肺炎克雷伯菌对临床常见抗生素耐药机制研究进展
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摘要
肺炎克雷伯菌广泛分布于自然界,近年来已成为仅次于大肠埃希菌的条件致病菌。由于全世界范围内抗生素的不合理使用,肺炎克雷伯菌对抗生素的耐药性逐年提升,甚至出现了对几乎所有已知抗生素耐药的"超级细菌",给临床抗感染治疗带来了极大的威胁。本文就近年来国内外对肺炎克雷伯菌耐药机制研究的最新进展作一综述。
Klebsiella pneumoniae is widely distributed in the natural world. In recent years, it has become the second opportunistic pathogen only after E. coli. Due to the unreasonable use of the antibiotics worldwide, the drug resistance of Klebsiella pneumoniae is increasing year by year. There have even been "superbugs" resistant to almost all known antibiotics, which pose a great threat to clinical anti-infection treatment. This paper summarizes the recent advances in the study of resistance mechanism of Klebsiella pneumoniae.
Klebsiella pneumoniae is widely distributed in the natural world. In recent years, it has become the second opportunistic pathogen only after E. coli. Due to the unreasonable use of the antibiotics worldwide, the drug resistance of Klebsiella pneumoniae is increasing year by year. There have even been "superbugs" resistant to almost all known antibiotics, which pose a great threat to clinical anti-infection treatment. This paper summarizes the recent advances in the study of resistance mechanism of Klebsiella pneumoniae.
引文
1胡付品,郭燕,朱德妹,等.2017年CHINET中国细菌耐药性监测[J].中国感染与化疗杂志,2018,18(3):241-251.
2 Chong Y,Ito Y,Kamimura T.Genetic evolution and clinical impact in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae[J].Infect Genet Evol,2011,11(7):1499-1504.
3 Calbo E,Garau J.The changing epidemiology of hospital outbreaks due to ESBL-producing Klebsiella pneumoniae:the CTX-M-15 type consolidation[J].Future Microbiol,2015,10(6):1063-1075.
4 Philippon A,Slama P,Deny P,et al.A Structure-Based Classification of Class A beta-Lactamases,a Broadly Diverse Family of Enzymes[J].Clin Microbiol Rev,2016,29(1):29-57.
5 Cuzon G,Naas T,Nordmann P.Functional characterization of Tn4401,a Tn3-based transposon involved in blaKPC gene mobilization[J].Antimicrob Agents Chemother,2011,55(11):5370-5373.
6 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 pneumoniae sequence type 14 from India[J].Antimicrob Agents Chemother,2009,53(12):5046-5054.
7 Bonnin RA,Poirel L,Carattoli A,et al.Characterization of an IncFIIplasmid encoding NDM-1 from Escherichia coli ST131[J].PLoSOne,2012,7(4):e34752.
8 Khan S,Ali A,Khan AU.Structural and functional insight of New Delhi Metallo beta-lactamase-1 variants[J].Future Med Chem,2018,10(2):221-229.
9 Dortet L,Poirel L,Nordmann P.Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria[J/OL].https://www.hindawi.com/journals/bmri/2014/249856.
10 Zamorano L,Miro E,Juan C,et al.Mobile genetic elements related to the diffusion of plasmid-mediated AmpC beta-lactamases or carbapenemases from Enterobacteriaceae:findings from a multicenter study in Spain[J].Antimicrob Agents Chemother,2015,59(9):5260-5266.
11 Poirel L,Bonnin RA,Nordmann P.Genetic features of the widespread plasmid coding for the carbapenemase OXA-48[J].Antimicrob Agents Chemother,2012,56(1):559-562.
12 Padilla E,Llobet E,Domenech-Sanchez A,et al.Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence[J].Antimicrob Agents Chemother,2010,54(1):177-183.
13 Wong MH,Chan EW,Chen S.Evolution and dissemination of OqxAB-like efflux pumps,an emerging quinolone resistance determinant among members of Enterobacteriaceae[J].Antimicrob Agents Chemother,2015,59(6):3290-3297.
14 Doi Y,Wachino JI,Arakawa Y.Aminoglycoside Resistance:The Emergence of Acquired 16S Ribosomal RNA Methyltransferases[J].Infect Dis Clin North Am,2016,30(2):523-537.
15 Poulikakos P,Falagas ME.Aminoglycoside therapy in infectious diseases[J].Expert Opin Pharmacother,2013,14(12):1585-1597.
16 Yu F,Wang L,Pan J,et al.Prevalence of 16S rRNA methylase genes in Klebsiella pneumoniae isolates from a Chinese teaching hospital:coexistence of rmtB and armA genes in the same isolate[J].Diagn Microbiol Infect Dis,2009,64(1):57-63.
17 Krause KM,Serio AW,Kane TR,et al.Aminoglycosides:An Overview[J].Cold Spring Harb Perspect Med,2016,6(6):a027029.
18 De Majumdar S,Yu J,Fookes M,et al.Elucidation of the RamAregulon in Klebsiella pneumoniae reveals a role in LPS regulation[J].PLoS Pathog,2015,11(1):e1004627.
