ANALYSIS OF ACQUIRED ANTIMICROBIAL RESISTANCE GENES IN GENOMES OF IRAQI ACINETOBACTER BAUMANNII
Downloads
Objective: This study aimed to investigate and analyze antimicrobial-resistant (AMR) genes in Acinetobacter baumannii isolates from Iraq, identify the frequency and proportions of resistant genes, and determine strains resistant to multiple antibiotics, including their genetic profiles based on protein-coded gene sequences. Methods: A total of 41 A. baumannii draft genome sequences were retrieved from the PATRIC database, spanning 2004–2018, and analyzed using ResFinder 4.0 for antibiotic resistance genes. Molecular typing was conducted via the Pasture MLST scheme targeting seven housekeeping genes (e.g., cpn60, fusA). Data were processed through the Center for Genomic Epidemiology for detailed resistance profiling. Results: Fifty-two known resistance genes were identified in 41 genomes. Most strains demonstrated multidrug resistance (MDR), while one strain exhibited extensive drug resistance (XDR). These findings underscore the concerning emergence of highly resistant A. baumannii strains in Iraq. Novelty: The study validates ResFinder 4.0 as an effective in silico tool for genetic analysis of AMR genes in A. baumannii, providing a comprehensive genomic epidemiological profile of Iraqi isolates. This is among the first studies to offer such detailed insights into the genetic resistance mechanisms of A. baumannii in Iraq.
J. O'Neill, "Tackling drug-resistant infections globally: final report and recommendations," 2016.
Centers for Disease Control and Prevention, "Antibiotic resistance threats in the United States, 2013," Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA, 2013. [Online]. Available: https://www.cdc.gov/drugresistance/threat-report-2013/pdf/arthreats-2013-508.pdf.
A. Monserrat-Martinez, Y. Gambin, and E. Sierecki, "Thinking outside the bug: molecular targets and strategies to overcome antibiotic resistance," International Journal of Molecular Sciences, vol. 20, no. 6, p. 1255, 2019.
G. M. Eliopoulos, L. L. Maragakis, and T. M. Perl, "Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options," Clinical Infectious Diseases, vol. 46, no. 8, pp. 1254–1263, 2008.
V. Manchanda, S. Sanchaita, and N. P. Singh, "Multidrug-resistant Acinetobacter," Journal of Global Infectious Diseases, vol. 2, no. 3, p. 291, 2010.
S. Hernando-Amado, T. M. Coque, F. Baquero, and J. L. Martínez, "Defining and combating antibiotic resistance from One Health and Global Health perspectives," Nature Microbiology, vol. 4, no. 9, pp. 1432–1442, 2019.
C. J. Murray, K. S. Ikuta, F. Sharara, L. Swetschinski, G. R. Aguilar, A. Gray, ... and N. Tasak, "Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis," The Lancet, vol. 399, no. 10325, pp. 629–655, 2022.
E. C. Eze, H. Y. Chenia, and M. E. El Zowalaty, "Acinetobacter baumannii biofilms: effects of physicochemical factors, virulence, antibiotic resistance determinants, gene regulation, and future antimicrobial treatments," Infection and Drug Resistance, vol. 11, pp. 2277–2297, 2018.
L. Dijkshoorn, A. Nemec, and H. Seifert, "An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii," Nature Reviews Microbiology, vol. 5, no. 12, pp. 939–951, 2007.
X. Didelot, A. S. Walker, T. E. Peto, D. W. Crook, and D. J. Wilson, "Within-host evolution of bacterial pathogens," Nature Reviews Microbiology, vol. 14, no. 3, pp. 150–162, 2016.
WHO, "Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics," 2017. [Online]. Available: https://www.who.int/medicines/areas/rational_use/prioritization-of-pathogens/en/.
E. Tacconelli, E. Carrara, A. Savoldi, S. Harbarth, M. Mendelson, D. L. Monnet, ... and A. Zorzet, "Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis," The Lancet Infectious Diseases, vol. 18, no. 3, pp. 318–327, 2018.
