碳青霉烯类抗生素超级耐药细菌检测及抗菌策略研究进展
|
摘要
抗生素的滥用导致越来越多"超级细菌"的出现,对几乎所有已知抗生素耐药,严重危害人类健康。碳青霉烯类抗生素是治疗革兰阴性杆菌感染的最强效β-内酰胺类药物,但近年来出现的耐碳青霉烯类肠杆菌可将其水解,对抗感染治疗构成极大威胁。由于传统抗生素类治疗发展缓慢且疗效有限,新型抗菌药物和疗法的研究开发成为对抗超级耐药菌感染的重要发展方向。本文总结了超级细菌的新型快速检测技术和抗菌策略等方面的研究进展,为实验室研究和临床治疗提供参考。
The overuse of antibiotics has led to the emergence of more and more superbugs that are resistant to almost all known types of antibiotics and that pose a serious threat to public health.The emergence of carbapenem-resistant Enterobacteriaceae in recent years has greatly hampered the treatment of infections since the strains can hydrolyze carbapenems,which have been the most useful beta-lactam antibiotics against Gram-negative bacilli.Due to the slow development and limited effectiveness of traditional antibiotics,development of novel antimicrobial agents and therapeutics against infections caused by superbugs is crucial.This review summarizes advances in the study of new methods to screen for superbugs and new antimicrobial strategies to guide basic research and clinical treatment.
The overuse of antibiotics has led to the emergence of more and more superbugs that are resistant to almost all known types of antibiotics and that pose a serious threat to public health.The emergence of carbapenem-resistant Enterobacteriaceae in recent years has greatly hampered the treatment of infections since the strains can hydrolyze carbapenems,which have been the most useful beta-lactam antibiotics against Gram-negative bacilli.Due to the slow development and limited effectiveness of traditional antibiotics,development of novel antimicrobial agents and therapeutics against infections caused by superbugs is crucial.This review summarizes advances in the study of new methods to screen for superbugs and new antimicrobial strategies to guide basic research and clinical treatment.
引文
[1]Magiorakos AP,Srinivasan A,Carey RB,et al.Multidrug-resistant,extensively drug-resistant and pandrug-resistant bacteria:an international expert proposal for interim standard definitions for acquired resistance[J].Clin Microbiol Infect,2012,18(3):268-81.
[2]邹全明,石云.超级细菌疫苗研究进展[J].第三军医大学学报,2016,38(7):663-8.
[3]Yong D,Toleman MA,Giske CG,et al.Characterization of a new metallo-beta-lactamase gene,bla(NDM-1),and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumonia sequence type 14from India[J].Antimicrob Agents Ch,2009,53(12):5046-54.
[4]Sun J,Yang RS,Zhang QJ,et al.Co-transfer of blaNDM-5and mcr-1by an IncX3-X4hybrid plasmid in Escherichia coli[J].Nat Microbiol,2016(1):16176.
[5]Nikaido H,Pages JM.Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria[J].FEMS Microbiol Rev,2012,36(2):340-63.
[6]陈惠玲,邓家德,叶惠芬,等.低产碳青霉烯酶肠杆菌科细菌的筛选及耐药基因检测[J].实用医学杂志,2012,28(2):310-2.
[7]Queenan AM,Bush K.Carbapenemases:the versatile beta-lactamases[J].Clin Microbiol Rev,2007,20(3):440-58.
[8]Walsh TR,Toleman MA,Poirel L,et al.Metallo-beta-lactamases:the quiet before the storm?[J].Clin Microbiol Rev,2005,18(2):306-25.
[9]Potron A,Poirel L,Nordmann P.Plasmid-mediated transfer of the bla(NDM-1)gene in Gram-negative rods[J].FEMS Microbiol Lett,2011,324(2):111-6.
[10]Nordmann P,Poirel L,Carrer A,et al.How to detect NDM-1producers[J].J Clin Microbiol,2011,49(2):718-21.