19 Llobet E,Campos MA,Gimenez P,et al.Analysis of the networks controlling the antimicrobial-peptide-dependent induction of Klebsiella pneumoniae virulence factors[J].Infect Immun,2011,79(9):3718-3732.
20 Jayol A,Poirel L,Brink A,et al.Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin[J].Antimicrob Agents Chemother,2014,58(8):4762-4766.
21 Wright MS,Suzuki Y,Jones MB,et al.Genomic and transcriptomic analyses of colistin-resistant clinical isolates of Klebsiella pneumoniae reveal multiple pathways of resistance[J].Antimicrob Agents Chemother,2015,59(1):536-543.
22 Cannatelli A,D'Andrea MM,Giani T,et al.In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator[J].Antimicrob Agents Chemother,2013,57(11):5521-5526.
23 Liu YY,Wang Y,Walsh TR,et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China:a microbiological and molecular biological study[J].Lancet Infect Dis,2016,16(2):161-168.
24 Schwarz S,Johnson AP.Transferable resistance to colistin:a new but old threat[J].J Antimicrob Chemother,2016,71(8):2066-2070.
25 Di Pilato V,Arena F,Tascini C,et al.mcr-1.2,a New mcr Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPCCarbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512[J].Antimicrob Agents Chemother,2016,60(9):5612-5615.
26 Kidd TJ,Mills G,Sa-Pessoa J,et al.A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence[J].EMBO Mol Med,2017,9(4):430-447.
27 Wang X,Wang Y,Zhou Y,et al.Emergence of a novel mobile colistin resistance gene,mcr-8,in NDM-producing Klebsiella pneumoniae[J].Emerg Microbes Infect,2018,7(1):122.
28 Osei Sekyere J,Govinden U,Bester LA,et al.Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria:emerging resistance mechanisms and detection methods[J].J Appl Microbiol,2016,121(3):601-617.
29 Kallman O,Motakefi A,Wretlind B,et al.Cefuroxime nonsusceptibility in multidrug-resistant Klebsiella pneumoniae overexpressing ramA and acrA and expressing ompK35 at reduced levels[J].J Antimicrob Chemother,2008,62(5):986-990.
30 Villa L,Feudi C,Fortini D,et al.Genomics of KPC-producing Klebsiella pneumoniae sequence type 512 clone highlights the role of RamR and ribosomal S10 protein mutations in conferring tigecycline resistance[J].Antimicrob Agents Chemother,2014,58(3):1707-1712.
31 Ahn C,Yoon SS,Yong TS,et al.The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella pneumoniae Isolates in Korea[J].Yonsei Med J,2016,57(3):641-646.
32 Zhong X,Xu H,Chen D,et al.First emergence of acrAB and oqxABmediated tigecycline resistance in clinical isolates of Klebsiella pneumoniae pre-dating the use of tigecycline in a Chinese hospital[J].PLoS One,2014,9(12):e115185.
33 Ye M,Ding B,Qian H,et al.In vivo development of tigecycline resistance in Klebsiella pneumoniae owing to deletion of the ramRribosomal binding site[J].Int J Antimicrob Agents,2017,50(4):523-528.
2 Chong Y,Ito Y,Kamimura T.Genetic evolution and clinical impact in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae[J].Infect Genet Evol,2011,11(7):1499-1504.
3 Calbo E,Garau J.The changing epidemiology of hospital outbreaks due to ESBL-producing Klebsiella pneumoniae:the CTX-M-15 type consolidation[J].Future Microbiol,2015,10(6):1063-1075.
4 Philippon A,Slama P,Deny P,et al.A Structure-Based Classification of Class A beta-Lactamases,a Broadly Diverse Family of Enzymes[J].Clin Microbiol Rev,2016,29(1):29-57.
5 Cuzon G,Naas T,Nordmann P.Functional characterization of Tn4401,a Tn3-based transposon involved in blaKPC gene mobilization[J].Antimicrob Agents Chemother,2011,55(11):5370-5373.
6 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 pneumoniae sequence type 14 from India[J].Antimicrob Agents Chemother,2009,53(12):5046-5054.
7 Bonnin RA,Poirel L,Carattoli A,et al.Characterization of an IncFIIplasmid encoding NDM-1 from Escherichia coli ST131[J].PLoSOne,2012,7(4):e34752.
8 Khan S,Ali A,Khan AU.Structural and functional insight of New Delhi Metallo beta-lactamase-1 variants[J].Future Med Chem,2018,10(2):221-229.
9 Dortet L,Poirel L,Nordmann P.Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria[J/OL].https://www.hindawi.com/journals/bmri/2014/249856.
10 Zamorano L,Miro E,Juan C,et al.Mobile genetic elements related to the diffusion of plasmid-mediated AmpC beta-lactamases or carbapenemases from Enterobacteriaceae:findings from a multicenter study in Spain[J].Antimicrob Agents Chemother,2015,59(9):5260-5266.
