Insights into antimicrobial resistance genotype and potential virulent traits of an extensively drug-resistant <i>Acinetobacter baumannii</i> sequence type ST2

Quang Huy Nguyen; Khanh Linh Hoang; Bich Ngoc Do; Thai Son Nguyen; Thi Thanh Tam Tran

doi:10.15625/vjbt-21792

Author affiliations

Authors

Quang Huy Nguyen $^{1}$ University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam https://orcid.org/0000-0002-3452-1811
Khanh Linh Hoang $^{1}$ University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam https://orcid.org/0009-0003-7276-5408
Bich Ngoc Do $^{1}$ University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
Thai Son Nguyen $^{1}$ University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam https://orcid.org/0009-0007-4415-0819
Thi Thanh Tam Tran $^{1}$ University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam

DOI:

https://doi.org/10.15625/vjbt-21792

Keywords:

Acinetobacter baumannii, extensively drug resistance, antibiotic-resistant genes, sequence type ST2, virulence genes

Abstract

Carbapenem-resistant Acinetobacter baumannii has been ranked as the priority 1 pathogen and is urgently needed for the development of new antimicrobials. Understanding the genetic determinants associated with antibiotic resistance and virulence can help to control the resistant evolution, decide on treatment and have appropriate prevention methods. The present study aimed to characterize the genomic features of an extensively drug-resistant (XDR) A. baumannii sequence type ST2. Phenotypic-drug susceptibility testing was conducted against 28 antibiotics. Whole genome sequencing was performed, followed by an analysis of Clusters of Orthologous Genes (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, multilocus sequence typing (MLST), genetic determinants associated with resistance and virulence, and mobile genetic elements. A. baumannii VD610 was resistant to 26 antibiotics and identified as an extensively antibiotic-resistant phenotype. The genome size of A. baumannii VD610 was 3,765,945 bp, comprising a circular chromosome and two plasmids. The COG annotation identified 3012 genes that could be classified into 22 functional categories. There were 1644 genes mapped to the KEGG pathways. This strain was assigned to the sequence type ST2 by the Pasteur MLST scheme, and harbored 32 antibiotic-resistant genes responsible for aminoglycosides, β-lactams, quinolones, phenicols, tetracyclines, fosfomycins, antifolates, erythromycin, and streptogramin resistance, in which blaOXA-23 and blaOXA-66 are responsible for carbapenem resistance. The virulome of A. baumannii VD610 consists of 36 virulence genes which are crucial for its pathogenicity. Our findings provide the genetic features of Vietnamese XDR A. baumannii sequence type ST2, which can be a reference for further study.

Downloads

References

Abdi, S. N., Ghotaslou, R., Ganbarov, K., Mobed, A., Tanomand, A., Yousefi, et al. (2020). Acinetobacter baumannii efflux pumps and antibiotic resistance. Infection and Drug Resistance, 13, 423-434. https://doi.org/10.2147/IDR.S228089

Alcock, B. P., Raphenya, A. R., Lau, T. T. Y., Tsang, K. K., Bouchard, M., Edalatmand, et al. (2020). CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Research. 48(D1), D517-D525. https://doi.org/10.1093/nar/gkz935

Baleivanualala, S. C., Isaia, L., Devi, S. V., Howden, B., Gorrie, C. L., Matanitobua, et al. (2023). Molecular and clinical epidemiology of carbapenem resistant Acinetobacter baumannii ST2 in Oceania: a multicountry cohort study. The Lancet Regional Health – Western Pacific, 40, 100896. https://doi.org/10.1016/j.lanwpc.2023.100896

Baleivanualala, S. C., Matanitobua, S., Soqo, V., Smita, S., Limaono, J., Sharma, S. C., et al. (2024). Molecular and clinical epidemiology of carbapenem resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales in Fiji: a multicentre prospective observational study. The Lancet Regional Health – Western Pacific, 47, 101095.

https://doi.org/10.1016/j.lanwpc.2024.101095

Bankevich, A., Nurk, S., Antipov, D., Gurevich, A. A., Dvorkin, M., Kulikov, et al. (2012). SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. Journal of Computational Biology, 19(5), 455-477. https://doi.org/10.1089/cmb.2012.0021

Bolger, A. M., Lohse, M., and Usadel, B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics, 30(15), 2114-2120. https://doi.org/10.1093/bioinformatics/btu170

Bortolaia, V., Kaas, R. S., Ruppe, E., Roberts, M. C., Schwarz, S., Cattoir, V., et al. (2020). ResFinder 4.0 for predictions of phenotypes from genotypes. Journal of Antimicrobial Chemotherapy, 75(12), 3491-3500. https://doi.org/10.1093/jac/dkaa345

