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European Journal of Clinical Microbiology & Infectious Diseases

Erschienen in:

17.04.2018 | Review

Plasmids carrying DHA-1 β-lactamases

verfasst von: Claire Hennequin, Viviane Ravet, Frédéric Robin

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 7/2018

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Abstract

The aim of this review is to provide an update on the plasmids mediating DHA-1 cephalosporinase in Klebsiella pneumoniae. These plasmids have been mainly found in this bacterium but not only. The first was isolated from Salmonella sp. in France in the early 1990s. They are currently reported worldwide. Bla_DHA-1 beta-lactamase gene is usually co-expressed with many other antibiotic resistance genes such as extended-spectrum β-lactamases (bla_CTX-M-, bla_SHV-types), oxacillinases (bla_OXA-1, bla_OXA-30), penicillinases (bla_TEM-type), carbapenemases (bla_OXA48, bla_KPC-2), aminoglycosides (aacA, aadA, armA), fluoroquinolones (qnrB4, aac6′-1b-cr), and sulfonamide (sul1) resistance genes. Plasmids carrying DHA-1 cephalosporinase have different sizes (22 to 313 kb), belong to diverse groups of incompatibility (R, L/M, FII(k), FIB, A/C2, HI2, HIB), and are self-transferable or not. The multidrug resistance region consists of a mosaic structure composed of resistance genes, insertion sequences, composite transposon, and integrons.

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Jacoby GA (2009) AmpC beta-lactamases. Clin Microbiol Rev 22:161–182, Table of Contents. https://doi.org/10.1128/CMR.00036-08 CrossRefPubMedPubMedCentral

Papanicolaou GA, Medeiros AA, Jacoby GA (1990) Novel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 34:2200–2209CrossRefPubMedPubMedCentral

Philippon A, Arlet G, Jacoby GA (2002) Plasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother 46:1–11CrossRefPubMedPubMedCentral

Gaillot O, Clément C, Simonet M, Philippon A (1997) Novel transferable beta-lactam resistance with cephalosporinase characteristics in Salmonella enteritidis. J Antimicrob Chemother 39:85–87CrossRefPubMed

Ambler RP (1980) The structure of beta-lactamases. Philos Trans R Soc Lond Ser B Biol Sci 289:321–331CrossRef

Bush K, Jacoby GA, Medeiros AA (1995) A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 39:1211–1233CrossRefPubMedPubMedCentral

Nourrisson C, Tan RN, Hennequin C, Gibold L, Bonnet R, Robin F (2015) The MAST® D68C test: an interesting tool for detecting extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 34:975–983. https://doi.org/10.1007/s10096-014-2305-6 CrossRef

Maraskolhe DL, Deotale VS, Mendiratta DK, Narang P (2014) Comparision of three laboratory tests for detection of AmpC β lactamases in Klebsiella species and E. coli. J Clin Diagn Res JCDR 8:DC05–DC08. https://doi.org/10.7860/JCDR/2014/8256.4432 PubMedCrossRef

Reuland EA, Hays JP, de Jongh DMC, Abdelrehim E, Willemsen I, Kluytmans JAJW et al (2014) Detection and occurrence of plasmid-mediated AmpC in highly resistant gram-negative rods. PLoS One 9:e91396. https://doi.org/10.1371/journal.pone.0091396 CrossRefPubMedPubMedCentral

10.

Edquist P, Ringman M, Liljequist BO, Wisell KT, Giske CG (2013) Phenotypic detection of plasmid-acquired AmpC in Escherichia coli—evaluation of screening criteria and performance of two commercial methods for the phenotypic confirmation of AmpC production. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 32:1205–1210. https://doi.org/10.1007/s10096-013-1869-x CrossRef

11.

Pérez-Pérez FJ, Hanson ND (2002) Detection of plasmid-mediated AmpC beta-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol 40:2153–2162CrossRefPubMedPubMedCentral

12.

Alvarez M, Tran JH, Chow N, Jacoby GA (2004) Epidemiology of conjugative plasmid-mediated AmpC beta-lactamases in the United States. Antimicrob Agents Chemother 48:533–537CrossRefPubMedPubMedCentral

13.

