Replacement of S14 protein in ribosomes of zinc-starved mycobacteria reduces spectinamide sensitivity.

We report here that while Mpy binding has no significant effect on Spa sensitivity to the ribosome, replacement of S14c+ with its C- counterpart reduces the binding affinity of the drug by ∼2-fold, causing increased Spa tolerance in Mycobacterium smegmatis and Mycobacterium tuberculosis cells harboring the C- ribosome. The altered interaction between Spa and ribosomes likely results from new contact points for D67 and R83 residues of S14c- with U1138 and C1184 of 16S rRNA helix 34, respectively. Given that M. tuberculosis induces ribosome remodeling during progression from acute to chronic phase of a lung infection, our findings highlight new considerations in the development of Spa as effective drugs against TB. PMID: 33361293 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research