High Carriage of tetA, sul1, sul2 and blaTEM Resistance Genes among the Multidrug-resistant Uropathogenic Escherichia coli (UPEC) Strains from Malaysian Patients
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Abstract
The rapid emergence of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) strains pose a critical challenge in urinary tract infection (UTI) treatments. However, little work elucidated the resistance mechanisms of the MDR UPEC clinical strains in Malaysia. Therefore, this study aimed to determine the antimicrobial susceptibility profiles and the prevalence of antimicrobial resistance genes among the UPEC strains. Polymerase chain reactions were conducted to detect the presence of 6 antimicrobial resistance genes among 60 UPEC strains. Meanwhile, the antimicrobial resistance profiles against 9 antimicrobials were examined through the Kirby-Bauer disk diffusion method. In this study, the MDR isolates accounted for 40.0% (24/60), with the highest prevalence of resistance towards ampicillin (43/60; 71.7%), followed by tetracycline (31/60; 51.7%), nalidixic acid (30/60; 50.0%), co-trimoxazole (20/60, 33.3%), ciprofloxacin (19/60, 31.7%), levofloxacin (16/60, 21.6%) and chloramphenicol (10/60, 16.7%). In contrast, low resistance rates were observed among minocycline (1/60; 1.7%) and imipenem (0/60; 0.0%). blaTEM was the most prevalent gene (36/60; 60.0%), followed by tetA (27/60; 45.0%), sul2 (25/60; 41.7%), sul1 (13/60; 21.7%) and tetB (8/60; 13.3%). Surprisingly, blaSHV was not detected among the UPEC isolates. The MDR, ampicillin and tetracycline-resistant isolates were significantly associated with a higher prevalence of tetA, sul1, sul2 and blaTEM. In contrast, tetB displayed no significant relationship with any of the antimicrobials tested. The patient’s age and gender were not the risk factors for the carriage of the resistance genes. Our findings identified the common resistance genes carried by the antimicrobial resistant UPEC isolates and provide valuable insights into developing the best antibiotic prescription regime to treat UTIs in our local scene.
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References
Abujnah A A, Zorgani A, Sabri M A M, El-Mohammady H, Khalek R A and Ghenghesh K S. (2015). Multidrug resistance and extended-spectrum ?-lactamases genes among Escherichia coli from patients with urinary tract infections in Northwestern Libya. Libyan Journal of Medicine 10(1): 26412. https://doi.org/10.3402/ljm.v10.26412
Adamus-Bia?ek W, Baraniak A, Wawszczak M, G?uszek S, Gad B, Wróbel K, Bator P, Majchrzak M and Parniewski P. (2018). The genetic background of antibiotic resistance among clinical uropathogenic Escherichia coli strains. Molecular Biology Reports 45(5): 1055–1065. https://doi.org/10.1007/s11033-018-4254-0
Alqasim A, Abu J A and Alyousef A A. (2018). Prevalence of multidrug resistance and extended-spectrum ?-lactamase carriage of clinical uropathogenic Escherichia coli isolates in Riyadh, Saudi Arabia. International Journal of Microbiology 2018: 3026851. https://doi.org/10.1155/2018/3026851
Arabi H, Pakzad I, Nasrollahi A, Hosainzadegan H, Azizi J F, Taherikalani M, Samadi N and Monadi S A. (2015). Sulfonamide resistance genes (sul) M in extended spectrum beta lactamase (ESBL) and non-ESBL producing Escherichia coli isolated from Iranian hospitals. Jundishapur Journal of Microbiology 8(7): e19961. https://doi.org/10.5812/jjm.19961v2
Blahna M T, Zalewski C A, Reuer J, Kahlmeter G, Foxman B and Marrs C F. (2006). The role of horizontal gene transfer in the spread of trimethoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli in Europe and Canada. The Journal of Antimicrobial Chemotherapy 57(4): 666–672. https://doi.org/10.1093/jac/dkl020
Bunduki G K, Heinz E, Phiri V S, Noah P, Feasey N and Musaya J. (2021). Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: A systematic review and meta-analysis. BMC Infectious Diseases 21(1): 753. https://doi.org/10.1186/s12879-021-06435-7
Bush K and Bradford P A. (2020). Epidemiology of ?-lactamase-producing pathogens. Clinical Microbiology Reviews 33(2): e00047-19. https://doi.org/10.1128/CMR.00047-19
Castanheira M, Simner P J and Bradford P A. (2021). Extended-spectrum ?-lactamases: An update on their characteristics, epidemiology and detection. JAC-Antimicrobial Resistance 3(3): dlab092. https://doi.org/10.1093/jacamr/dlab092
Chen T, Liu N, Ren P, Xi X, Yang L, Sun W, et al. (2019). Efficient biofilm-based fermentation strategies for L-threonine production by Escherichia coli. Frontiers in Microbiology 10: 1773. https://doi.org/10.3389/fmicb.2019.01773
Chin J J, Choo Q C, Murnihayati H, Ho W Y, Chew C H. (2023). Virulence-associated traits and antimicrobial resistance of the uropathogenic Escherichia coli (UPEC) strains in relation to phylogenetic background and host factors from Malaysian patients. Malaysian Journal of Microbiology 19(2): 211–221. https://doi.org/10.21161/mjm.220134
Chopra I and Roberts M. (2001). Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiology and Molecular Biology Reviews 65(2): 232–260. https://doi.org/10.1128/MMBR.65.2.232–260.2001
Clinical Laboratory Standards Institute (CLSI). (2021). Performance standards for antimicrobial susceptibility testing. https://www.treata.academy/wp-content/uploads/2021/03/CLSI-31-2021.pdf (accessed on 16 November 2022).