Moland ES, Black JA, Ourada J, Reisbig MD, Hanson ND, Thomson KS (2002) Occurrence of newer beta-lactamases in Klebsiella pneumoniae isolates from 24 U.S. hospitals. Antimicrob Agents Chemother 46:3837–3842CrossRefPubMed

14.

Liebana E, Batchelor M, Clifton-Hadley FA, Davies RH, Hopkins KL, Threlfall EJ (2004) First report of Salmonella isolates with the DHA-1 Amp. beta-lactamase in the United Kingdom. Antimicrob Agents Chemother 48:4492. https://doi.org/10.1128/AAC.48.11.4492.2004 CrossRefPubMedPubMedCentral

15.

Verdet C, Benzerara Y, Gautier V, Adam O, Ould-Hocine Z, Arlet G (2006) Emergence of DHA-1-producing Klebsiella spp. in the Parisian region: genetic organization of the ampC and ampR genes originating from Morganella morganii. Antimicrob Agents Chemother 50:607–617. https://doi.org/10.1128/AAC.50.2.607-617.2006 CrossRefPubMedPubMedCentral

16.

Pai H, Kang C-I, Byeon J-H, Lee K-D, Park WB, Kim H-B et al (2004) Epidemiology and clinical features of bloodstream infections caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 48:3720–3728. https://doi.org/10.1128/AAC.48.10.3720-3728.2004 CrossRefPubMedPubMedCentral

17.

Pai H, Seo M-R, Choi TY (2007) Association of QnrB determinants and production of extended-spectrum beta-lactamases or plasmid-mediated AmpC beta-lactamases in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 51:366–368. https://doi.org/10.1128/AAC.00841-06 CrossRefPubMed

18.

Yan J-J, Ko W-C, Jung Y-C, Chuang C-L, Wu J-J (2002) Emergence of Klebsiella pneumoniae isolates producing inducible DHA-1 beta-lactamase in a university hospital in Taiwan. J Clin Microbiol 40:3121–3126CrossRefPubMedPubMedCentral

19.

Kim J-Y, Park Y-J, Lee S-O, Song W, Jeong SH, Yoo YA et al (2004) Case report: bacteremia due to Salmonella enterica serotype Montevideo producing plasmid-mediated AmpC beta-lactamase (DHA-1). Ann Clin Lab Sci 34:214–217PubMed

20.

Yan J-J, Ko W-C, Wu H-M, Tsai S-H, Chuang C-L, Wu J-J (2004) Complexity of Klebsiella pneumoniae isolates resistant to both cephamycins and extended-spectrum cephalosporins at a teaching hospital in Taiwan. J Clin Microbiol 42:5337–5340. https://doi.org/10.1128/JCM.42.11.5337-5340.2004 CrossRefPubMedPubMedCentral

21.

Roh KH, Uh Y, Kim J-S, Kim H-S, Shin DH, Song W (2008) First outbreak of multidrug-resistant Klebsiella pneumoniae producing both SHV-12-type extended-spectrum beta-lactamase and DHA-1-type AmpC beta-lactamase at a Korean hospital. Yonsei Med J 49:53–57. https://doi.org/10.3349/ymj.2008.49.1.53 CrossRefPubMedPubMedCentral

22.

Tamang MD, Seol SY, Oh J-Y, Kang HY, Lee JC, Lee YC et al (2008) Plasmid-mediated quinolone resistance determinants qnrA, qnrB, and qnrS among clinical isolates of Enterobacteriaceae in a Korean hospital. Antimicrob Agents Chemother 52:4159–4162. https://doi.org/10.1128/AAC.01633-07 CrossRefPubMedPubMedCentral

23.

Hu F, Xu X, Zhu D, Wang M (2008) Coexistence of qnrB4 and qnrS1 in a clinical strain of Klebsiella pneumoniae. Acta Pharmacol Sin 29:320–324. https://doi.org/10.1111/j.1745-7254.2008.00757.x CrossRefPubMed

24.

Lee C-H, Liu J-W, Li C-C, Chien C-C, Tang Y-F, Su L-H (2011) Spread of ISCR1 elements containing bla DHA- ₁ and multiple antimicrobial resistance genes leading to increase of flomoxef resistance in extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 55:4058–4063. https://doi.org/10.1128/AAC.00259-11 CrossRefPubMedPubMedCentral

25.

