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10.06.2024 | Research

Genetic basis of antimicrobial resistance, virulence features and phylogenomics of carbapenem-resistant Acinetobacter baumannii clinical isolates

verfasst von: Bojana Lukovic, Jovana Kabic, Milan Dragicevic, Sonja Kuljanin, Ivica Dimkic, Branko Jovcic, Ina Gajic

Erschienen in: Infection

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Abstract

Purpose

The worldwide emergence and clonal spread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern. In the present study, we determined the mechanisms of antimicrobial resistance, virulence gene repertoire and genomic relatedness of CRAB isolates circulating in Serbian hospitals.

Methods

CRAB isolates were analyzed using whole-genome sequencing (WGS) for the presence of antimicrobial resistance-encoding genes, virulence factors-encoding genes, mobile genetic elements and genomic relatedness. Antimicrobial susceptibility testing was done by disk diffusion and broth microdilution methods.

Results

Eleven isolates exhibited an MDR resistance phenotype, while four of them were XDR. MIC₉₀ for meropenem and imipenem were > 64 µg/mL and 32 µg/mL, respectively. While all CRABs harbored bla_OXA−66 variant of bla_OXA−51 gene, those assigned to ST^Pas2, ST^Pas636 and ST^Pas492 had bla_ADC−73,bla_ADC−74 and bla_ADC−30 variants, respectively. The following acquired carbapenemases-encoding genes were found: bla_OXA−72 (n = 12), bla_OXA−23 (n = 3), and bla_NDM−1(n = 5), and were mapped to defined mobile genetic elements. MLST analysis assigned the analyzed CRAB isolates to three Pasteur sequence types (STs): ST^Pas2, ST^Pas492, and ST^Pas636. The Majority of strains belonged to International Clone II (ICII) and carried tested virulence-related genes liable for adherence, biofilm formation, iron uptake, heme biosynthesis, zinc utilization, serum resistance, stress adaptation, intracellular survival and toxin activity.

Conclusion

WGS elucidated the resistance and virulence profiles of CRABs isolated from clinical samples in Serbian hospitals and genomic relatedness of CRAB isolates from Serbia and globally distributed CRABs.

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Nguyen M, Joshi SG. Carbapenem resistance in Acinetobacter baumannii, and their importance in hospital-acquired infections: a scientific review. J Appl Microbiol. 2021;131(6):2715–38. https://doi.org/10.1111/jam.15130.CrossRefPubMed

Xie R, Zhang XD, Zhao Q, Peng B, Zheng J. Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries. Emerg Microbes Infect. 2018;7(1):31. https://doi.org/10.1038/s41426-018-0038-9.CrossRefPubMedPubMedCentral

Dortet L, Bonnin RA, Bernabeu S, Escaut L, Vittecoq D, Girlich D, et al. First occurrence of OXA-72-Producing Acinetobacter baumannii in Serbia. Antimicrob Agents Chemother. 2016;60(10):5724–30. https://doi.org/10.1128/AAC.01016-16.CrossRefPubMedPubMedCentral

Pfeifer Y, Wilharm G, Zander E, Wichelhaus TA, Göttig S, Hunfeld KP, et al. Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007. J Antimicrob Chemother. 2011;66(9):1998–2001. https://doi.org/10.1093/jac/dkr256.CrossRefPubMed

Zarrilli R, Pournaras S, Giannouli M, Tsakris A. Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. Int J Antimicrob Agents. 2013;41(1):11–9. https://doi.org/10.1016/j.ijantimicag.2012.09.008.CrossRefPubMed

Fitzpatrick MA, Ozer EA, Hauser AR. Utility of whole-genome sequencing in characterizing Acinetobacter epidemiology and analyzing Hospital outbreaks. J Clin Microbiol. 2016;54(3):593–612. https://doi.org/10.1128/JCM.01818-15.CrossRefPubMedPubMedCentral

Performance Standards for Antimicrobial Susceptibility Testing. Twenty-seventh informational supplement M100-S27. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.

Breakpoint tables for interpretation. Of MICs and zone diameters. Version 8.1. European Committee on Antimicrobial Susceptibility Testing; 2018.

Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–81. https://doi.org/10.1111/j.1469-0691.2011.03570.x.CrossRefPubMed

10.

Andrews S. Babraham Bioinformatics - FastQC A Quality Control tool for High Throughput Sequence Data, 2010. https://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (Accessed May 29, 2023).

11.

Prjibelski A, Antipov D, Meleshko D, Lapidus A, Korobeynikov A. Using SPAdes De Novo Assembler. Curr Protoc Bioinf. 2020;70(1):e102. https://doi.org/10.1002/cpbi.102.CrossRef

12.