[11]Cuzon G,Naas T,Bogaerts P,et al.Evaluation of a DNA microarray for the rapid detection of extended-spectrum beta-lactamases(TEM,SHV and CTX-M),plasmid-mediated cephalosporinases(CMY-2-like,DHA,FOX,ACC-1,ACT/MIR and CMY-1-like/MOX)and carbapenemases(KPC,OXA-48,VIM,IMP and NDM)[J].J Antimicrob Chemother,2012,67(8):1865-9.
[12]Solanki R,Vanjari L,Ede N,et al.Evaluation of LAMP assay using phenotypic tests and conventional PCR for detection of blaNDM-1and blaKPC genes among carbapenem-resistant clinical Gram-negative isolates[J].J Med Microbiol,2013,62(10):1540-4.
[13]施开创,李凤梅,张步娴,等.超级细菌blaNDM-1基因TaqMan-MGB荧光定量PCR检测[J].中国预防兽医学报,2015,37(12):952-6.
[14]朱水荣,王志刚,潘军航,等.PCR/LAMP快速筛检NDM-1超级耐药菌的方法建立[J].中国卫生检验杂志,2011,21(4):790-3.
[15]Zhai Q,Pang J,Li G,et al.Validated LC--MS/MS method for determination of YH-8,a novel PKnB inhibitor,in rat plasma and its application to pharmacokinetic study[J].Acta Pharm Sin B,2015,5(5):467-72.
[16]Huang L,Hu X,Zhou M,et al.Rapid detection of New Delhi metallo-beta-lactamase gene and variants coding for carbapenemases with different activities by use of a PCR-based in vitro protein expression method[J].J Clin Microbiol,2014,52(6):1947-53.
[17]王志明.抗生素研发新方向:抗菌抗体药物[J].中国新药杂志,2016,25(19):2199-203.
[18]Schieber AM,Lee YM,Chang MW,et al.Disease tolerance mediated by microbiome E.coli involves inflammasome and IGF-1signaling[J].Science,2015,350(6260):558-63.
[19]Rebuffat S.Microcins in action:amazing defence strategies of Enterobacteria[J].Biochem Soc Trans,2012,40(6):1456-62.
[20]Sassone-Corsi M,Nuccio SP,Liu H,et al.Microcins mediate competition among Enterobacteriaceae in the inflamed gut[J].Nature,2016,540(7632):280-3.
[21]李兴华,肖春玲.NDM-1酶及其抑制剂研究进展.中国新药杂志,2016,25(3):270-6.
[22]Fowler VG,Allen KB,Moreira ED,et al.Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery:a randomized trial[J].JAMA,2013,309(13):1368-78.
[23]Doring G,Meisner C,Stern M,et al.A double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients[J].Proc Natl Acad Sci U S A,2007,104(26):11020-5.
[24]Pachon J,McConnell MJ.Considerations for the development of aprophylactic vaccine for Acinetobacter baumannii[J].Vaccine,2014,32(22):2534-6.
[25]郭婷婷,李玲,孙元章,等.细菌性疾病的新疗法--噬菌体疗法[J].生命科学,2016,28(7):817-3.
[26]Pincus NB,Reckhow JD,Saleem D,et al.Strain specific phage treatment for Staphylococcus aureus infection is influenced by host immunity and site of infection[J].PLoS One,2015,10(4):e0124280.
[27]Harper DR,Morales S.Bacteriophage therapy:Practicability and clinical need meet in the multidrug-resistance era[J].Future Microbiol,2012,7(7):797-9.
[28]Makarova KS,Haft DH,Barrangou R,et al.Evolution and classification of the CRISPR-Cas systems[J].Nat Rev Microbiol,2011,9(6):467-77.
[29]Hsu PD,Lander ES,Zhang F.Development and applications of CRISPR-Cas9for genome engineering[J].Cell,2014,157(6):1262-78.
[30]Cong L,Ran FA,Cox D,et al.Multiplex genome engineering using CRISPR/Cas systems[J].Science,2013,339(6121):819-23.