Jiang Y, Yu D, Wei Z, Shen P, Zhou Z, Yu Y (2010) Complete nucleotide sequence of Klebsiella pneumoniae multidrug resistance plasmid pKP048, carrying bla _KPC-2, bla _DHA-1, qnrB4, and armA. Antimicrob Agents Chemother 54:3967–3969. https://doi.org/10.1128/AAC.00137-10 CrossRefPubMedPubMedCentral

26.

Zhang D, Yin Z, Zhao Y, Feng J, Jiang X, Zhan Z et al (2017) p1220-CTXM, a pKP048-related IncFIIK plasmid carrying bla _CTX-M-14 and qnrB4. Future Microbiol 12:1035–1043. https://doi.org/10.2217/fmb-2017-0026 CrossRefPubMed

27.

Vanwynsberghe T, Verhamme K, Raymaekers M, Cartuyvels R, Boel A, De Beenhouwer H (2007) Outbreak of Klebsiella pneumoniae strain harbouring an AmpC (DHA-1) and a bla _SHV-11 in a Belgian hospital, August–December 2006. Eur Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull 12:E070201.3

28.

Mata C, Miró E, Toleman M, Rivera MA, Walsh TR, Navarro F (2011) Association of bla(DHA-1) and qnrB genes carried by broad-host-range plasmids among isolates of Enterobacteriaceae at a Spanish hospital. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 17:1514–1517. https://doi.org/10.1111/j.1469-0691.2011.03539.x CrossRef

29.

Diestra K, Miró E, Martí C, Navarro D, Cuquet J, Coll P et al (2011) Multiclonal epidemic of Klebsiella pneumoniae isolates producing DHA-1 in a Spanish hospital. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 17:1032–1036. https://doi.org/10.1111/j.1469-0691.2010.03319.x CrossRef

30.

Yu F, Chen C, Chen Q, Yu X, Ding B, Yang L et al (2012) Identification of transferable DHA-1 type AmpC β-lactamases and two mutations in quinolone resistance-determining regions of Salmonella enterica serovar Thompson. J Med Microbiol 61:460–462. https://doi.org/10.1099/jmm.0.040691-0 CrossRefPubMed

31.

Yim G, Kwong W, Davies J, Miao V (2013) Complex integrons containing qnrB4-ampC (bla(DHA-1)) in plasmids of multidrug-resistant Citrobacter freundii from wastewater. Can J Microbiol 59:110–116. https://doi.org/10.1139/cjm-2012-0576 CrossRefPubMed

32.

Pérez-Moreno MO, Estepa V, Sáenz Y, Cortell-Ortolá M, Fort-Gallifa I, Ruiz J et al (2012) Intrahospitalary dissemination of Klebsiella pneumoniae carrying bla(DHA-1) and qnrB4 genes within a novel complex class 1 integron. Diagn Microbiol Infect Dis 73:210–211. https://doi.org/10.1016/j.diagmicrobio.2012.02.011 CrossRefPubMed

33.

Guo Q, Wang P, Ma Y, Yang Y, Ye X, Wang M (2012) Co-production of SFO-1 and DHA-1 β-lactamases and 16S rRNA methylase ArmA in clinical isolates of Klebsiella pneumoniae. J Antimicrob Chemother 67:2361–2366. https://doi.org/10.1093/jac/dks244 CrossRefPubMed

34.

Compain F, Frangeul L, Drieux L, Verdet C, Brisse S, Arlet G et al (2014) Complete nucleotide sequence of two multidrug-resistant IncR plasmids from Klebsiella pneumoniae. Antimicrob Agents Chemother 58:4207–4210. https://doi.org/10.1128/AAC.02773-13 CrossRefPubMedPubMedCentral

35.

Tobes R, Codoñer FM, López-Camacho E, Salanueva IJ, Manrique M, Brozynska M et al (2013) Genome sequence of Klebsiella pneumoniae KpQ3, a DHA-1 β-lactamase-producing nosocomial isolate. Genome Announc 1. https://doi.org/10.1128/genomeA.00167-12

36.

