Relationships Between Bactericidal Effect and Inhibition of Ribonucleic Acid Nucleotidyl-transferase by Rifampicin in Escherichia coli K-12

Abstract

The mechanism of action of rifampicin, an antibiotic which inhibits in vitro the polycondensation of ribonucleotides by ribonucleic acid (RNA) nucleotidyltransferase, was studied in vivo in Escherichia coli . It is argued that the inhibition of RNA nucleotidyltransferase represents the primary lesion and is responsible for the bactericidal effect. This conclusion is based on (i) the correlation between concentrations of the antibiotic which block in vivo incorporation of labeled uracil and the bactericidal concentrations, (ii) the evidence that the loss of viability of the cells immediately follows the block of RNA synthesis, and (iii) the observation that the reversal of the inhibition of RNA synthesis goes together with a reversal of the loss of viability.

Repositioning rifamycins for Mycobacterium abscessus lung disease

“…Discovered in 1965 [37,38], rifampicin remains a critical antibiotic in the treatment of TB infections. The drug targets the betasubunit of bacterial RNA polymerase (RpoB) [39][40][41] and has bactericidal activity [42][43][44]. Critically, rifampicin retains bactericidal activity against intra-macrophage [45] and (drug tolerant) nonreplicating bacteria [46].…”

Rifamycins: A General View

“…Apparently, a side chain linked to C-3 and/or to C-4 positions in creases the affinity of the molecule for the rifampicin-resistant RNA polymerase. Rifampicin exhibits bactericidal activity on Gram-positive and Gram-neg ative bacteria and on mycobacteria (57,58). Also, Chlamydozoaceae (tra choma agent), which are considered unusually small bacterial cells, are re ported to be inhibited by rifampicin and by some rifamycin SV derivatives (233).…”

“…Also, Chlamydozoaceae (tra choma agent), which are considered unusually small bacterial cells, are re ported to be inhibited by rifampicin and by some rifamycin SV derivatives (233). The primary target of rifampicin on whole bacteria is the synthesis of RNA (57,59). Following the addition of rifampicin, the rate of RNA syn thesis decreases exponentially with time after a short lag period.…”

Actions of the rifamycins.

“…Further in vivo studies with E. coli and B. subtilis clearly indicated that the inhibition of RNA synthesis is the primary action of the rifamycins and that their effect on protein and DNA synthesis is only a consequence of the inhibition of RNA synthesis (86,87,126). In the following subsections, a detailed account of the interactions between bacterial RNA polymerase and rifamycins will be given.…”