Have compensatory mutations facilitated the current epidemic of multidrug-resistant tuberculosis?

Abstract

Compensatory mutations have been suggested to promote multidrug-resistant tuberculosis (MDR-TB) transmission, but their role in facilitating the recent transmission of MDR-TB is unclear. To investigate the epidemiological significance of compensatory mutations, we analyzed a four-year population-based collection of MDR-TB strains from Shanghai (the most populous city in China) and 1346 published global MDR-TB strains. We report that MDR-TB strains with compensatory mutations in the rpoA, rpoB, or rpoC genes were neither more frequently clustered nor found in larger clusters than those without compensatory mutations. Our results suggest that compensatory mutations are not a major contributor to the current epidemic of MDR-TB.

These authors contributed equally: Qingyun Liu, Tianyu Zuo.

These authors contributed equally: Qingyun Liu, Tianyu Zuo.

Acknowledgements

We are grateful to Dr. Ted Cohen for the helpful suggestions and discussion of this work. This study was funded by the National Science and Technology Major Project of China (2017ZX10201302 and 2018ZX10715012 to Q.G.), National Natural Science Foundation of China (91631301 & 81661128043 to Q.G., 81701975 to Q.L., and 81402727 to C.Y.), NSFC-BRICS grant (81761148027), Sanming project of Medicine in Shenzhen (SZSM201611030) and JSGG20170413142559220.

Authors’ contributions

Q.L., T.Z., and Q.G. designed and implemented the study. J.W. and G.Z. contributed the clinical M. tb isolates’ DNA. C.Y. conducted the MIRU-VNTR typing and analysis. P.X. conducted the Sanger sequencing. Q.L., T.Z., and M.G. analyzed the sequencing reads and performed the cluster analysis. Q.J. performed the statistical analysis. Q.L., T.Z., R.P., H.T., and Q.G. drafted the manuscript. All authors critically reviewed and approved the final version of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Information accompanies this paper at (10.1038/s41426-018-0101-6).

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