Compain F, Decré D, Fulgencio J-P, Berraho S, Arlet G, Verdet C (2014) Molecular characterization of DHA-1-producing Klebsiella pneumoniae isolates collected during a 4-year period in an intensive care unit. Diagn Microbiol Infect Dis 80:159–161. https://doi.org/10.1016/j.diagmicrobio.2014.06.009 CrossRefPubMed

37.

Hidalgo L, Gutierrez B, Ovejero CM, Carrilero L, Matrat S, Saba CKS et al (2013) Klebsiella pneumoniae sequence type 11 from companion animals bearing ArmA methyltransferase, DHA-1 β-lactamase, and QnrB4. Antimicrob Agents Chemother 57:4532–4534. https://doi.org/10.1128/AAC.00491-13 CrossRefPubMedPubMedCentral

38.

Ho PL, Lo WU, Yeung MK, Lin CH, Chow KH, Ang I et al (2011) Complete sequencing of pNDM-HK encoding NDM-1 carbapenemase from a multidrug-resistant Escherichia coli strain isolated in Hong Kong. PLoS One 6:e17989. https://doi.org/10.1371/journal.pone.0017989 CrossRefPubMedPubMedCentral

39.

Voulgari E, Poulou A, Dimitroulia E, Politi L, Ranellou K, Gennimata V et al (2015) Emergence of OXA-162 carbapenemase- and DHA-1 Amp. cephalosporinase-producing sequence type 11 Klebsiella pneumoniae causing community-onset infection in Greece. Antimicrob Agents Chemother 60:1862–1864. https://doi.org/10.1128/AAC.01514-15 CrossRefPubMed

40.

Kuai S, Shao H, Huang L, Pei H, Lu Z, Wang W et al (2014) KPC-2 carbapenemase and DHA-1 Amp. determinants carried on the same plasmid in Enterobacter aerogenes. J Med Microbiol 63:367–370. https://doi.org/10.1099/jmm.0.054627-0 CrossRefPubMed

41.

Schlüter A, Nordmann P, Bonnin RA, Millemann Y, Eikmeyer FG, Wibberg D et al (2014) IncH-type plasmid harboring bla _CTX-M-15, bla _DHA-1, and qnrB4 genes recovered from animal isolates. Antimicrob Agents Chemother 58:3768–3773. https://doi.org/10.1128/AAC.02695-14 CrossRefPubMedPubMedCentral

42.

Kis Z, Tóth Á, Jánvári L, Damjanova I (2016) Countrywide dissemination of a DHA-1-type plasmid-mediated AmpC β-lactamase-producing Klebsiella pneumoniae ST11 international high-risk clone in Hungary, 2009-2013. J Med Microbiol 65:1020–1027. https://doi.org/10.1099/jmm.0.000302 CrossRefPubMed

43.

Taniguchi Y, Maeyama Y, Ohsaki Y, Hayashi W, Osaka S, Koide S et al (2017) Co-resistance to colistin and tigecycline by disrupting mgrB and ramR with IS insertions in a canine Klebsiella pneumoniae ST37 isolate producing SHV-12, DHA-1 and FosA3. Int J Antimicrob Agents 50:697–698. https://doi.org/10.1016/j.ijantimicag.2017.09.011 CrossRefPubMed

44.

Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O, Villa L et al (2014) In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 58:3895–3903. https://doi.org/10.1128/AAC.02412-14 CrossRefPubMedPubMedCentral

45.

McArthur AG, Waglechner N, Nizam F, Yan A, Azad MA, Baylay AJ et al (2013) The comprehensive antibiotic resistance database. Antimicrob Agents Chemother 57:3348–3357. https://doi.org/10.1128/AAC.00419-13 CrossRefPubMedPubMedCentral

46.

Wattam AR, Davis JJ, Assaf R, Boisvert S, Brettin T, Bun C et al (2017) Improvements to PATRIC, the all-bacterial bioinformatics database and analysis resource center. Nucleic Acids Res 45:D535–D542. https://doi.org/10.1093/nar/gkw1017 CrossRefPubMed

47.

Darling AE, Mau B, Perna NT (2010) progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 5:e11147. https://doi.org/10.1371/journal.pone.0011147 CrossRefPubMedPubMedCentral

48.

