （E15004, E15015 and E15017） and define general features through analyses of bacterial comparative genomics. Fur- ther genomic mining together with sequence typing allowed us to elucidate that the MCR-l-carrying E. coli E15017 belongs to the sequence type ST648 and copro- duces extended-spectrum β-1actamase （ESBL）. Given the fact that ST648 has been known to associate New Delhi metallo-β-1actamase 1 or ESBL, with either our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.
基金supported by the National Basic Research Program of China(2016YFC1200100)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(LR15H-190001)+2 种基金the National Natural Science Foundation of China(31570027)the start-up package from Zhejiang University(Youjun Feng)Dr.Feng is a recipient of the"Young 1000 Talents"Award
文摘Dear Editor,Emergence of bacteria with multiple drug resistance is a major problem in global public health.Polymyxin comprising polymyxin E（colistin）and polymyxin B is generally recognized as the last-resort antibiotics with broad-spectrum
基金supported by National Key R&D Program of China (2017YFD0500202,YF)National Key Basic Research Program of China (2016YFC1200100,YF)National Natural Science Foundation of China (31570027 & 81772142,YF)
文摘An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome sequencing revealed 5 unique plasmids, namely pHXH-1, pHXH-2, pHXH-3, pHXH-4 and pHXH- 5）. Among them, pHXHI and pHXH4 encode ESBL, and pHXH-5 mediates MCR-1 colistin resistance. The results indicate that the potentially-national dissemination of MCR-l-positive pathogens with pan-drug resistance proceeds via food chains.
文摘Dear Editor,Since 2016, a growing number of mobile colistin resistance(mcr) genes have been identified and characterized (Liu et al., 2016). In addition to mcr-1 and its variants, mcr-2 to mcr-8 have now been reported, which reflects a significant threat to public health and agricultural production (Sun et al.,2018).
文摘The Escherichia coil fadR protein product, a paradigm/ prototypical FadR regulator, positively regulates fabA and fabB, the two critical genes for unsaturated fatty acid （UFA） biosynthesis. However the scenario in the other γ- proteobacteria, such as Shewanella with the marine ori- gin, is unusual in that Rodionov and coworkers predicted that only fabA （not fabB） has a binding site for FadR pro- tein. It raised the possibility of fad regulon contraction. Here we report that this is the case. Sequence alignment of the FadR homologs revealed that the N-terminal DNA- binding domain exhibited remarkable similarity, whereas the ligand-accepting motif at C-terminus is relatively-less conserved. The FadR homologue of S. oneidensis （re- ferred to FadR_she） was over-expressed and purified to homogeneity. Integrative evidence obtained by FPLC （fast protein liquid chromatography） and chemical cross. linking analyses elucidated that FadR_she protein can dimerize in solution, whose identity was determined by MALDI-TOF-MS. In vitro data from electrophoretic mobil. ity shift assays suggested that FadR_she is almost functionally-exchangeable/equivalent to E. coil FadR （FadR_ec） in the ability of binding the E. coil fabA （and fabB） promoters. In an agreement with that of E. coil fabA, S. oneidensis fabA promoter bound both FadR_she andFadR_ec, and was disassociated specifically with the FadR regulatory protein upon the addition of long-chain acyI-CoA thioesters. To monitor in vivo effect exerted by FadR on Shewanella fabA expression, the native pro- moter of S. oneidensis fabA was fused to a LacZ reporter gene to engineer a chromosome fabA-lacZtranscriptional fusion in E. coil. As anticipated, the removal of fadR gene gave about 2-fold decrement of Shewanella fabA expression by β-gal activity, which is almost identical to the inhibitory level by the addition of oleate. Therefore, we concluded that fabA is contracted to be the only one member of fad regulon in the context of fatty acid syn- thesis in the marine bacteria Shewanella genus.
文摘Zika virus （ZIKV） is a previously-neglected, but newly-emerging zoonotic pathogen that has swept most of the western hemisphere. The unexpected attention aroused worldwide lies in the explosive spread of ZIKV to Brazil and USA in 2015 and its rare correlation to micro- cephaly in newborns, raising a serious challenge to public health. We show the origin and fast dissemination of these epidemic ZIKA isolates. Phylogenetic analyses revealed that all the newly-emerging ZIKV isolates belong to the Asian-American Lineage. Structural analyses of the ZIKV E surface protein suggested that it might adopt a similar entry mechanism to that of other Flavi-viruses like Dengue Virus and West Nile Virus.
基金supported by the National Key Research&Development Program of China(2022YFC2303900 and 2022YFC3704700)the National Natural Science Foundation of China(32141001 and 31830001)+1 种基金the National Science Fund for Distinguished Young Scholar(32125003)China Postdoctoral Science Foundation(2022M712797).
文摘Fatty acids (FAs) are building blocks required for the threedomains of life. The machinery of type II fatty acid synthesis is longrecognized as a druggable pathway against deadly infections withdrug-resistant bacterial pathogens [1]. However, an everincreasing body of exogenous FAs (eFA) utilization routes posesthe possibility of replacing bacterial de novo FA synthesis, whichmight compromise the FAS II-directed antimicrobials, like cerulenin[2–4]. As for Gram-negative species, the paradigm executorof an eFA recycling denotes an acyl-ACP synthetase (AasS) of thezoonotic pathogen Vibrio harveyi [5]. In contrast, a unique twocomponent system of fatty acid kinase called FakA/B [6], is exclusively present in Staphylococcus and Enterococcus/Streptococcus,two important lineages of Gram-positive bacterium (Fig. S1a, bonline) [6,7].
基金This work was supported by the National Natural Science Foundation of China(32141001 and 31830001 to Y.F.)the National Science Fund for Distinguished Young Scholar(32125003 to Y.F.)the National Key Basic Research Program of China(2023YFC2307100 and 2023YFC2300021 to Y.F.).
文摘Antimicrobial resistance(AMR)is one of the top global challenges of public health concern.In 2019,it was estimated that AMR claimed around 5 million deaths worldwide[1].Pseudomonas aeruginosa,which originated in soil and water,is recognized as an opportunistic pathogen causing recalcitrant infections.Carbapenem-resistant P.aeruginosa(CRPA)is listed by the World Health Organization(WHO)as an important member of top priority“ESKAPE”pathogens.This is largely supported by the fact that in 2020,CRPA had caused28,8000 nosocomial infections with about 2500 deaths.Apart from porin mutations,the acquisition of Klebsiella pneumoniae carbapenemase(termed as KPC-2)constitutes an alternative mechanism for carbapenem resistance in P.aeruginosa,which compromises the clinical efficacy of the carbapenem as a“last resort”option.Notably,the transferability of blaKPC-2 determinants facilitates global dissemination of CRPA in the context of“one health”consisting of humans,animals,plants/crops,and environmental settings.In addition to antimicrobial stewardship,coordinated global action is necessary to mitigate AMR progression.
文摘Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase （Ga5DH） in cell division of the zoonotic pathogen Strepto- coccus suis. GaSDH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the conse- quence of Ga5DH deprivation in S. suis causing FtsZ delo- calization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that GaSDH may function to prevent the formation of ectopic Z rings during S. suis cell division.