Colom K, Perez J, Alonso R, Fernandez-Aranguiz A, Larino E and Cisterna R. (2003). Simple and reliable multiplex PCR assay for detection of blaTEM, blaSHV and blaOXA-1 genes in Enterobacteriaceae. FEMS Microbiology Letters 223(2): 147–151. https://doi.org/10.1016/S0378-1097(03)00306-9
Dormanesh B, Moghny M, Safarpoor D F, Yahaghi E and Khodaverdi D E. (2014). Molecular characterization and antimicrobial resistance of uropathogenic Escherichia coli. Iranian Journal of Biotechnology 12(2): 32–40. https://doi.org/10.5812/IJB.16833
Gundran R S, Cardenio P A, Villanueva M A, Sison F B, Benigno C C, Kreausukon K, Pichpol D and Punyapornwithaya V. (2019). Prevalence and distribution of blaCTX-M, blaSHV, blaTEM genes in extended-spectrum ?-lactamase-producing E. coli isolates from broiler farms in the Philippines. BMC Veterinary Research 15(1): 227. https://doi.org/10.1186/s12917-019-1975-9
Halaji M, Fayyazi A, Rajabnia M, Zare D, Pournajaf A and Ranjbar R. (2022). Phylogenetic group distribution of uropathogenic Escherichia coli and related antimicrobial resistance pattern: A meta-analysis and systematic review. Frontiers in Cellular and Infection Microbiology 12: 790184. https://doi.org/10.3389/fcimb.2022.790184
Haque M, Ara T, Haq M A, Lugova H, Dutta S, Samad N, Rabiu A A, Syed M S S B, Rahman M M, Islam S, Adnan N, Ahmad R, Binti A S L, Ismail M H B and Godman B. (2022). Antimicrobial prescribing confidence and knowledge regarding drug resistance: Perception of medical students in Malaysia and the implications. Antibiotics 11(5): 540. https://doi.org/10.3390/antibiotics11050540
Ibrahim M E, Algak T B, Abbas M and Elamin B K. (2021). Emergence of blaTEM, blaCTX-M, blaSHV and blaOXA genes in multidrug-resistant Enterobacteriaceae and Acinetobacter baumannii in Saudi Arabia. Experimental and Therapeutic Medicine 22(6): 1450. https://doi.org/10.3892/etm.2021.10885
Institute for Medical Research (2020). National antibiotic resistance surveillance report 2020. Kuala Lumpur: Institute for Medical Research. https://www.imr.gov.my/images/uploads/NSAR/2020/NSAR-REPORT-2020.pdf (accessed 21 September 2022).
Jiang X, Liu L, Chen J, Fan X, Xie S, Huang J and Yu G. (2021). Antibiotic resistance genes and mobile genetic elements in a rural river in Southeast China: Occurrence, seasonal variation and association with the antibiotics. The Science of the Total Environment 778: 146131. https://doi.org/10.1016/j.scitotenv.2021.146131
Kor S-B, Choo Q-C and Chew C-H. (2013). New integron gene arrays from multiresistant clinical isolates of members of the Enterobacteriaceae and Pseudomonas aeruginosa from hospitals in Malaysia. Journal of Medical Microbiology 62(Pt 3): 412–420. https://doi.org/10.1099/jmm.0.053645-0
Kot B. (2019). Antibiotic resistance among uropathogenic Escherichia coli. Polish Journal of Microbiology 68(4): 403–415. https://doi.org/10.33073/pjm-2019-048
Lai Y M, Zaw M T, Aung T S, Tin W and Lin Z. (2019). Comparison of the activities among three sul genes present in uropathogenic Escherichia coli. Borneo Journal of Medical Sciences 13(1): 17–22.
