Investigation of biocide resistance genes in Acinetobacter baumannii isolates

Yıl 2023, Cilt: 16 Sayı: 2, 191 - 199, 17.08.2023

Harun Gülbudak , Gizem Görgülü , Efdal Oktay Gultekin , Seda Tezcan Ülger , Nuran Delialioğlu , Gönül Aslan

Öz

Objective: Acinetobacter species are opportunistic pathogens that often cause nosocomial infections. Antiseptics and disinfectants play an important role in the prevention of healthcare-associated infections. However, the widespread use of biocides in hospitals may cause emergence of resistance in bacteria. In this study, it was aimed to investigate the frequency of qacE, qacE∆1 and cepA genes associated with biocide resistance in A. baumannii strains. Method: In this study, 51 A. baumannii strains isolated from clinical specimens were included. Identification and antibiotic susceptibility tests were performed with Microscan automated system. A. baumannii strains were confirmed by presence of the blaOxa-51-like gene. Biocide resistance genes qacE, qacE∆1 and cepA were investigated by PCR method. Results: In the study, qacE and qacE∆1 genes were detected in 51.0%(n=26) and 47.1% (n=24), respectively. However, cepA gene was found negative in all isolates. Multi-drug resistance (MDR) was detected in 84.3% (n=43) of the isolates. qacE and qacE∆1 genes were found positive 41.9% (n=18), and 44.2% (n=19) in MDR isolates, while 100% (n=8) and 62.5% (n=5) were found positive in susceptible isolates. While there was no statistical difference in qacEΔ1 positivity between MDR and susceptible isolates (p=0.341); qacE positivity was found at a lower rate in MDR isolates than in susceptible ones (p<0.05). Conclusion: As a result, qacE and qacE∆1 biocide resistance genes were found high in MDR and susceptible A. baumannii isolates. Therefore, it is important to consider that susceptible isolates may also be resistant to biocides in the prevention and control of nosocomial A. baumannii infections in hospitals.

Anahtar Kelimeler

: A. baumannii, qacE, qacEΔ1, cepA, biocides

Acinetobacter baumannii izolatlarında biyosit direnç genlerinin araştırılması

Öz

Amaç: Acinetobacter türleri sıklıkla yoğun bakım ünitesinde yatan hastalarda nozokomiyal enfeksiyonlara neden olan fırsatçı patojenlerdir. Hastane enfeksiyonlarının önlenmesinde antiseptikler ve dezenfektanlar önemli rol oynamaktadır. Ancak biyositlerin yaygın olarak kullanılması bakterilerin dirençli hale gelmesine neden olmaktadır. Bu çalışmada klinik örneklerden izole edilen A. baumannii suşlarında biyosit direnci ile ilişkili qacE, qacE∆1 ve cepA gen bölgeleri sıklığının araştırılması amaçlanmıştır. Yöntem: Çalışmaya, klinik örneklerden izole edilen, 51 A. baumannii izolatı dahil edildi. Microscan otomatize sistemi ile identifikasyon ve antibiyotik duyarlılık testleri yapıldı. A. baumannii türleri blaOxa-51-like gen varlığı ile doğrulandı. Biyosit direnç gen bölgeleri qacE, qacE∆1 ve cepA PCR yöntemi ile araştırıldı. Bulgular: Çalışmada, qacE ve qacE∆1 genleri sırasıyla %51.0 (n=26) ve %47.1 (n=24) oranında tespit edilmiştir. Ancak cepA geni izolatların tamamında negatif bulunmuştur. İzolatların %84.3 (n=43)’ünde çoklu ilaç direnci (ÇİD) tespit edilmiştir. ÇİD izolatlarda qacE %41.9(n=18), qacE∆1 %44.2 (n=19) oranında pozitif; duyarlı izolatlarda ise qacE %100(n=8) ve qacE∆1 %62.5(n=5) oranında pozitif bulunmuştur. ÇİD ve duyarlı izolatlar arasında qacEΔ1 pozitifliğinde istatistiksel bir fark saptanmazken (p=0.341); ÇİD izolatlarda qacE pozitifliği duyarlı olanlara göre daha düşük oranda bulunmuştur (p<0.05). Sonuç: Sonuç olarak bu çalışmada, ÇİD ve duyarlı A. baumannii izolatlarında qacE ve qacE∆1 biyosit direnç genleri yüksek oranda bulunmuştur. Bu yüzden hastanelerde nozokomiyal A. baumannii enfeksiyonlarının önlenmesinde ve kontrolünde duyarlı izolatların da biyositlere dirençli olabileceğinin dikkate alınması önemlidir.

