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. 2019 Apr 8;19(1):76.
doi: 10.1186/s12866-019-1439-1.

gyrA and parC mutations in fluoroquinolone-resistant Neisseria gonorrhoeae isolates from Kenya

Mary Wandia Kivata  1   2 , Margaret Mbuchi  3   4 , Fredrick Lunyagi Eyase  3   5 , Wallace Dimbuson Bulimo  3   6 , Cecilia Katunge Kyanya  3 , Valerie Oundo  3 , Simon Wachira Muriithi  3 , Ben Andagalu  3 , Wilton Mwema Mbinda  7 , Olusegun O Soge  8 , R Scott McClelland  8 , Willy Sang  3   4 , James D Mancuso  3
Affiliations

gyrA and parC mutations in fluoroquinolone-resistant Neisseria gonorrhoeae isolates from Kenya

Mary Wandia Kivata et al. BMC Microbiol. .

Abstract

Background: Phenotypic fluoroquinolone resistance was first reported in Western Kenya in 2009 and later in Coastal Kenya and Nairobi. Until recently gonococcal fluoroquinolone resistance mechanisms in Kenya had not been elucidated. The aim of this paper is to analyze mutations in both gyrA and parC responsible for elevated fluoroquinolone Minimum Inhibitory Concentrations (MICs) in Neisseria gonorrhoeae (GC) isolated from heterosexual individuals from different locations in Kenya between 2013 and 2017.

Methods: Antimicrobial Susceptibility Tests were done on 84 GC in an ongoing Sexually Transmitted Infections (STI) surveillance program. Of the 84 isolates, 22 resistant to two or more classes of antimicrobials were chosen for analysis. Antimicrobial susceptibility tests were done using E-test (BioMerieux) and the results were interpreted with reference to European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. The isolates were sub-cultured, and whole genomes were sequenced using Illumina platform. Reads were assembled de novo using Velvet, and mutations in the GC Quinolone Resistant Determining Regions identified using Bioedit sequence alignment editor. Single Nucleotide Polymorphism based phylogeny was inferred using RaxML.

Results: Double GyrA amino acid substitutions; S91F and D95G/D95A were identified in 20 isolates. Of these 20 isolates, 14 had an additional E91G ParC substitution and significantly higher ciprofloxacin MICs (p = 0.0044*). On the contrary, norfloxacin MICs of isolates expressing both GyrA and ParC QRDR amino acid changes were not significantly high (p = 0.82) compared to MICs of isolates expressing GyrA substitutions alone. No single GyrA substitution was found in the analyzed isolates, and no isolate contained a ParC substitution without the simultaneous presence of double GyrA substitutions. Maximum likelihood tree clustered the 22 isolates into 6 distinct clades.

Conclusion: Simultaneous presence of amino acid substitutions in ParC and GyrA has been reported to increase gonococcal fluoroquinolone resistance from different regions in the world. Our findings indicate that GyrA S91F, D95G/D95A and ParC E91G amino acid substitutions mediate high fluoroquinolone resistance in the analyzed Kenyan GC.

Keywords: Antimicrobial resistance (AMR); Fluoroquinolones; Mutation; Neisseria gonorrhoeae; Quinolone resistant determining regions (QRDR).

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Conflict of interest statement

Ethics approval and consent to participate

Permission to carry out the study was obtained from both Kenya Medical Research Institute Scientific and Ethics Review Unit (SERU) and Walter Reed Army Institute of Research (WRAIR) Human Subject Protection Board (HSPB) (KEMRI/SERU/CCR/0053/3385: WRAIR#1743A). Consent to participate is not applicable for this study because it was retrospective laboratory based, used archived samples, and there was no interaction with subjects.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Maximum likelihood SNP phylogenetic tree inferred using RaxML. The 22 study isolates (KNY) in red and 4 Kenyan isolates (in green) downloaded from NCBI (64500, 66098, 50659, and 42876) and previously obtained from MSM population clustered closely together into six distinct clades shown in red circles
Fig. 2
Fig. 2
Ciprofloxacin (a) and Norfloxacin (b) MICs of GC isolates expressing QRDR amino acid substitutions. The central bars across each group of points locates the median for that group
See this image and copyright information in PMC

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