A Novel Bacteroides Metallo-β-lactamase (MBL) and Its Gene (crxA) in Bacteroides Xylanisolvens Revealed by Genomic Sequencing and Functional Analysis

Overview

Journal J Antimicrob Chemother

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2022 Mar 17

PMID 35296904

Authors

Jozsef Soki

Uwe Lang

Ulrike Schumacher

Istvan Nagy

Agnes Berenyi

Tamas Feher

Katalin Burian

Elisabeth Nagy

Affiliations

Soon will be listed here.

Abstract

Objectives: We sought to characterize the carbapenem resistance mechanism of Bacteroides xylanisolvens 14880, an imipenem-resistant strain from Germany, and assess its prevalence.

Methods: Antimicrobial susceptibilities were determined using agar dilution or Etest methodology and specific imipenemase activity was detected. The genomic sequence of B. xylanisolvens 14880 was determined and analysed for antibiotic resistance genes and genomic islands. We also used gene transfer to a carbapenem susceptible host, along with 5'-RACE, conventional PCR with capillary sequencing and RT-PCR-based screening.

Results: B. xylanisolvens 14880 displayed resistance to carbapenems and produced high specific imipenemase activity. Its genomic sequence was 6.1 Mbp and a class B1 β-lactamase gene (termed crxA) was detected in it. crxA was carried on a putative genomic island with insertion sequence (IS) elements and a putative GNAT (Gcn5-like acetyltransferase) toxin gene. Promoter localization by 5'-RACE and gene targeting to an imipenem-susceptible Bacteroides host indicated that it is activated by an IS1380-like IS element and it can confer carbapenem resistance. The PCR screening of Bacteroides strains showed that crxA was specific to B. xylanisolvens with a carriage rate of 16.7%.

Conclusions: B. xylanisolvens strains can harbour a carbapenem resistance gene, which has many similarities to the 'cfiA system': metallo-β-lactamase (MBL), IS element activation, carriage of a GNAT toxin gene, specific for a unique Bacteroides species with a significant prevalence.

Citing Articles

Detection of the antibiotic resistance genes content of intestinal Bacteroides, Parabacteroides and Phocaeicola isolates from healthy and carbapenem-treated patients from European countries.

Soki J, Wybo I, Baaity Z, Stefan G, Jeverica S, Ulger N BMC Microbiol. 2024; 24(1):202.

PMID: 38851699 PMC: 11162026. DOI: 10.1186/s12866-024-03354-w.

Strategies to Name Metallo-β-Lactamases and Number Their Amino Acid Residues.

Oelschlaeger P, Kaadan H, Dhungana R Antibiotics (Basel). 2023; 12(12).

PMID: 38136780 PMC: 10740994. DOI: 10.3390/antibiotics12121746.

Recent Trends in Antimicrobial Resistance among Anaerobic Clinical Isolates.

Reissier S, Penven M, Guerin F, Cattoir V Microorganisms. 2023; 11(6).

PMID: 37374976 PMC: 10302625. DOI: 10.3390/microorganisms11061474.

References

Snydman D, Jacobus N, McDermott L, Ruthazer R, Golan Y, Goldstein E . National survey on the susceptibility of Bacteroides fragilis group: report and analysis of trends in the United States from 1997 to 2004. Antimicrob Agents Chemother. 2007; 51(5):1649-55. PMC: 1855532. DOI: 10.1128/AAC.01435-06. View

Sarvari K, Soki J, Kristof K, Juhasz E, Miszti C, Latkoczy K . A multicentre survey of the antibiotic susceptibility of clinical Bacteroides species from Hungary. Infect Dis (Lond). 2018; 50(5):372-380. DOI: 10.1080/23744235.2017.1418530. View

Hurlbut S, Cuchural G, Tally F . Imipenem resistance in Bacteroides distasonis mediated by a novel beta-lactamase. Antimicrob Agents Chemother. 1990; 34(1):117-20. PMC: 171531. DOI: 10.1128/AAC.34.1.117. View

Chassard C, Delmas E, Lawson P, Bernalier-Donadille A . Bacteroides xylanisolvens sp. nov., a xylan-degrading bacterium isolated from human faeces. Int J Syst Evol Microbiol. 2008; 58(Pt 4):1008-13. DOI: 10.1099/ijs.0.65504-0. View