Anahtar Kelimeler

A. baumannii, qacE, qacEΔ1, cepA, biyosit

Kaynakça

• Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol. 2007; 5(12):939-951. doi: 10.1038/nrmicro1789.
• Vijayakumar S, Biswas I, Veeraraghavan B. Accurate identification of clinically important Acinetobacter spp.: an update. Future Sci OA. 2019;5(6):FSO395. doi: 10.2144/fsoa-2018-0127.
• Gulbudak H, Aslan G, Tezcan S, et al. Investigation of the clonal relationship between nosocomial Acinetobacter baumannii isolates by rep-PCR. Mikrobiyol Bul. 2014;48(2):316-24. doi: 10.5578/mb.7225.
• Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: Emergence of a successful pathogen. Clin Microbiol Rev. 2008; 21(3): 538-582. doi: 10.1128/CMR.00058-07.
• Shan W, Kan J, Cai X, Yin M. Insights into mucoid Acinetobacter baumannii: A review of microbiological characteristics, virulence, and pathogenic mechanisms in a threatening nosocomial pathogen. Microbiol Res. 2022; 261:127057. doi: 10.1016/j.micres.2022.127057.
• Milstone AM, Passaretti CL, Perl TM. Chlorhexidine: expanding the armamentarium for infection control and prevention. Clin Infect Dis. 2008;46(2):274-81. doi: 10.1086/524736.
• Jennings MC, Minbiole KP, Wuest WM. Quaternary ammonium compounds: An antimicrobial mainstay and platform for ınnovation to address bacterial resistance. ACS Infect Dis. 2015;1(7):288-303. doi: 10.1021/acsinfecdis.5b00047
• Russell AD. Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations. Lancet Infect Dis. 2003;3(12):794-803. doi: 10.1016/s1473-3099(03)00833-8.
• Jaglic Z, Cervinkova D. Genetic basis of resistance to quaternary ammonium compounds – the qac genes and their role: a review. Veterinarni Medicina. 2012;57(6): 275–281. doi: 10.17221/6013-VETMED.
• Kosyakova KG, Esaulenko NB, Kameneva OA et al. Prevalence of carbapenemase genes, qacE, qacEΔ1 and cepA in multidrug-resistant Gram-negative bacteria with different susceptibility to chlorhexidine. Epidemiology and Vaccinal Prevention. 2020;19(5):49–60. doi: 10.31631/2073-3046-2020-19-5-49-60
• Fang CT, Chen HC, Chuang YP, Chang SC, Wang JT. Cloning of a cation efflux pump gene associated with chlorhexidine resistance in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2002;46(6):2024-8. doi: 10.1128/AAC.46.6.2024-2028.2002.
• Vijayakumar R, Sandle T, Al-Aboody MS, et al. Distribution of biocide resistant genes and biocides susceptibility in multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii - A first report from the Kingdom of Saudi Arabia. J Infect Public Health. 2018;11(6):812-816. doi: 10.1016/j.jiph.2018.05.011.
• Sajduda A, Brzostek A, Poplawska M, et al. Molecular characterization of rifampin- and isoniazid-resistant Mycobacterium tuberculosis strains isolated in Poland. J Clin Microbiol, 2004;42(6):2425-31. doi: 10.1128/JCM.42.6.2425-2431.2004.
• Turton JF, Woodford N, Glover J, Yarde S, Kaufmann ME, Pitt TL. Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemasegene intrinsic to this species. J Clin Microbiol. 2006;44(8):2974-6. doi: 10.1128/JCM.01021-06.
• Babaei M, Sulong A, Hamat R, Nordin S, Neela V. Extremely high prevalence of antiseptic resistant quaternary ammonium compound E gene among clinical isolates of multiple drug resistant Acinetobacter baumannii in Malaysia. Ann Clin Microbiol Antimicrob. 2015;14:11. doi: 10.1186/s12941-015-0071-7.
• Wang C, Cai P, Guo Y, Mi Z. Distribution of the antiseptic-resistance genes qacEDelta1 in 331 clinical isolates of Pseudomonas aeruginosa in China. J Hosp Infect. 2007;66(1):93-5. doi: 10.1016/j.jhin.2007.01.012.
• Chaoui L, Mhand R, Mellouki F, Rhallabi N. Contamination of the surfaces of a health care environment by multidrug-resistant (MDR) bacteria. Int J Microbiol. 2019;2019:3236526. doi: 10.1155/2019/3236526.
• Fuangthong M, Julotok M, Chintana W, et al. Exposure of Acinetobacter baylyi ADP1 to the biocide chlorhexidine leads to acquired resistance to the biocide itself and to oxidants. Journal of Antimicrobial Chemotherapy. 2011;66(2):319-22. doi: 10.1093/jac/dkq435.