Simão FA, Waterhouse RM, Ioannidis P, Kriventseva EV, Zdobnov EM. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics. 2015;31(19):3210–2. https://doi.org/10.1093/bioinformatics/btv351.CrossRefPubMed

13.

Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30(14):2068–9. https://doi.org/10.1093/bioinformatics/btu153.CrossRefPubMed

14.

Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M, Edalatmand A, et al. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 2020;48(D1):D517–25. https://doi.org/10.1093/nar/gkz935.CrossRefPubMed

15.

Liu B, Zheng D, Zhou S, Chen L, Yang J. VFDB 2022: a general classification scheme for bacterial virulence factors. Nucleic Acids Res. 2022;50(D1):D912–7. https://doi.org/10.1093/nar/gkab1107.CrossRefPubMed

16.

Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res. 2006;34(Database issue):D32–6. https://doi.org/10.1093/nar/gkj014.CrossRefPubMed

17.

Yoon SH, Park YK, Kim JF. PAIDB v2.0: exploration and analysis of pathogenicity and resistance islands. Nucleic Acids Res. 2015;43(Database issue):D624–30. https://doi.org/10.1093/nar/gku985.CrossRefPubMed

18.

Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S, Holden MT, et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics. 2015;31(22):3691–3. https://doi.org/10.1093/bioinformatics/btv421.CrossRefPubMedPubMedCentral

19.

Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T, Keane JA, et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom. 2016;2(4):e000056. https://doi.org/10.1099/mgen.0.000056.CrossRefPubMedPubMedCentral

20.

Stamatakis A. Bioinformatics. 2014;30(9):1312–3. https://doi.org/10.1093/bioinformatics/btu033. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies.

21.

Letunic I, Bork P. Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 2021;49(W1):W293–6. https://doi.org/10.1093/nar/gkab301.CrossRefPubMedPubMedCentral

22.

Jolley KA, Bray JE, Maiden MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018;3:124. https://doi.org/10.12688/wellcomeopenres.14826.1.CrossRefPubMedPubMedCentral

23.

Asnicar F, Thomas AM, Beghini F, Mengoni C, Manara S, Manghi P, et al. Precise phylogenetic analysis of microbial isolates and genomes from metagenomes using PhyloPhlAn 3.0. Nat Commun. 2020;11(1):2500. https://doi.org/10.1038/s41467-020-16366-7.CrossRefPubMedPubMedCentral

24.

Revell LJ. Phytools: an R package for phylogenetic comparative biology (and other things). Methods Ecol Evol. 2012;3(2):217–23. https://doi.org/10.1111/j.2041-210X.2011.00169.CrossRef

25.

Chen CH, Kuo HY, Hsu PJ, Chang CM, Chen JY, Lu HH, et al. Clonal spread of carbapenem-resistant Acinetobacter baumannii across a community hospital and its affiliated long-term care facilities: a cross sectional study. J Microbiol Immunol Infect. 2018;51(3):377–84. https://doi.org/10.1016/j.jmii.2017.08.001.CrossRefPubMed

26.

Havenga B, Ndlovu T, Clements T, Reyneke B, Waso M, Khan W. Exploring the antimicrobial resistance profiles of WHO critical priority list bacterial strains. BMC Microbiol. 2019;19(1):303. https://doi.org/10.1186/s12866-019-1687-0.CrossRefPubMedPubMedCentral

27.

Asadian M, Azimi L, Alinejad F, Ostadi Y, Lari AR. Molecular characterization of Acinetobacter baumannii isolated from Ventilator-Associated Pneumonia and burn Wound colonization by Random amplified polymorphic DNA polymerase chain reaction and the relationship between Antibiotic susceptibility and Biofilm Production. Adv Biomed Res. 2019;8:58. https://doi.org/10.4103/abr.abr_256_18.CrossRefPubMedPubMedCentral

28.

Kostyanev T, Xavier BB, García-Castillo M, Lammens C, Bravo-Ferrer Acosta J, Rodríguez-Baño J, et al. Phenotypic and molecular characterizations of carbapenem-resistant Acinetobacter baumannii isolates collected within the EURECA study. Int J Antimicrob Agents. 2021;57(6):106345. https://doi.org/10.1016/j.ijantimicag.2021.106345.CrossRefPubMed

29.

Weber RE, Pietsch M, Frühauf A, Pfeifer Y, Martin M, Luft D, et al. IS26-Mediated transfer of bla_NDM-1 as the Main Route of Resistance Transmission during a polyclonal, multispecies Outbreak in a German hospital. Front Microbiol. 2019;10:2817. https://doi.org/10.3389/fmicb.2019.02817.CrossRefPubMedPubMedCentral

30.

