Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance.

ABSTRACT: Alteration of antibiotic binding sites through modification of ribosomal RNA (rRNA) is a common form of resistance to ribosome-targeting antibiotics. The rRNA-modifying enzyme Cfr methylates an adenosine nucleotide within the peptidyl transferase center, resulting in the C-8 methylation of A2503 (m⁸A2503). Acquisition of cfr results in resistance to eight classes of ribosome-targeting antibiotics. Despite the prevalence of this resistance mechanism, it is poorly understood whether and how bacteria modulate Cfr methylation to adapt to antibiotic pressure. Moreover, direct evidence for how m⁸A2503 alters antibiotic binding sites within the ribosome is lacking. In this study, we performed directed evolution of Cfr under antibiotic selection to generate Cfr variant

SUBMITTER: Tsai K 

PROVIDER: S-EPMC8752094 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature