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Journal of Genetics

, Volume 96, Issue 4, pp 599–612 | Cite as

Fitness-compensatory mutations facilitate the spread of drug-resistant F15/LAM4/KZN and F28 Mycobacterium tuberculosis strains in KwaZulu-Natal, South Africa

  • Charissa C. Naidoo
  • Manormoney PillayEmail author
Research Article

Abstract

While the acquisition of drug resistance is often accompanied by fitness costs, Mycobacterium tuberculosis has developed mechanisms to overcome these costs in the form of compensatory mutations. In an attempt to dissect strain-specific differences in biological fitness, 10 M. tuberculosis genomes, representing F15/LAM4/KZN, Beijing, F11 and F28 genotypes were sequenced on the Illumina MiSeq platform. Drug-susceptible F15/LAM4/KZN strains differed by 43 SNPs, demonstrating that heterogeneity exists even among closely-related strains. We found unique, nonsynonymous single-nucleotide polymorphisms (SNPs) in the sigA and grcC1 genes of multidrug resistant (MDR) and XDR F15/LAM4/KZN strains, respectively. The F28 MDR strain harboured a novel ubiA mutation in combination with its embB M306I mutation, which may be related to ethambutol resistance. In addition, it possessed a low-frequency rpoC mutation, suggesting that this strain was in the process of developing compensation. In contrast, no compensatory mutations were identified in Beijing and F11 MDR strains, corroborating its low in vitro fitness. Clinical strains also harboured unique SNPs in a number of important genes associated with virulence, highlighting the need for future studies which examine the correlation of genetic variations with phenotypic diversity. In summary, whole-genome sequencing revealed the presence of fitness-compensatory mutations in F15/LAM4/KZN and F28 genotypes which predominate in MDR and/or extensively drug resistant (XDR) forms in KwaZulu-Natal, South Africa.

Keywords

whole-genome sequencing Illumina MiSeq single-nucleotide polymorphisms CLC genomics workbench drug resistance Mycobacterium tuberculosis 

Notes

Acknowledgements

This study was supported by the National Research Foundation of South Africa (Grant no. 88959 and 90508) and the College of Health Sciences, University of KwaZulu-Natal.

Supplementary material

12041_2017_805_MOESM1_ESM.pdf (311 kb)
Supplementary material 1 (pdf 311 KB)

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Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  1. 1.Medical Microbiology and Infection Control, School of Laboratory Medicine and Medical SciencesUniversity of KwaZulu-NatalCongellaSouth Africa
  2. 2.DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis ResearchDivision of Molecular Biology and Human Genetics, Faculty of Medicine and Health SciencesCape TownSouth Africa

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