Sadarangani S, Cunningham S, Jeraldo P, Wilson J, Khare R, Patel R . Metronidazole- and carbapenem-resistant bacteroides thetaiotaomicron isolated in Rochester, Minnesota, in 2014. Antimicrob Agents Chemother. 2015; 59(7):4157-61. PMC: 4468676. DOI: 10.1128/AAC.00677-15. View

Soki J, Wybo I, Hajdu E, Ulger Toprak N, Jeverica S, Stingu C . A Europe-wide assessment of antibiotic resistance rates in Bacteroides and Parabacteroides isolates from intestinal microbiota of healthy subjects. Anaerobe. 2020; 62:102182. DOI: 10.1016/j.anaerobe.2020.102182. View

Bortolaia V, Kaas R, Ruppe E, Roberts M, Schwarz S, Cattoir V . ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother. 2020; 75(12):3491-3500. PMC: 7662176. DOI: 10.1093/jac/dkaa345. View

Hansen K, Schwensen S, Henriksen D, Justesen U, Sydenham T . Antimicrobial resistance in the Bacteroides fragilis group in faecal samples from patients receiving broad-spectrum antibiotics. Anaerobe. 2017; 47:79-85. DOI: 10.1016/j.anaerobe.2017.04.013. View

Smith C, Rollins L, Parker A . Nucleotide sequence determination and genetic analysis of the Bacteroides plasmid, pBI143. Plasmid. 1995; 34(3):211-22. DOI: 10.1006/plas.1995.0007. View

10.

Wexler H . Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007; 20(4):593-621. PMC: 2176045. DOI: 10.1128/CMR.00008-07. View

11.

Pedersen R, Marmolin E, Justesen U . Species differentiation of Bacteroides dorei from Bacteroides vulgatus and Bacteroides ovatus from Bacteroides xylanisolvens - back to basics. Anaerobe. 2013; 24:1-3. DOI: 10.1016/j.anaerobe.2013.08.004. View

12.

Bertelli C, Laird M, Williams K, Lau B, Hoad G, Winsor G . IslandViewer 4: expanded prediction of genomic islands for larger-scale datasets. Nucleic Acids Res. 2017; 45(W1):W30-W35. PMC: 5570257. DOI: 10.1093/nar/gkx343. View

13.

Jurenas D, Garcia-Pino A, Van Melderen L . Novel toxins from type II toxin-antitoxin systems with acetyltransferase activity. Plasmid. 2017; 93:30-35. DOI: 10.1016/j.plasmid.2017.08.005. View

14.

Kaeuffer C, Ruge T, Diancourt L, Romain B, Ruch Y, Jaulhac B . First Case of Bacteraemia Due to Carbapenem-Resistant . Antibiotics (Basel). 2021; 10(3). PMC: 8003481. DOI: 10.3390/antibiotics10030319. View

15.

Concha N, Rasmussen B, Bush K, Herzberg O . Crystal structure of the wide-spectrum binuclear zinc beta-lactamase from Bacteroides fragilis. Structure. 1996; 4(7):823-36. DOI: 10.1016/s0969-2126(96)00089-5. View

16.

Garcia N, Gutierrez G, Lorenzo M, Vadillo S, Piriz S, Quesada A . Gene Context and DNA rearrangements in the carbapenemase locus of division II strains of Bacteroides fragilis. Antimicrob Agents Chemother. 2009; 53(6):2677-8. PMC: 2687242. DOI: 10.1128/AAC.01514-08. View

17.

Soki J, Edwards R, Urban E, Fodor E, Beer Z, Nagy E . Screening of isolates from faeces for carbapenem-resistant Bacteroides strains; existence of strains with novel types of resistance mechanisms. Int J Antimicrob Agents. 2004; 24(5):450-4. DOI: 10.1016/j.ijantimicag.2004.06.017. View

18.

Soki J, Hedberg M, Patrick S, Balint B, Herczeg R, Nagy I . Emergence and evolution of an international cluster of MDR Bacteroides fragilis isolates. J Antimicrob Chemother. 2016; 71(9):2441-8. DOI: 10.1093/jac/dkw175. View