Lack of association of novel mutation Asp397Gly in aftB gene with ethambutol resistance in clinical isolates of Mycobacterium tuberculosis

Astha Giri, Hassan Safi, Andrea Maurizio Cabibbe, Shraddha Gupta, Anshika Narang, Gaurav Tyagi, Kamal Shrivastava, Chanchal Kumar, Naresh Kumar Sharma, Subramanya Lingaraju, Alberto Trovato, Simone Battaglia, Daniela Maria Cirillo, Mridula Bose, David Alland, Mandira Varma-Basil

Research output: Contribution to journalArticle

Abstract

To discover additional genotypic indicators for ethambutol (EMB) resistant M. tuberculosis, we studied polymorphisms in arabinofuranosyl transferase encoding genes aftA (Rv3792), aftB (Rv3805) and aftC (Rv2673) in 38 EMB resistant and 34 EMB susceptible isolates from India and a repository established by the World Health Organization (WHO) Special Programme for Research and Training in Tropical Disease (TDR) by DNA sequencing. The results were correlated with the minimum inhibitory concentration (MIC) of EMB and mutations in embB (Rv3795). The most common non-synonymous polymorphism identified in aftB was Asp397Gly in 12/38 (31.6%) EMB resistant and 3/34 (8.8%) EMB susceptible isolates. Interestingly, 10/12 (83.3%) EMB resistant isolates with aftB Asp397Gly mutation also carried embB306, embB402 or embB497 mutations. Association of Asp397Gly polymorphism with EMB resistance was statistically significant (p 0.0216). However, overexpression of the mutant aftB in M. tuberculosis H37Rv did not exhibit any change in the MIC. Whole genome sequencing of a panel of Indian isolates and SNP cluster grouping (SCG) of TDR strains revealed an association between aftB mutation Asp397Gly and Beijing genotype or SCG2, a cluster group representing the Beijing genotype. To conclude, though aftBAsp397Gly mutation is not associated with EMB resistance, this mutation may be a phylogenetic marker for the Beijing clade.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalTuberculosis
Volume115
DOIs
Publication statusPublished - Mar 2019

Keywords

  • aftB
  • Beijing
  • Ethambutol resistance
  • Mycobacterium tuberculosis
  • SNPs

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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