[31]Lin TL,Pan YJ,Hsieh PF,et al.Imipenem represses CRISPRCas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae[J].Sci Rep,2016(6):31644-53.
[32]Choi KR,Lee SY.CRISPR technologies for bacterial systems:Current achievements and future directions[J].Biotechnol Adv,2016,34(7):1180-209.
[33]Gomaa AA,Klumpe HE,Luo ML,et al.Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems[J].MBio,2014,5(1):e00928-13.
[34]Bikard D,Euler CW,Jiang W,et al.Development of sequencespecific antimicrobials based on programmable CRISPR-Cas nucleases[J].Nat Biotechnol,2014,32(11):1146-50.
[35]Citorik RJ,Mimee M,Lu TK.Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases[J].Nat Biotechnol,2014,32(11):1141-5.
[36]高杰,李英,王文英.儿科患者感染大肠埃希菌耐药性及其对碳青霉烯类和氨基糖苷类药物耐药机制研究[J].中国病原生物学杂志,2016,11(2):164-8.
[37]Schaefer KA,Wu W,Colgan DF,et al.Unexpected mutations after CRISPR-Cas9editing in vivo[J].Nat Methods 2017,14(6):547-8.
[2]邹全明,石云.超级细菌疫苗研究进展[J].第三军医大学学报,2016,38(7):663-8.
[3]Yong D,Toleman MA,Giske CG,et al.Characterization of a new metallo-beta-lactamase gene,bla(NDM-1),and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumonia sequence type 14from India[J].Antimicrob Agents Ch,2009,53(12):5046-54.
[4]Sun J,Yang RS,Zhang QJ,et al.Co-transfer of blaNDM-5and mcr-1by an IncX3-X4hybrid plasmid in Escherichia coli[J].Nat Microbiol,2016(1):16176.
[5]Nikaido H,Pages JM.Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria[J].FEMS Microbiol Rev,2012,36(2):340-63.
[6]陈惠玲,邓家德,叶惠芬,等.低产碳青霉烯酶肠杆菌科细菌的筛选及耐药基因检测[J].实用医学杂志,2012,28(2):310-2.
[7]Queenan AM,Bush K.Carbapenemases:the versatile beta-lactamases[J].Clin Microbiol Rev,2007,20(3):440-58.
[8]Walsh TR,Toleman MA,Poirel L,et al.Metallo-beta-lactamases:the quiet before the storm?[J].Clin Microbiol Rev,2005,18(2):306-25.
[9]Potron A,Poirel L,Nordmann P.Plasmid-mediated transfer of the bla(NDM-1)gene in Gram-negative rods[J].FEMS Microbiol Lett,2011,324(2):111-6.
[10]Nordmann P,Poirel L,Carrer A,et al.How to detect NDM-1producers[J].J Clin Microbiol,2011,49(2):718-21.
[11]Cuzon G,Naas T,Bogaerts P,et al.Evaluation of a DNA microarray for the rapid detection of extended-spectrum beta-lactamases(TEM,SHV and CTX-M),plasmid-mediated cephalosporinases(CMY-2-like,DHA,FOX,ACC-1,ACT/MIR and CMY-1-like/MOX)and carbapenemases(KPC,OXA-48,VIM,IMP and NDM)[J].J Antimicrob Chemother,2012,67(8):1865-9.
[12]Solanki R,Vanjari L,Ede N,et al.Evaluation of LAMP assay using phenotypic tests and conventional PCR for detection of blaNDM-1and blaKPC genes among carbapenem-resistant clinical Gram-negative isolates[J].J Med Microbiol,2013,62(10):1540-4.
[13]施开创,李凤梅,张步娴,等.超级细菌blaNDM-1基因TaqMan-MGB荧光定量PCR检测[J].中国预防兽医学报,2015,37(12):952-6.
[14]朱水荣,王志刚,潘军航,等.PCR/LAMP快速筛检NDM-1超级耐药菌的方法建立[J].中国卫生检验杂志,2011,21(4):790-3.