Lavigne J P, Bruyère F, Bernard L, Combescure C, Ronco E, Lanotte P, Coloby P, Thibault M, Cariou G, Desplaces N, Costa P and Sotto A. (2016). Resistance and virulence potential of uropathogenic Escherichia coli strains isolated from patients hospitalized in urology departments: A French prospective multicentre study. Journal of Medical Microbiology 65(6): 530–537. https://doi.org/10.1099/jmm.0.000247
Lin W-H, Wang M-C, Liu P-Y, Chen P-S, Wen L-L, Teng C-H and Kao C-Y. (2021). Escherichia coli urinary tract infections: Host age-related differences in bacterial virulence factors and antimicrobial susceptibility. Journal of Microbiology, Immunology, and Infection 55(2): 249–256. https://doi.org/10.1016/j.jmii.2021.04.001
Lin Z, Lai Y M, Zaw M T and Samsudin A T. (2016). Distribution of sul genes and their variants in uropathogenic Escherichia coli isolated from two hospitals of Sabah. Asian Journal of Medical and Biological Research 2(2): 213–220. https://doi.org/10.3329/ajmbr.v2i2.29063
Liu Z, Yao J, Ma H, Rukeya A, Liang Z, Du W and Chen Y. (2022). Bacterial hosts and genetic characteristics of antibiotic resistance genes in wastewater treatment plants of Xinjiang (China) revealed by metagenomics. Applied Sciences 12(6): 3100. https://doi.org/10.3390/app12063100
Mabilat C and Courvalin P. (1990). Development of “oligotyping” for characterization and molecular epidemiology of TEM beta-lactamases in members of the family Enterobacteriaceae. Antimicrobial Agents and Chemotherapy 34(11): 2210–2216. https://doi.org/10.1128/AAC.34.11.2210
Magiorakos A-P, Srinivasan A, Carey R B, Carmeli Y, Falagas M E, Giske C G, Harbarth S, Hindler J F, Kahlmeter G, Olsson-Liljequist B, Paterson D L, Rice L B, Stelling J, Struelens M J, Vatopoulos A, Weber J T and Monnet D L. (2012). Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clinical Microbiology and Infection 18(3): 268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x
Maniam L, Vellasamy K M, Jindal H M, Narayanan V, Danaee M, Vadivelu J and Pallath V. (2022). Demonstrating the utility of Escherichia coli asymptomatic bacteriuria isolates’ virulence profile towards diagnosis and management-a preliminary analysis. PloS One 17(5): e0267296. https://doi.org/10.1371/journal.pone.0267296
Mansouri M and Ramazanzadeh R. (2009). Spread of extended-spectrum beta-lactamase producing Esherichia coli clinical isolates in Sanandaj hospitals. Journal of Biological Sciences 9: 362–366. https://doi.org/10.3923/jbs.2009.362.366
Maynard C, Fairbrother J M, Bekal S, Sanschagrin F, Levesque R C, Brousseau R, Masson L, Larivière S and Harel J. (2003). Antimicrobial resistance genes in enterotoxigenic Escherichia coli O149:K91 isolates obtained over a 23-year period from pigs. Antimicrobial Agents and Chemotherapy 47(10): 3214–3221. https://doi.org/10.1128/aac.47.10.3214-3221.2003
Millanao A R, Mora A Y, Villagra N A, Bucarey S A and Hidalgo A A. (2021). Biological effects of quinolones: A family of broad-spectrum antimicrobial agents. Molecules 26(23): 7153. https://doi.org/10.3390/molecules26237153
Ministry of Health Malaysia (2017). Malaysian action plan on antimicrobial resistance (MyAP-AMR) 2017–2021. https://www.moh.gov.my/moh/resources/Penerbitan/Garis%20Panduan/Garis%20panduan%20Umum%20(Awam)/National_Action_Plan_-_FINAL_29_june.pdf (accessed on 16 November 2022).
Mortazavi-Tabatabaei S A R, Ghaderkhani J, Nazari A, Sayehmiri K, Sayehmiri F and Pakzad I. (2019). Pattern of antibacterial resistance in urinary tract infections: A systematic review and meta-analysis. International Journal of Preventive Medicine 10: 169. https://doi.org/10.4103/ijpvm.IJPVM_419_17
Munkhdelger Y, Gunregjav N, Dorjpurev A, Juniichiro N and Sarantuya J. (2017). Detection of virulence genes, phylogenetic group and antibiotic resistance of uropathogenic Escherichia coli in Mongolia. The Journal of Infection in Developing Countries 11(1): 51–57. https://doi.org/10.3855/jidc.7903
Naeemmudeen N M, Mohd G, N A N, Bahari H, Ibrahim R, Samsudin A D and Jasni A S. (2021). Trends in antimicrobial resistance in Malaysia. The Medical Journal of Malaysia 76(5): 698–705.
Olowe O A, Idris O J and Taiwo S S. (2013). Prevalence of tet genes mediating tetracycline resistance in Escherichia coli clinical isolates in Osun State, Nigeria. European Journal of Microbiology and Immunology 3(2): 135–140. https://doi.org/10.1556/EuJMI.3.2013.2.7
Poirel L, Madec J-Y, Lupo A, Schink A-K, Kieffer N, Nordmann P and Schwarz S. (2018). Antimicrobial resistance in Escherichia coli. Microbiology Spectrum 6(4): 1–27. https://doi.org/10.1128/microbiolspec.ARBA-0026-2017
Ramírez-Castillo F Y, Moreno-Flores A C, Avelar-González F J, Márquez-Díaz F, Harel J and Guerrero-Barrera A L. (2018). An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: Cross-sectional study. Annals of Clinical Microbiology and Antimicrobials 17(1): 34. https://doi.org/10.1186/s12941-018-0286-5
Rozwadowski M and Gawel D. (2022). Molecular factors and mechanisms driving multidrug resistance in uropathogenic Escherichia coli: An update. Genes 13(8): 1397. https://doi.org/10.3390/genes13081397
Salah F D, Soubeiga S T, Ouattara A K, Sadji A Y, Metuor-Dabire A, Obiri-Yeboah D, Banla-Kere A, Karou S and Simpore J. (2019). Distribution of quinolone resistance gene (qnr) in ESBL-producing Escherichia coli and Klebsiella spp. in Lomé, Togo. Antimicrobial Resistance and Infection Control 8: 104. https://doi.org/10.1186/s13756-019-0552-0
Shinu P, Bareja R, Nair A B, Mishra V, Hussain S, Venugopala K N, Sreeharsha N, Attimarad M and Rasool S T. (2020). Monitoring of non-?-lactam antibiotic resistanceassociated genes in ESBL producing Enterobacterales isolates. Antibiotics 9(12): 884. https://doi.org/10.3390/antibiotics9120884
Suaifan G A R Y, Mohammed A A M and Alkhawaja B A. (2022). Fluoroquinolones’ biological activities against laboratory microbes and cancer cell lines. Molecules 27(5): 1658. https://doi.org/10.3390/molecules27051658
Tewawong N, Kowaboot S, Pimainog Y, Watanagul N, Thongmee T and Poovorawan Y. (2020). Distribution of phylogenetic groups, adhesin genes, biofilm formation, and antimicrobial resistance of uropathogenic Escherichia coli isolated from hospitalized patients in Thailand. PeerJ 8: e10453. https://doi.org/10.7717/peerj.10453
Valadbeigi H, HatamiLak M, Maleki A, Kouhsari E and Sadeghifard N. (2020). Molecular characteristics, antimicrobial resistance profiles, and antibiotic resistance determinants in uropathogenic fluoroquinolone resistant-Escherichia coli isolates. Gene Reports 18: 100584. https://doi.org/10.1016/j.genrep.2019.100584
Xiao L, Wang X, Kong N, Zhang L, Cao M, Sun M, Wei Q and Liu W. (2019). Characterization of beta-lactamases in bloodstream-infection Escherichia coli: Dissemination of blaADC–162 and blaCMY–2 among bacteria via an IncF plasmid. Frontiers in Microbiology 10: 2175. https://doi.org/10.3389/fmicb.2019.02175
Xu F, Min F, Wang J, Luo Y, Huang S, Chen M, Wu R and Zhang Y. (2020). Development and evaluation of a Luminex xTAG assay for sulfonamide resistance genes in Escherichia coli and Salmonella isolates. Molecular and Cellular Probes 49: 101476. https://doi.org/10.1016/j.mcp.2019.101476
Yang W, Liu P, Chen Y, Lv Q, Wang Z, Huang W, Jiang H, Zheng Y, Jiang Y and Sun L. (2022). Dictamnine inhibits the adhesion to and invasion of uropathogenic Escherichia coli (UPEC) to urothelial cells. Molecules 27(1): 272. https://doi.org/10.3390/molecules27010272
Y?lmaz E ? and Aslanta? Ö. (2020). Phylogenetic group/subgroups distributions, virulence factors, and antimicrobial susceptibility of Escherichia coli strains from urinary tract infections in Hatay. Revista da Sociedade Brasileira de Medicina Tropical 53: e20190429. https://doi.org/10.1590/0037-8682-0429-2019
Zeadan A M, Saleem A J and Abbas S M. (2022). Detection and analysis of resistance genes in Escherichia coli bacteria isolated from children in Baghdad. Advanced Gut and Microbiome Research 2022: 1–7. https://doi.org/10.1155/2022/1450019
Zhu Y, Huang W E and Yang Q. (2022). Clinical perspective of antimicrobial resistance in bacteria. Infection and Drug Resistance 15: 735–746. https://doi.org/10.2147/IDR.S345574