Lawlor MS, O’connor C, Miller VL (2007) Yersiniabactin is a virulence factor for Klebsiella pneumoniae during pulmonary infection. Infect Immun 75:1463–1472. https://doi.org/10.1128/IAI.00372-06 CrossRefPubMedPubMedCentral

49.

Nassif X, Sansonetti PJ (1986) Correlation of the virulence of Klebsiella pneumoniae K1 and K2 with the presence of a plasmid encoding aerobactin. Infect Immun 54:603–608PubMedPubMedCentral

50.

Cheng HY, Chen YS, Wu CY, Chang HY, Lai YC, Peng HL (2010) RmpA regulation of capsular polysaccharide biosynthesis in Klebsiella pneumoniae CG43. J Bacteriol 192:3144–3158. https://doi.org/10.1128/JB.00031-10 CrossRefPubMedPubMedCentral

51.

Carver T, Thomson N, Bleasby A, Berriman M, Parkhill J (2009) DNAPlotter: circular and linear interactive genome visualization. Bioinforma Oxf Engl 25(1):119–120. https://doi.org/10.1093/bioinformatics/btn578 CrossRef

52.

Chérif T, Saidani M, Decré D, Boutiba-Ben Boubaker I, Arlet G (2015) Cooccurrence of multiple AmpC β-lactamases in Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis in Tunisia. Antimicrob Agents Chemother 60:44–51. https://doi.org/10.1128/AAC.00828-15 CrossRefPubMedPubMedCentral

53.

Toleman MA, Bennett PM, Walsh TR (2006) ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev MMBR 70:296–316. https://doi.org/10.1128/MMBR.00048-05 CrossRefPubMed

54.

Cheng C, Sun J, Zheng F, Lu W, Yang Q, Rui Y (2016) New structures simultaneously harboring class 1 integron and ISCR1-linked resistance genes in multidrug-resistant Gram-negative bacteria. BMC Microbiol 16:71. https://doi.org/10.1186/s12866-016-0683-x CrossRefPubMedPubMedCentral

55.

Harmer CJ, Hall RM (2016) IS26-mediated formation of transposons carrying antibiotic resistance genes. mSphere 1. https://doi.org/10.1128/mSphere.00038-16

56.

Hennequin C, Robin F, Cabrolier N, Bonnet R, Forestier C (2012) Characterization of a DHA-1-producing Klebsiella pneumoniae strain involved in an outbreak and role of the AmpR regulator in virulence. Antimicrob Agents Chemother 56:288–294. https://doi.org/10.1128/AAC.00164-11 CrossRefPubMedPubMedCentral

57.

Luk S, Wong W-K, Ho AY-M, Yu KC-H, To W-K, Ng T-K (2016) Clinical features and molecular epidemiology of plasmid-mediated DHA-type AmpC β-lactamase-producing Klebsiella pneumoniae blood culture isolates, Hong Kong. J Glob Antimicrob Resist 7:37–42. https://doi.org/10.1016/j.jgar.2016.06.006 CrossRefPubMed

58.

Ku Y-H, Chuang Y-C, Chen C-C, Lee M-F, Yang Y-C, Tang H-J et al (2017) Klebsiella pneumoniae isolates from meningitis: epidemiology, virulence and antibiotic resistance. Sci Rep 7:6634. https://doi.org/10.1038/s41598-017-06878-6 CrossRefPubMedPubMedCentral

59.

Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L, Delannoy-Vieillard A-S et al (2014) Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis 20:1812–1820. https://doi.org/10.3201/eid2011.140206 CrossRefPubMedPubMedCentral

60.

Cheong HS, Chung DR, Lee C, Kim SH, Kang C-I, Peck KR et al (2016) Emergence of serotype K1 Klebsiella pneumoniae ST23 strains co-producing the plasmid-mediated AmpC beta-lactamase DHA-1 and an extended-spectrum beta-lactamase in Korea. Antimicrob Resist Infect Control 5:50. https://doi.org/10.1186/s13756-016-0151-2 CrossRefPubMedPubMedCentral

Titel: Plasmids carrying DHA-1 β-lactamases
verfasst von: Claire Hennequin
Viviane Ravet
Frédéric Robin
Publikationsdatum: 17.04.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 7/2018
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-018-3231-9

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Plasmids carrying DHA-1 β-lactamases

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