We have recently found that thiodisaccharides and thioglycosides present the bactericidal effect against Mycobacterium tuberculosis but not against Escherichia coli and Staphylococcus aureus. Here, we have selected spontaneous mutants displaying resistance against investigated thiosugars. As identified by next generation sequencing four of six analyzed mutants, resistant to high concentrations of the tested chemicals, carried nonsynonymous mutations in the ppe51 gene (named after their N-terminal Pro-Pro-Glu (PPE) motifs). The complementation of these mutants with an intact ppe51gene brought back their sensitivity to the wild type level. The uptake of tritriated thiodisaccharide was significantly more abundant by wild type M. tuberculosis comparing to the strain carrying mutated ppe51 gene. We also observed the in vitro binding of tritriated thiodisaccharide to the recombined PPE51 purified from E. coli but not to the control protein. The ppe51 mutations or CRISPR-Cas9 downregulation of PPE51 expression affected the growth of mutant strains on minimal media supplemented with glycerol or glucose as the only source of carbon and energy. Taking the above into account, we postulate the participation of PPE51 protein in the uptake of sugar derivatives by tubercle bacilli.

PPE51 is involved in the uptake of thiodisaccharides by Mycobacterium tuberculosis

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.