• Apisarnthanarak A, Yang Hsu L, Lim TP, Mundy LM. Increase in chlorhexidine minimal inhibitory concentration of Acinetobacter baumannii clinical isolates after implementation of advanced source control. Infect Control Hosp Epidemiol. 2014;35(1):98-9. doi: 10.1086/674404.
• Paulsen IT, Littlejohn TG, Rådström P, et al. The 3' conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants. Antimicrob Agents Chemother. 1993;37(4):761-8. doi: 10.1128/AAC.37.4.761.
• Nor A'shimi MH, Alattraqchi AG, Mohd Rani F, et al. Biocide susceptibilities and biofilm-forming capacities of Acinetobacter baumannii clinical isolates from Malaysia. J Infect Dev Ctries. 2019;13(7):626-633. doi: 10.3855/jidc.11455.
• Guo J, Li C. Molecular epidemiology and decreased susceptibility to disinfectants in carbapenem-resistant Acinetobacter baumannii isolated from intensive care unit patients in central China. J Infect Public Health. 2019;12(6):890-896. doi: 10.1016/j.jiph.2019.06.007.
• Lin F, Xu Y, Chang Y, Liu C, Jia X, Ling B. Molecular characterization of reduced susceptibility to biocides in clinical isolates of Acinetobacter baumannii. Front Microbiol. 2017;8:1836. doi: 10.3389/fmicb.2017.01836.
• Elkhatib WF, Khalil MAF, Ashour HM. Integrons and antiseptic resistance genes mediate resistance of Acinetobacter baumannii and Pseudomonas aeruginosa isolates from intensive care unit patients with wound infections. Curr Mol Med. 2019;19(4):286-293. doi: 10.2174/1566524019666190321113008.
• Shirmohammadlou N, Zeighami H, Haghi F, Kashefieh M. Resistance pattern and distribution of carbapenemase and antiseptic resistance genes among multidrug-resistant Acinetobacter baumannii isolated from intensive care unit patients. J Med Microbiol. 2018;67(10):1467-1473. doi: 10.1099/jmm.0.000826.
• Khosravi AD, Montazeri EA, Maki SR. Antibacterial effects of Octenicept, and benzalkonium chloride on Acinetobacter baumannii strains isolated from clinical samples and determination of genetic diversity of isolates by RAPD-PCR method. Mol Biol Rep. 2021;48(11):7423-7431. doi: 10.1007/s11033-021-06758-3.
• Gomaa FAM, Helal ZH, Khan MI. High Prevalence of blaNDM-1, blaVIM, qacE, and qacEΔ1 Genes and their association with decreased susceptibility to antibiotics and common hospital biocides in clinical ısolates of Acinetobacter baumannii. Microorganisms. 2017;5(2):18. doi: 10.3390/microorganisms5020018.
• Kücken D, Feucht HH, Kaulfers PM. Association of qacE and qacEΔ1 with multiple resistance to antibiotics and antiseptics in clinical isolates of Gram-negative bacteria. FEMS Microbiol Lett. 2000;183(1):95–98. doi: 10.1111/j.1574-6968.2000.tb08939.x.
• Kõljalg S, Naaber P, Mikelsaar M. Antibiotic resistance as an indicator of bacterial chlorhexidine susceptibility. J Hosp Infect. 2002;51(2):106-13. doi: 10.1053/jhin.2002.1204.
• Capita R, Riesco-Peláez F, Alonso-Hernando A, Alonso-Calleja C. Exposure of Escherichia coli ATCC 12806 to sublethal concentrations of food-grade biocides influences its ability to form biofilm, resistance to antimicrobials, and ultrastructure. Appl Environ Microbiol. 2014;80(4):1268-80. doi: 10.1128/AEM.02283-13.
• Webster J, Faoagali JL, Cartwright D. Elimination of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit after hand washing with triclosan. J Paediatr Child Health. 1994;30(1):59-64. doi: 10.1111/j.1440-1754.1994.tb00568.x.
• Betchen M, Giovinco HM, Curry M, et al. Evaluating the effectiveness of hospital antiseptics on multidrug-resistant Acinetobacter baumannii: understanding the relationship between microbicide and antibiotic resistance. Antibiotics (Basel). 2022;11(5):614. doi: 10.3390/antibiotics11050614.
• Romão C, Miranda CA, Silva J, Mandetta Clementino M, de Filippis I, Asensi M. Presence of qacEΔ1 gene and susceptibility to a hospital biocide in clinical isolates of Pseudomonas aeruginosa resistant to antibiotics. Curr Microbiol. 2011;63(1):16-21. doi: 10.1007/s00284-011-9934-0.