Antibiotic resistance by high-level intrinsic suppression of a frameshift mutation in an essential gene.

ABSTRACT: A fundamental feature of life is that ribosomes read the genetic code in messenger RNA (mRNA) as triplets of nucleotides in a single reading frame. Mutations that shift the reading frame generally cause gene inactivation and in essential genes cause loss of viability. Here we report and characterize a +1-nt frameshift mutation, centrally located in rpoB, an essential gene encoding the beta-subunit of RNA polymerase. Mutant Escherichia coli carrying this mutation are viable and highly resistant to rifampicin. Genetic and proteomic experiments reveal a very high rate (5%) of spontaneous frameshift suppression occurring on a heptanucleotide sequence downstream of the mutation. Production of active protein is stimulated to 61-71% of wild-type level by a feedback mechanism increas

SUBMITTER: Huseby DL 

PROVIDER: S-EPMC7022156 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature