Identification of two novel type II topoisomerase mutations in Enterococcus spp. isolated from a hospital in China
DOI:
https://doi.org/10.2298/ABS210628034SKeywords:
Enterococcus spp, Type II topoisomerase, GyrA, ParC, Fluoroquinolone resistanceAbstract
Paper description:
- The mutational status of type II topoisomerases and the relationship of mutations with quinolone resistance is incompletely understood.
- DNA sequencing was performed to investigate the mutational status of the quinolone resistance-determining regions of type II topoisomerases in clinical isolates of enterococci.
- Two novel substitutions of faecalis were identified. Three-dimensional modeling revealed that these novel amino acid substitutions disrupt the water/metal-ion bridge and decrease the interaction between enzymes and ciprofloxacin.
- These results elucidate the mechanisms of type II topoisomerase-mediated quinolone resistance in clinical isolates of enterococci.
Abstract: Type II topoisomerases, including DNA gyrase (GyrA) and topoisomerase IV (ParC), contribute to fluoroquinolone resistance in Enterococcus spp. This study investigated the mutational status of the quinolone resistance-determining regions (QRDRs) of GyrA and ParC in the clinical isolates of enterococci from a hospital in Baotou, China. We analyzed 110 enterococcal isolates, including 57 Enterococcus faecalis and 53 Enterococcus faecalis faecium. The resistance rates of E. faecalis and E. faecium to ciprofloxacin were 63.16% and 84.91%, respectively. We found that 32 samples of E. faecalis and 42 of E. faecium had single or combined mutations in gyrA and/or parC, which were all resistant to ciprofloxacin. Only two ciprofloxacin-resistant E. faecalis isolates had no mutation. No mutations in gyrA and parC genes in all ciprofloxacin-susceptible isolates were found. Ciprofloxacin minimal inhibitory concentrations (MICs) in the mutation group were significantly higher than those of the non-mutation group, indicating that mutations in the QRDRs of gyrA and parC were correlated with MIC elevation. Two novel substitutions (GyrA Ser83Phe and ParC Ser80Leu) of E. faecalis were identified herein. Three-dimensional modeling revealed that these novel amino acid substitutions could disrupt the water/metal-ion bridge and decrease the interaction between the enzymes and ciprofloxacin. The data showed a diversity of mutation types in QRDRs of type II topoisomerases whose association with fluoroquinolone resistance in clinical isolates of enterococci warrants further investigation.
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Tian Y, Yu H, Wang Z. Distribution of acquired antibiotic resistance genes among Enterococcus spp. isolated from a hospital in Baotou, China. BMC Res Notes. 2019;12(1):27. https://doi.org/10.1186/s13104-019-4064-z
Fiore E, Van Tyne D, Gilmore MS. Pathogenicity of enterococci. Microbiol Spectr. 2019;7(4):GPP3-0053-2018. https://doi.org/10.1128/microbiolspec.GPP3-0053-2018
Kim JK, Nam KY, Chung IY, Jeung WJ, Kwon YH, Park JM, Han YS, Lee JE, Byon IS, Park SH, Kim HW, Park KY, Yoon HS, Park I, Kim HW, Lee SJ. Emerging Enterococcus isolates in postoperative endophthalmitis by selection pressure of fluoroquinolones: an 11-year multicenter and experimental study. Emerg Microbes Infect. 2020;9(1):1892-9. https://doi.org/10.1080/22221751.2020.1810134
Zhang Y, Du M, Chang Y, Chen LA, Zhang Q. Incidence, clinical characteristics, and outcomes of nosocomial Enterococcus spp. bloodstream infections in a tertiary-care hospital in Beijing, China: a four-year retrospective study. Antimicrob Resist Infect Control. 2017;6:73. https://doi.org/10.1186/s13756-017-0231-y
Zhou C, Niu H, Yu H, Zhou L, Wang Z. Effects of two novel amino acid substitutions on the penicillin binding properties of the PBP5 C terminal from Enterococcus faecium. Mol Med Rep. 2015;12(4):5281-5. https://doi.org/10.3892/mmr.2015.4057
Asadollahi P, Razavi S, Asadollahi K, Pourshafie MR, Talebi M. Rise of antibiotic resistance in clinical enterococcal isolates during 2001-2016 in Iran: a review. New Microbes New Infect. 2018;26:92-9. https://doi.org/10.1016/j.nmni.2018.08.018
Schaberg DR, Dillon WI, Terpenning MS, Robinson KA, Bradley SF, Kauffman CA. Increasing resistance of enterococci to ciprofloxacin. Antimicrob Agents Chemother. 1992;36(11):2533-5. https://doi.org/10.1128/AAC.36.11.2533
Tankovic J, Mahjoubi F, Courvalin P, Duval J, Leclerco R. Development of fluoroquinolone resistance in Enterococcus faecalis and role of mutations in the DNA gyrase gyrA gene. Antimicrob Agents Chemothe. 1996;40(11):2558-61. https://doi.org/10.1128/AAC.40.11.2558
Schulz J, Kemper N, Hartung J, Janusch F, Mohring SAI, Hamscher G. Analysis of fluoroquinolones in dusts from intensive livestock farming and the co-occurrence of fluoroquinolone-resistant Escherichia coli. Sci Rep. 2019;9(1):5117. https://doi.org/10.1038/s41598-019-41528-z
Talukder KA, Khajanchi BK, Islam MA, Islam Z, Dutta DK, Rahman M, Watanabe H, Nair GB, Sack DA. Fluoroquinolone resistance linked to both gyrA and parC mutations in the quinolone resistance-determining region of Shigella dysenteriae type 1. Curr Microbiol. 2006;52(2):108-11. https://doi.org/10.1007/s00284-005-0140-9
Naeem A, Badshah SL, Muska M, Ahmad N, Khan K. The current case of quinolones: synthetic approaches and antibacterial activity. Molecules. 2016;21(4):268. https://doi.org/10.3390/molecules21040268
Aldred KJ, Schwanz HA, Li G, Williamson BH, McPherson SA, Turnbough CL Jr, Kerns RJ, Osheroff N. Activity of quinolone CP-115,955 against bacterial and human type II topoisomerases is mediated by different interactions. Biochemistry. 2015;54(5):1278-86. https://doi.org/10.1021/bi501073v
Hooper DC. Fluoroquinolone resistance among Gram-positive cocci. Lancet Infect Dis. 2002;2(9):530-8. https://doi.org/10.1016/S1473-3099(02)00369-9
Piekarska K, Gierczyński R, Ławrynowicz-Paciorek M, Kochman M, Jagielski M. Novel gyrase mutations and characterization of ciprofloxacin-resistant clinical strains of Enterococcus faecalis isolated in Poland. Pol J Microbiol. 2008;57(2):121-4.
Macovei L, Zurek L. Ecology of antibiotic resistance genes: characterization of enterococci from house flies collected in food settings. Appl Environ Microbiol. 2006;72(6):4028-35. https://doi.org/10.1128/AEM.00034-06
Patel JB, Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 26th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2016. 252 p. (Clinical and Laboratory Standards Institute (Series); Vol. 36; No. 1).
Kanematsu E, Deguchi T, Yasuda M, Kawamura T, Nishino Y, Kawada Y. Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV associated with quinolone resistance in Enterococcus faecalis. Antimicrob Agents Chemother. 1998;42(2):433-5. https://doi.org/10.1128/AAC.42.2.433
Webb B, Sali A. Protein structure modeling with MODELLER. Methods Mol Biol. 2017;1654:39-54. https://doi.org/10.1007/978-1-4939-7231-9_4
Kolaskar AS, Sawant S. Prediction of conformational states of amino acids using a Ramachandran plot. Int J Pept Protein Res. 1996;47(1-2):110-6. https://doi.org/10.1111/j.1399-3011.1996.tb00817.x
Li X, Yang M, Ke Y, Liu M, Wang Y, Liu S, Liu B, Chen Z. Hfq mutation confers increased cephalosporin resistance in Klebsiella pneumoniae. Arch Biol Sci. 2017;69(1):61-9. https://doi.org/10.2298/ABS160126078L
Berić T, Biočanin M, Stanković S, Dimkić I, Janakiev T, Fira Đorđe, Lozo J. Identification and antibiotic resistance of Bacillus spp. isolates from natural samples. Arch Biol Sci. 2018;70(3):581-8. https://doi.org/10.2298/ABS180302019B
Ferede ZT, Tullu KD, Derese SG, Yeshanew AG. Prevalence and antimicrobial susceptibility pattern of Enterococcus species isolated from different clinical samples at Black Lion Specialized Teaching Hospital, Addis Ababa, Ethiopia. BMC Res Notes. 2018;11(1):793. https://doi.org/10.1186/s13104-018-3898-0
Kim MC, Woo GJ. Characterization of antimicrobial resistance and quinolone resistance factors in high-level ciprofloxacin-resistant Enterococcus faecalis and Enterococcus faecium isolates obtained from fresh produce and fecal samples of patients. J Sci Food Agric. 2017;97(9):2858-64. https://doi.org/10.1002/jsfa.8115
Say Coskun US. Investigation of the relationship between virulence factors and antibiotic resistance of Enterococci isolates. Cell Mol Biol (Noisy-le-grand). 2019;65(2):14-7. https://doi.org/10.14715/cmb/2019.65.2.3
Fàbrega A, Madurga S, Giralt E, Vila J. Mechanism of action of and resistance to quinolones. Microb Biotechnol. 2009;2(1):40-61. https://doi.org/10.1111/j.1751-7915.2008.00063.x
Hooper DC, Jacoby GA. Topoisomerase inhibitors: fluoroquinolone mechanisms of action and resistance. Cold Spring Harb Perspect Med. 2016;6(9):a025320. https://doi.org/10.1101/cshperspect.a025320
Goñi-Urriza M, Arpin C, Capdepuy M, Dubois V, Caumette P, Quentin C. Type II topoisomerase quinolone resistance-determining regions of Aeromonas caviae, A. hydrophila, and A. sobria complexes and mutations associated with quinolone resistance. Antimicrob Agents Chemother. 2002;46(2):350-9. https://doi.org/10.1128/AAC.46.2.350-359.2002
Farahi RM, Ali AA, Gharavi S. Characterization of gyrA and parC mutations in ciprofloxacin-resistant Pseudomonas aeruginosa isolates from Tehran hospitals in Iran. Iran J Microbiol. 2018;10(4):242-9.
Lentz SRC, Chheda PR, Oppegard LM, Towle TR, Kerns RJ, Hiasa H. The C7-aminomethylpyrrolidine group rescues the activity of a thio-fluoroquinolone. Biochimie. 2019;160:24-7. https://doi.org/10.1016/j.biochi.2019.02.002
Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry. 2014;53(10):1565-74. https://doi.org/10.1021/bi5000564
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