[15]Zhai Q,Pang J,Li G,et al.Validated LC--MS/MS method for determination of YH-8,a novel PKnB inhibitor,in rat plasma and its application to pharmacokinetic study[J].Acta Pharm Sin B,2015,5(5):467-72.
[16]Huang L,Hu X,Zhou M,et al.Rapid detection of New Delhi metallo-beta-lactamase gene and variants coding for carbapenemases with different activities by use of a PCR-based in vitro protein expression method[J].J Clin Microbiol,2014,52(6):1947-53.
[17]王志明.抗生素研发新方向:抗菌抗体药物[J].中国新药杂志,2016,25(19):2199-203.
[18]Schieber AM,Lee YM,Chang MW,et al.Disease tolerance mediated by microbiome E.coli involves inflammasome and IGF-1signaling[J].Science,2015,350(6260):558-63.
[19]Rebuffat S.Microcins in action:amazing defence strategies of Enterobacteria[J].Biochem Soc Trans,2012,40(6):1456-62.
[20]Sassone-Corsi M,Nuccio SP,Liu H,et al.Microcins mediate competition among Enterobacteriaceae in the inflamed gut[J].Nature,2016,540(7632):280-3.
[21]李兴华,肖春玲.NDM-1酶及其抑制剂研究进展.中国新药杂志,2016,25(3):270-6.
[22]Fowler VG,Allen KB,Moreira ED,et al.Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery:a randomized trial[J].JAMA,2013,309(13):1368-78.
[23]Doring G,Meisner C,Stern M,et al.A double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients[J].Proc Natl Acad Sci U S A,2007,104(26):11020-5.
[24]Pachon J,McConnell MJ.Considerations for the development of aprophylactic vaccine for Acinetobacter baumannii[J].Vaccine,2014,32(22):2534-6.
[25]郭婷婷,李玲,孙元章,等.细菌性疾病的新疗法--噬菌体疗法[J].生命科学,2016,28(7):817-3.
[26]Pincus NB,Reckhow JD,Saleem D,et al.Strain specific phage treatment for Staphylococcus aureus infection is influenced by host immunity and site of infection[J].PLoS One,2015,10(4):e0124280.
[27]Harper DR,Morales S.Bacteriophage therapy:Practicability and clinical need meet in the multidrug-resistance era[J].Future Microbiol,2012,7(7):797-9.
[28]Makarova KS,Haft DH,Barrangou R,et al.Evolution and classification of the CRISPR-Cas systems[J].Nat Rev Microbiol,2011,9(6):467-77.
[29]Hsu PD,Lander ES,Zhang F.Development and applications of CRISPR-Cas9for genome engineering[J].Cell,2014,157(6):1262-78.
[30]Cong L,Ran FA,Cox D,et al.Multiplex genome engineering using CRISPR/Cas systems[J].Science,2013,339(6121):819-23.
[31]Lin TL,Pan YJ,Hsieh PF,et al.Imipenem represses CRISPRCas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae[J].Sci Rep,2016(6):31644-53.
[32]Choi KR,Lee SY.CRISPR technologies for bacterial systems:Current achievements and future directions[J].Biotechnol Adv,2016,34(7):1180-209.
[33]Gomaa AA,Klumpe HE,Luo ML,et al.Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems[J].MBio,2014,5(1):e00928-13.
[34]Bikard D,Euler CW,Jiang W,et al.Development of sequencespecific antimicrobials based on programmable CRISPR-Cas nucleases[J].Nat Biotechnol,2014,32(11):1146-50.
[35]Citorik RJ,Mimee M,Lu TK.Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases[J].Nat Biotechnol,2014,32(11):1141-5.
[36]高杰,李英,王文英.儿科患者感染大肠埃希菌耐药性及其对碳青霉烯类和氨基糖苷类药物耐药机制研究[J].中国病原生物学杂志,2016,11(2):164-8.
[37]Schaefer KA,Wu W,Colgan DF,et al.Unexpected mutations after CRISPR-Cas9editing in vivo[J].Nat Methods 2017,14(6):547-8.