A. A. Shali, P. J. Jalal, and S. K. Arif, "Dissemination and genetic relatedness of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii isolates from a burn hospital in Iraq," Canadian Journal of Infectious Diseases and Medical Microbiology, vol. 2022, pp. 1–10, 2022.
M. Pagano, A. F. Martins, and A. L. Barth, "Mobile genetic elements related to carbapenem resistance in Acinetobacter baumannii," Brazilian Journal of Microbiology, vol. 47, pp. 785–792, 2016.
M. Z. Al-Hasso and S. H. Khalaf, "Comparison of five methods for detection of extended spectrum β-lactamases in Gram negative enteric bacteria," Karbala International Journal of Modern Science, vol. 6, no. 1, pp. 9–15, 2020.
K. Bush and P. A. Bradford, "β-Lactams and β-lactamase inhibitors: an overview," Cold Spring Harbor Perspectives in Medicine, vol. 6, no. 8, pp. a025247, 2016.
Y. Pfeifer, K. P. Hunfeld, S. Borgmann, D. Maneg, W. Blobner, G. Werner, and P. G. Higgins, "Carbapenem-resistant Acinetobacter baumannii ST78 with OXA-72 carbapenemase and ESBL gene bla CTX-M-115," Journal of Antimicrobial Chemotherapy, vol. 71, no. 5, pp. 1426–1428, 2016.
A. Khondker and M. C. Rheinstädter, "How do bacterial membranes resist polymyxin antibiotics?," Communications Biology, vol. 3, no. 1, pp. 1–4, 2020.
S. Bakour, A. O. Olaitan, H. Ammari, A. Touati, S. Saoudi, K. Saoudi, and J. M. Rolain, "Emergence of colistin-and carbapenem-resistant Acinetobacter baumannii ST2 clinical isolate in Algeria: first case report," Microbial Drug Resistance, vol. 21, no. 3, pp. 279–285, 2015.
N. Thadtapong, S. Chaturongakul, S. Soodvilai, and P. Dubbs, "Colistin and carbapenem-resistant Acinetobacter baumannii Aci46 in Thailand: genome analysis and antibiotic resistance profiling," Antibiotics, vol. 10, no. 9, p. 1054, 2021.
C. Hahm, H. S. Chung, and M. Lee, "Whole-genome sequencing for the characterization of resistance mechanisms and epidemiology of colistin-resistant Acinetobacter baumannii," PLoS One, vol. 17, no. 3, p. e0264335, 2022.
R. A. Moghnieh, J. A. Moussa, M. A. Aziz, and G. M. Matar, "Phenotypic and genotypic characterisation of cephalosporin-, carbapenem-and colistin-resistant Gram-negative bacterial pathogens in Lebanon, Jordan and Iraq," J. Glob. Antimicrob. Resist., vol. 27, pp. 175–199, 2021.
J. H. Moffatt et al., "Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production," Antimicrob. Agents Chemother., vol. 54, no. 12, pp. 4971–4977, 2010.
L. Poirel et al., "The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae," J. Antimicrob. Chemother., vol. 70, no. 1, pp. 75–80, 2015.
J. J. Davis et al., "The PATRIC Bioinformatics Resource Center: expanding data and analysis capabilities," Nucleic Acids Res., vol. 48, no. D1, pp. D606–D612, 2020.
V. Bortolaia et al., "ResFinder 4.0 for predictions of phenotypes from genotypes," J. Antimicrob. Chemother., vol. 75, no. 12, pp. 3491–3500, 2020.
L. Diancourt, V. Passet, A. Nemec, L. Dijkshoorn, and S. Brisse, "The population structure of Acinetobacter baumannii: expanding multiresistant clones from an ancestral susceptible genetic pool," PLoS One, vol. 5, no. 4, p. e10034, 2010.
K. A. Jolley, J. E. Bray, and M. C. Maiden, "Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications," Wellcome Open Res., vol. 3, 2018.
J. Pendleton, S. Gorman, and B. Gilmore, "Clinical relevance of the ESKAPE pathogens," Expert Rev. Anti Infect. Ther., vol. 11, pp. 297–308, 2013.