Chen, L., Yang, J., Yu, J., Yao, Z., Sun, L., Shen, Y., et al. (2005). VFDB: a reference database for bacterial virulence factors. Nucleic Acids Research, 33, D325-328. https://doi.org/10.1093/nar/gki008

Diep, D. T. H., Tuan, H. M., Ngoc, K. M., Vinh, C., Dung, T. T. N., Phat, V. V., et al. (2023). The clinical features and genomic epidemiology of carbapenem-resistant Acinetobacter baumannii infections at a tertiary hospital in Vietnam. Journal of Global Antimicrobial Resistance, 33, 267-275. https://doi.org/10.1016/j.jgar.2023.04.007

Evans, B. A. and Amyes, S. G. (2014). OXA β-lactamases. Clinical Microbiology Reviews, 27(2), 241-263. https://doi.org/10.1128/CMR.00117-13

Grant, J. R., Enns, E., Marinier, E., Mandal, A., Herman, E. K., Chen, C. Y., et al. (2023). Proksee: in-depth characterization and visualization of bacterial genomes. Nucleic Acids Research. 51(W1), W484-W492. https://doi.org/10.1093/nar/gkad326

Gurevich, A., Saveliev, V., Vyahhi, N., and Tesler, G. (2013). QUAST: quality assessment tool for genome assemblies. Bioinformatics, 29(8), 1072-1075. https://doi.org/10.1093/bioinformatics/btt086

Hamidian, M., and Nigro, S. J. (2019). Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii. Microbial Genomics, 5(10), e000306. https://doi.org/10.1099/mgen.0.000306

Hoang, Q. C., Nguyen, T. P. T., Nguyen, D. H., Chan, L. T., Chan, T. T. H., Nguyen, T. S., et al. (2019). Carbapenemase Genes and Multidrug Resistance of Acinetobacter Baumannii: A Cross Sectional Study of Patients with Pneumonia in Southern Vietnam. Antibiotics (Basel), 8(3), 148. https://doi.org/10.3390/antibiotics8030148

Hu, F. P., Guo, Y., Zhu, D. M., Wang, F., Jiang, X. F., Xu, Y. C., et al. (2016). Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. Clinical Microbiology and Infection, 22(1), S9-S14. https://doi.org/10.1016/j.cmi.2016.01.001

Jauneikaite, E., Baker, K. S., Nunn, J. G., Midega, J. T., Hsu, L. Y., Singh, S. R., et al. (2023). Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities. The Lancet Microbe, 4(12), e1040-e1046. https://doi.org/10.1016/S2666-5247(23)00282-3

Johansson, M. H. K., Bortolaia, V., Tansirichaiya, S., Aarestrup, F. M., Roberts, A. P., and Petersen, T. N. (2021). Detection of mobile genetic elements associated with antibiotic resistance in Salmonella enterica using a newly developed web tool: MobileElementFinder. Journal of Antimicrobial Chemotherapy, 76(1), 101-109. https://doi.org/10.1093/jac/dkaa390

Jolley, K. A., Bray, J. E., and Maiden, M. C. J. (2018). Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Research, 3, 124. https://doi.org/10.12688/wellcomeopenres.14826.1

Kanehisa, M., and Goto S. (2000). KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Research, 28(1), 27-30. https://doi.org/10.1093/nar/28.1.27

Khuntayaporn, P., Kanathum, P., Houngsaitong, J., Montakantikul, P., Thirapanmethee, K., and Chomnawang, M. T. (2021). Predominance of international clone 2 multidrug-resistant Acinetobacter baumannii clinical isolates in Thailand: a nationwide study. Annals of Clinical Microbiology and Antimicrobials, 20(1), 19. https://doi.org/10.1186/s12941-021-00424-z

Kumkar, S. N., Kamble, E. E., Chavan, N. S., Dhotre, D. P., and Pardesi, K. R. (2022). Corrigendum: Diversity of resistant determinants, virulence factors, and mobile genetic elements in Acinetobacter baumannii from India: A comprehensive in silico genome analysis. Frontiers in Cellular and Infection Microbiology, 12, 1130394. https://doi.org/10.3389/fcimb.2022.1130394

Le, M. V., Thi, K. N. N., Vinh, P. V., Thompson, C., Huong, L. N. P., Thieu, N. T. V., et al. (2015). In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam. Journal of Medical Microbiology, 64(10), 1162-1169. https://doi.org/10.1099/jmm.0.000137

