Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in non-tuberculous mycobacteria isolates from Kenya

Zakayo Mwangi; Grace Naeku; Marianne Mureithi; Frank Onyambu; Wallace Bulimo

doi:10.12688/f1000research.124002.5

Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in non-tuberculous mycobacteria isolates from Kenya

F1000Res. 2023 Apr 3:11:962. doi: 10.12688/f1000research.124002.5. eCollection 2022.

Authors

Zakayo Mwangi^{1

2}, Grace Naeku³, Marianne Mureithi¹, Frank Onyambu^{2

4}, Wallace Bulimo⁵

Affiliations

¹ Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Nairobi, 30197, Kenya.
² Department of Medical Laboratory Science, Meru University of Science and Technology, Meru, Meru, 972, Kenya.
³ Molecular and Infectious Disease Research Laboratory, University of Nairobi, Nairobi, Nairobi, 30197, Kenya.
⁴ Centre for Molecular Biosciences and Genomics, Centre for Molecular Biosciences and Genomics, Nairobi, Nairobi, 29408, Kenya.
⁵ Kenya Medical Research Institute, Kenya Medical Research Institute, Nairobi, Nairobi, 54840, Kenya.

Abstract

Background: Non-tuberculous mycobacteria (NTM) treatment constitutes a macrolide-based antibiotic regimen in combination with aminoglycosides for Rapid-Growing Mycobacteria (RGM), and rifampicin for Slow-Growing Mycobacteria (SGM). Mutations in the anti-NTM drug target regions promote NTM evolution to mutant strains that are insusceptible to NTM drugs leading to treatment failure. We, therefore, described the mutation patterns of anti-NTM drug target genes including rrl, rrs, and rpoB in NTM isolates from Kenya. Methods: We carried out a cross-sectional study that included 122 NTM obtained from the sputum of symptomatic tuberculosis-negative patients in Kenya. All 122 NTM underwent targeted sequencing of the rrl gene. The 54 RGM were also sequenced for rrs, and the 68 SGM were sequenced for rpoB genes using ABI 3730XL analyzer. The obtained sequences were aligned to their wild-type reference sequences for each gene using Geneious then mutations were identified. Pearson chi-square at a 95% confidence interval tested the association of NTM to mutation patterns for each gene.

Results: NTM harboring mutations associated with resistance to at least one of the antibiotics used in the macrolide-based therapy were 23% (28/122). Of these NTM, 10.4% (12/122) had mutations in the rrl gene with 58.3% (7/12) comprising RGM and 41.7% (5/12) being SGM. Mutation at position 2058 (A2058G, A2058C, A2058T) of the rrl gene was seen for 83.3% (10/12) of NTM, while 16.6% (2/12) harbored a A2059G mutation. Of the 54 RGM included for rrs characterization, 11.1% (6/54) exhibited mutations at position 1408(A1408G), while 14.7% (10/68) of the SGM had mutations in the rpoB gene at positions S531W, S531L, S531Y, F506L, E509H with M.gastri having multiple mutations at positions D516V, H526D and, S531F.

Conclusion: We demonstrated a significant level of mutations associated with drug resistance for macrolides, aminoglycosides, and rifampicin in NTM isolated from symptomatic TB negative patients in Kenya.

Keywords: Nontuberculous mycobacteria; aminoglycosides; macrolides; rapid-growing mycobacteria; rifampicin; slow-growing mycobacteria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoglycosides* / pharmacology
Aminoglycosides* / therapeutic use
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Cross-Sectional Studies
Humans
Kenya
Macrolides / pharmacology
Macrolides / therapeutic use
Mutation
Nontuberculous Mycobacteria / genetics
Rifampin* / pharmacology
Rifampin* / therapeutic use

Substances

Aminoglycosides
Rifampin
Macrolides
Anti-Bacterial Agents

Associated data

figshare/10.6084/m9.figshare.20331378.v2

Grants and funding

This work was supported by the Meru University of Science and Technology 6th call for proposals awarded to Zakayo M Mwangi. The content is solely the responsibility of the authors and does not represent the views of the funders.