PPE51 Is Involved in the Uptake of Disaccharides by Mycobacterium tuberculosis

We have recently found that selected -disaccharides possess bactericidal effects against but not against or S . Here, we selected spontaneous mutants displaying resistance against the investigated -glycoside. According to next-generation sequencing, four of six analyzed mutants which were resistant to high concentrations of the tested chemical carried nonsynonymous mutations in the gene encoding the PPE51 protein. The complementation of these mutants with an intact gene returned their sensitivity to the wild-type level. The uptake of tritiated -glycoside was significantly more abundant in wild-type compared to the strain carrying the mutated gene. The mutations or CRISPR-Cas9-mediated downregulation of PPE51 expression affected the growth of mutant strains on minimal media supplemented with disaccharides (maltose or lactose) but not with glycerol or glucose as the sole carbon and energy source. Taking the above into account, we postulate that PPE51 participates in the uptake of disaccharides by tubercle bacilli.