L. Guo et al., "Clinical features predicting mortality risk in patients with viral pneumonia: the MuLBSTA score," Front. Microbiol., vol. 10, p. 476945, 2019.
J. Mancilla-Rojano et al., "Whole-genome sequences of five Acinetobacter baumannii strains from a child with leukemia M2," Front. Microbiol., vol. 10, p. 423395, 2019.
R. Saranathan et al., "Multiple drug-resistant carbapenemases producing Acinetobacter baumannii isolates harbor multiple R-plasmids," Indian J. Med. Res., vol. 140, no. 2, pp. 262–270, 2014.
A. Kumar, S. Mukherjee, and R. Chakraborty, "Characterization of a novel trimethoprim resistance gene, dfrA28, in class 1 integron of an oligotrophic Acinetobacter johnsonii strain, MB52, isolated from River Mahananda, India," Microb. Drug Resist., vol. 16, no. 1, pp. 29–37, 2010.
B. Boral et al., "A prospective multicenter study on the evaluation of antimicrobial resistance and molecular epidemiology of multidrug-resistant Acinetobacter baumannii infections in intensive care units with clinical and environmental features," Ann. Clin. Microbiol. Antimicrob., vol. 18, pp. 1–9, 2019.
P. D. Tamma et al., "Infectious Diseases Society of America guidance on the treatment of AmpC beta-lactamase-producing Enterobacterales, Carbapenem-resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia infections," Clin. Infect. Dis., vol. 74, pp. 2089–2114, 2022, doi: 10.1093/cid/ciab1013.
N. Woodford et al., "Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp.," Int. J. Antimicrob. Agents, vol. 27, no. 4, pp. 351–353, 2006.
S. Figueiredo et al., "In vivo selection of reduced susceptibility to carbapenems in Acinetobacter baumannii related to ISAba1-mediated overexpression of the natural blaOXA-66 oxacillinase gene," Antimicrob. Agents Chemother., vol. 6, pp. 2657–2659, 2009.
S. M. Diene and J. M. Rolain, "Investigation of antibiotic resistance in the genomic era of multidrug-resistant Gram-negative bacilli, especially Enterobacteriaceae, Pseudomonas, and Acinetobacter," Expert Rev. Anti Infect. Ther., vol. 11, pp. 277–296, 2013.
J. M. Pogue, T. Mann, K. E. Barber, and K. S. Kaye, "Carbapenem-resistant Acinetobacter baumannii: epidemiology, surveillance, and management," Expert Rev. Anti Infect. Ther., vol. 11, pp. 383–393, 2013.
WHO, "Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics," 2017. [Online]. Available: https://www.who.int/medicines/areas/rational_use/prioritization-of-pathogens/en/. [Accessed: May 01, 2020].
S. Corvec et al., "Genetics and expression of the carbapenem-hydrolyzing oxacillinase gene blaOXA-23 in Acinetobacter baumannii," Antimicrob. Agents Chemother., vol. 51, pp. 1530–1533, 2007.
P. Nowak, P. Paluchowska, and A. Budak, "Co-occurrence of carbapenem and aminoglycoside resistance genes among multidrug-resistant clinical isolates of Acinetobacter baumannii from Cracow, Poland," Med. Sci. Monit. Basic Res., vol. 20, p. 9, 2014.
D. Wong et al., "Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges," Clin. Microbiol. Rev., vol. 30, pp. 409–447, 2017.
H. Wang et al., "Identification of antibiotic resistance genes in the multidrug-resistant Acinetobacter baumannii strain, MDRSHH02, using whole-genome sequencing," Int. J. Mol. Med., vol. 39, pp. 364–372, 2017.
M. S. Ramirez and M. E. Tolmasky, "Aminoglycoside modifying enzymes," Drug Resist. Updat., vol. 13, pp. 151–171, 2010.
Copyright (c) 2024 Maryam Hazem Abduljabbar, Talal Sabhan Salih

This work is licensed under a Creative Commons Attribution 4.0 International License.














