Genetic Basis of Antimicrobial Resistance, Virulence Features and Phylogenomics of Carbapenem-resistant Acinetobacter Baumannii Clinical Isolates

Overview

Journal Infection

Date 2024 Jun 10

PMID 38856809

Authors

Bojana Lukovic

Jovana Kabic

Milan Dragicevic

Sonja Kuljanin

Ivica Dimkic

Branko Jovcic

Ina Gajic

Affiliations

Soon will be listed here.

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. MIC for meropenem and imipenem were > 64 µg/mL and 32 µg/mL, respectively. While all CRABs harbored bla variant of bla gene, those assigned to ST2, ST636 and ST492 had blabla and bla variants, respectively. The following acquired carbapenemases-encoding genes were found: bla (n = 12), bla (n = 3), and bla(n = 5), and were mapped to defined mobile genetic elements. MLST analysis assigned the analyzed CRAB isolates to three Pasteur sequence types (STs): ST2, ST492, and ST636. 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.

Citing Articles

Molecular Epidemiology and Genetic Characterization of Carbapenem-Resistant Isolates from the ICU of a Tertiary Hospital in East China.

Liu L, Huang Y, Wang Y, Jiang Y, Liu K, Pei Z Infect Drug Resist. 2025; 17:5925-5945.

PMID: 39759767 PMC: 11699857. DOI: 10.2147/IDR.S491858.

Cefiderocol-Based Regimen for Acinetobacter NDM-1 Outbreak.

Travi G, Peracchi F, Merli M, Lo Re N, Matarazzo E, Tartaglione L Antibiotics (Basel). 2024; 13(8).

PMID: 39200070 PMC: 11350908. DOI: 10.3390/antibiotics13080770.

References

Nguyen M, Joshi S . Carbapenem resistance in Acinetobacter baumannii, and their importance in hospital-acquired infections: a scientific review. J Appl Microbiol. 2021; 131(6):2715-2738. DOI: 10.1111/jam.15130. View

Xie R, Zhang X, 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. PMC: 5849731. DOI: 10.1038/s41426-018-0038-9. View

Dortet L, Bonnin R, Bernabeu S, Escaut L, Vittecoq D, Girlich D . First Occurrence of OXA-72-Producing Acinetobacter baumannii in Serbia. Antimicrob Agents Chemother. 2016; 60(10):5724-30. PMC: 5038319. DOI: 10.1128/AAC.01016-16. View

Pfeifer Y, Wilharm G, Zander E, Wichelhaus T, Gottig S, Hunfeld K . Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007. J Antimicrob Chemother. 2011; 66(9):1998-2001. DOI: 10.1093/jac/dkr256. View

Zarrilli R, Pournaras S, Giannouli M, Tsakris A . Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. Int J Antimicrob Agents. 2012; 41(1):11-9. DOI: 10.1016/j.ijantimicag.2012.09.008. View

Fitzpatrick M, Ozer E, Hauser A . Utility of Whole-Genome Sequencing in Characterizing Acinetobacter Epidemiology and Analyzing Hospital Outbreaks. J Clin Microbiol. 2015; 54(3):593-612. PMC: 4767972. DOI: 10.1128/JCM.01818-15. View

Magiorakos A, Srinivasan A, Carey R, Carmeli Y, Falagas M, Giske C . Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2011; 18(3):268-81. DOI: 10.1111/j.1469-0691.2011.03570.x. View

Simao F, Waterhouse R, Ioannidis P, Kriventseva E, Zdobnov E . BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics. 2015; 31(19):3210-2. DOI: 10.1093/bioinformatics/btv351. View

Seemann T . Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014; 30(14):2068-9. DOI: 10.1093/bioinformatics/btu153. View

10.

Alcock B, Raphenya A, Lau T, Tsang K, Bouchard M, Edalatmand A . CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 2019; 48(D1):D517-D525. PMC: 7145624. DOI: 10.1093/nar/gkz935. View

11.

Liu B, Zheng D, Zhou S, Chen L, Yang J . VFDB 2022: a general classification scheme for bacterial virulence factors. Nucleic Acids Res. 2021; 50(D1):D912-D917. PMC: 8728188. DOI: 10.1093/nar/gkab1107. View

12.

Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M . ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res. 2005; 34(Database issue):D32-6. PMC: 1347377. DOI: 10.1093/nar/gkj014. View

13.

Yoon S, Park Y, Kim J . PAIDB v2.0: exploration and analysis of pathogenicity and resistance islands. Nucleic Acids Res. 2014; 43(Database issue):D624-30. PMC: 4384037. DOI: 10.1093/nar/gku985. View

14.

Page A, Cummins C, Hunt M, Wong V, Reuter S, Holden M . Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics. 2015; 31(22):3691-3. PMC: 4817141. DOI: 10.1093/bioinformatics/btv421. View

15.

Page A, Taylor B, Delaney A, Soares J, Seemann T, Keane J . : rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom. 2017; 2(4):e000056. PMC: 5320690. DOI: 10.1099/mgen.0.000056. View

16.

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-W296. PMC: 8265157. DOI: 10.1093/nar/gkab301. View

17.

Jolley K, Bray J, Maiden M . Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018; 3:124. PMC: 6192448. DOI: 10.12688/wellcomeopenres.14826.1. View

18.

Asnicar F, Thomas A, Beghini F, Mengoni C, Manara S, Manghi P . Precise phylogenetic analysis of microbial isolates and genomes from metagenomes using PhyloPhlAn 3.0. Nat Commun. 2020; 11(1):2500. PMC: 7237447. DOI: 10.1038/s41467-020-16366-7. View

19.

Chen C, Kuo H, Hsu P, Chang C, Chen J, Lu H . 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. 2017; 51(3):377-384. DOI: 10.1016/j.jmii.2017.08.001. View

20.

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. PMC: 6929480. DOI: 10.1186/s12866-019-1687-0. View