11 Poirel L,Bonnin RA,Nordmann P.Genetic features of the widespread plasmid coding for the carbapenemase OXA-48[J].Antimicrob Agents Chemother,2012,56(1):559-562.
12 Padilla E,Llobet E,Domenech-Sanchez A,et al.Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence[J].Antimicrob Agents Chemother,2010,54(1):177-183.
13 Wong MH,Chan EW,Chen S.Evolution and dissemination of OqxAB-like efflux pumps,an emerging quinolone resistance determinant among members of Enterobacteriaceae[J].Antimicrob Agents Chemother,2015,59(6):3290-3297.
14 Doi Y,Wachino JI,Arakawa Y.Aminoglycoside Resistance:The Emergence of Acquired 16S Ribosomal RNA Methyltransferases[J].Infect Dis Clin North Am,2016,30(2):523-537.
15 Poulikakos P,Falagas ME.Aminoglycoside therapy in infectious diseases[J].Expert Opin Pharmacother,2013,14(12):1585-1597.
16 Yu F,Wang L,Pan J,et al.Prevalence of 16S rRNA methylase genes in Klebsiella pneumoniae isolates from a Chinese teaching hospital:coexistence of rmtB and armA genes in the same isolate[J].Diagn Microbiol Infect Dis,2009,64(1):57-63.
17 Krause KM,Serio AW,Kane TR,et al.Aminoglycosides:An Overview[J].Cold Spring Harb Perspect Med,2016,6(6):a027029.
18 De Majumdar S,Yu J,Fookes M,et al.Elucidation of the RamAregulon in Klebsiella pneumoniae reveals a role in LPS regulation[J].PLoS Pathog,2015,11(1):e1004627.
19 Llobet E,Campos MA,Gimenez P,et al.Analysis of the networks controlling the antimicrobial-peptide-dependent induction of Klebsiella pneumoniae virulence factors[J].Infect Immun,2011,79(9):3718-3732.
20 Jayol A,Poirel L,Brink A,et al.Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin[J].Antimicrob Agents Chemother,2014,58(8):4762-4766.
21 Wright MS,Suzuki Y,Jones MB,et al.Genomic and transcriptomic analyses of colistin-resistant clinical isolates of Klebsiella pneumoniae reveal multiple pathways of resistance[J].Antimicrob Agents Chemother,2015,59(1):536-543.
22 Cannatelli A,D'Andrea MM,Giani T,et al.In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator[J].Antimicrob Agents Chemother,2013,57(11):5521-5526.
23 Liu YY,Wang Y,Walsh TR,et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China:a microbiological and molecular biological study[J].Lancet Infect Dis,2016,16(2):161-168.
24 Schwarz S,Johnson AP.Transferable resistance to colistin:a new but old threat[J].J Antimicrob Chemother,2016,71(8):2066-2070.
25 Di Pilato V,Arena F,Tascini C,et al.mcr-1.2,a New mcr Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPCCarbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512[J].Antimicrob Agents Chemother,2016,60(9):5612-5615.
26 Kidd TJ,Mills G,Sa-Pessoa J,et al.A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence[J].EMBO Mol Med,2017,9(4):430-447.
27 Wang X,Wang Y,Zhou Y,et al.Emergence of a novel mobile colistin resistance gene,mcr-8,in NDM-producing Klebsiella pneumoniae[J].Emerg Microbes Infect,2018,7(1):122.
28 Osei Sekyere J,Govinden U,Bester LA,et al.Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria:emerging resistance mechanisms and detection methods[J].J Appl Microbiol,2016,121(3):601-617.
29 Kallman O,Motakefi A,Wretlind B,et al.Cefuroxime nonsusceptibility in multidrug-resistant Klebsiella pneumoniae overexpressing ramA and acrA and expressing ompK35 at reduced levels[J].J Antimicrob Chemother,2008,62(5):986-990.
30 Villa L,Feudi C,Fortini D,et al.Genomics of KPC-producing Klebsiella pneumoniae sequence type 512 clone highlights the role of RamR and ribosomal S10 protein mutations in conferring tigecycline resistance[J].Antimicrob Agents Chemother,2014,58(3):1707-1712.
31 Ahn C,Yoon SS,Yong TS,et al.The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella pneumoniae Isolates in Korea[J].Yonsei Med J,2016,57(3):641-646.
32 Zhong X,Xu H,Chen D,et al.First emergence of acrAB and oqxABmediated tigecycline resistance in clinical isolates of Klebsiella pneumoniae pre-dating the use of tigecycline in a Chinese hospital[J].PLoS One,2014,9(12):e115185.
33 Ye M,Ding B,Qian H,et al.In vivo development of tigecycline resistance in Klebsiella pneumoniae owing to deletion of the ramRribosomal binding site[J].Int J Antimicrob Agents,2017,50(4):523-528.