Samuelsen Ø, Overballe-Petersen S, Bjørnholt JV, Brisse S, Doumith M, Woodford N, et al. Molecular and epidemiological characterization of carbapenemase-producing Enterobacteriaceae in Norway, 2007 to 2014. PLoS ONE. 2017;12(11):e0187832. https://doi.org/10.1371/journal.pone.0187832.CrossRefPubMedPubMedCentral

31.

Ambrose SJ, Hamidian M, Hall RM. Extensively resistant Acinetobacter baumannii isolate RCH52 carries several resistance genes derived from an IncC plasmid. J Antimicrob Chemother. 2022;77(4):930–3. https://doi.org/10.1093/jac/dkab473.CrossRefPubMed

32.

Vijayakumar S, Jacob JJ, Vasudevan K, Mathur P, Ray P, Neeravi A, et al. Genomic characterization of Mobile Genetic Elements Associated with Carbapenem Resistance of Acinetobacter baumannii from India. Front Microbiol. 2022;13:869653. https://doi.org/10.3389/fmicb.2022.869653.CrossRefPubMedPubMedCentral

33.

Karah N, Sundsfjord A, Towner K, Samuelsen Ø. Insights into the global molecular epidemiology of carbapenem non-susceptible clones of Acinetobacter baumannii. Drug Resist Updat. 2012;15(4):237–47. https://doi.org/10.1016/j.drup.2012.06.001.CrossRefPubMed

34.

Mugnier PD, Poirel L, Naas T, Nordmann P. Worldwide dissemination of the blaOXA-23 carbapenemase gene of Acinetobacter baumannii. Emerg Infect Dis. 2010;16(1):35–40. https://doi.org/10.3201/eid1601.090852.CrossRefPubMedPubMedCentral

35.

Al Atrouni A, Hamze M, Jisr T, Lemarié C, Eveillard M, Joly-Guillou ML, et al. Wide spread of OXA-23-producing carbapenem-resistant Acinetobacter baumannii belonging to clonal complex II in different hospitals in Lebanon. Int J Infect Dis. 2016;52:29–36. https://doi.org/10.1016/j.ijid.2016.09.017.CrossRefPubMed

36.

Eigenbrod T, Reuter S, Gross A, Kocer K, Günther F, Zimmermann S, et al. Molecular characterization of carbapenem-resistant Acinetobacter baumannii using WGS revealed missed transmission events in Germany from 2012-15. J Antimicrob Chemother. 2019;74(12):3473–80. https://doi.org/10.1093/jac/dkz360.CrossRefPubMed

37.

Karah N, Dwibedi CK, Sjöström K, Edquist P, Johansson A, Wai SN, et al. Novel Aminoglycoside Resistance transposons and Transposon-Derived circular forms detected in Carbapenem-Resistant Acinetobacter baumannii Clinical isolates. Antimicrob Agents Chemother. 2016;60(3):1801–18. https://doi.org/10.1128/AAC.02143-15.CrossRefPubMedPubMedCentral

38.

Lucidi M, Visaggio D, Migliaccio A, Capecchi G, Visca P, Imperi F, et al. Pathogenicity and virulence of Acinetobacter baumannii: factors contributing to the fitness in healthcare settings and the infected host. Virulence. 2024;15(1):2289769. https://doi.org/10.1080/21505594.2023.2289769.CrossRefPubMed

39.

Makke G, Bitar I, Salloum T, Panossian B, Alousi S, Arabaghian H, et al. Whole-genome-sequence-based characterization of extensively drug-resistant Acinetobacter baumannii Hospital Outbreak. mSphere. 2020;5(1):e00934–19. https://doi.org/10.1128/mSphere.00934-19.CrossRefPubMedPubMedCentral

40.

Osman M, Halimeh B, Rafei F, Mallat R, Tom H, Raad JE. Investigation of an XDR-Acinetobacter baumannii ST2 outbreak in an intensive care unit of a Lebanese tertiary care hospital. Future Microbiol. 2020;15:1535–42. https://doi.org/10.2217/fmb-2020-0079.CrossRefPubMed

Titel: Genetic basis of antimicrobial resistance, virulence features and phylogenomics of carbapenem-resistant Acinetobacter baumannii clinical isolates
verfasst von: Bojana Lukovic
Jovana Kabic
Milan Dragicevic
Sonja Kuljanin
Ivica Dimkic
Branko Jovcic
Ina Gajic
Publikationsdatum: 10.06.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Infection
Print ISSN: 0300-8126
Elektronische ISSN: 1439-0973
DOI: https://doi.org/10.1007/s15010-024-02316-8

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