Leal, N. C., Campos, T. L., Rezende, A. M., Docena, C., Mendes-Marques, C. L., de Sá Cavalcanti, F. L., et al. (2020). Comparative genomics of Acinetobacter baumannii clinical strains from Brazil reveals polyclonal dissemination and selective exchange of mobile genetic elements associated with resistance genes. Frontiers in Microbiology, 11, 1176. https://doi.org/10.3389/fmicb.2020.01176

McCarthy, R. R., Larrouy-Maumus, G. J., Meiqi Tan, M. G. C., and Wareham, D. W. (2021). Antibiotic resistance mechanisms and their transmission in Acinetobacter baumannii. Advances in Experimental Medicine and Biology, 1313, 135-153. https://doi.org/10.1007/978-3-030-67452-6_7

Mirzaei, B., Bazgir, Z. N., Goli, H. R., Iranpour, F., Mohammadi, F., and Babaei, R. (2020). Prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) phenotypes of Pseudomonas aeruginosa and Acinetobacter baumannii isolated in clinical samples from Northeast of Iran. BMC Research Notes, 13(1), 380. https://doi.org/10.1186/s13104-020-05224-w

Morgado, S. M., Fonseca, É. L., Freitas, F. S., Bighi, N. S., Oliveira, P. P. C., Monteiro, P. M., et al. (2024). Outbreak of high-risk XDR CRAB of international clone 2 (IC2) in Rio Janeiro, Brazil. Journal of Global Antimicrobial Resistance, 34, 91-98. https://doi.org/10.1016/j.jgar.2023.06.011

Nowak, J., Zander, E., Stefanik, D., Higgins, P. G., Roca, I., Vila, J., et al. (2017). High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. Journal of Antimicrobial Chemotherapy, 72(12), 3277-3282. https://doi.org/10.1093/jac/dkx322

Popovich, K. J., and Snitkin, E. S. (2017). Whole genome sequencing-implications for infection prevention and outbreak investigations. Current Infectious Disease Reports, 19(4), 15. https://doi.org/10.1007/s11908-017-0570-0

Santajit, S., and Indrawattana N. (2016). Mechanisms of antimicrobial resistance in ESKAPE pathogens. BioMed Research International, 2016, 2475067. https://doi.org/10.1155/2016/2475067

Schwengers, O., Jelonek, L., Dieckmann, M. A., Beyvers, S., Blom, J., and Goesmann, A. (2021). Bakta: rapid and standardized annotation of bacterial genomes via alignment-free sequence identification. Microbial Genomics, 7(11), 000685. https://doi.org/10.1099/mgen.0.000685

Tada, T., Miyoshi-Akiyama, T., Shimada, K., Nga, T. T., Thu, L. T. A., Son, N. T., et al. (2015). Dissemination of clonal complex 2 Acinetobacter baumannii strains co-producing carbapenemases and 16S rRNA methylase ArmA in Vietnam. BMC Infectious Diseases, 15, 433. https://doi.org/10.1186/s12879-015-1171-x

Tada, T., Uchida, H., Hishinuma, T., Watanabe, S., Tohya, M., Kuwahara-Arai, K., et al. (2020). Molecular epidemiology of multidrug-resistant Acinetobacter baumannii isolates from hospitals in Myanmar. Journal of Global Antimicrobial Resistance, 22, 122-125. https://doi.org/10.1016/j.jgar.2020.02.0112020

Nguyen, T. A., Tran, V. T. N, Huynh, M. T., Nguyen S. T., Dao M. Y., Nguyen, V. V. C., et al. (2017). Molecular epidemiology and antimicrobial resistance phenotypes of Acinetobacter baumannii isolated from patients in three hospitals in southern Vietnam. Journal of Medical Microbiology, 66 (1), 46-53. https://doi.org/10.1099/jmm.0.000418

Upmanyu, K., Haq, Q. M. R., and Singh, R. (2022). Factors mediating Acinetobacter baumannii biofilm formation: Opportunities for developing therapeutics. Current Research in Microbial Sciences, 3, 100131. https://doi.org/10.1016/j.crmicr.2022.100131

Verma, P., Tiwari, M., and Tiwari, V. (2021). Efflux pumps in multidrug-resistant Acinetobacter baumannii: Current status and challenges in the discovery of efflux pumps inhibitors. Microbial Pathogenesis, 152, 104766. https://doi.org/10.1016/j.micpath.2021.104766

Zarrilli, R., Pournaras, S., Giannouli, M., and Tsakris, A. (2013). Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. International Journal of Antimicrobial Agents, 41(1), 11-19. https://doi.org/10.1016/j.ijantimicag.2012.09.008