Mutations conferring resistance to bactericidal antibiotics reduce average susceptibility of the mutant populations. It is unknown, however, how those mutations affect survival of individual bacteria. Since surviving bacteria can be a reservoir for recurring infections, it is important to know how survival rates may be affected by resistance mutations and by the choice of antibiotics. Here we present the evidence that: i)
Escherichia coli
mutants with 100-1000 times increased frequency of survival in ciprofloxacin, an archetypal fluoroquinolone antibiotic, can be readily obtained in a stepwise selection; ii) the high survival frequency is conferred by mutations in the switch region of the beta subunit of the RNA polymerase; iii) the switch-region mutations are (p)ppGpp mimics, partially analogous to
rpoB
stringent mutations; iv) the stringent and switch-region
rpoB
mutations frequently occur in clinical isolates of
E. coli
,
Acinetobacter baumannii
,
Mycobacterium tuberculosis
and
Staphylococcus aureus
, and at least one of them, RpoB S488L, which is a common rifampicin-resistance mutations, dramatically increases survival of a clinical MRSA strain in ampicillin; v) the RpoB-associated
high-survival
phenotype can be reversed by sub-inhibitory concentrations of chloramphenicol.
The RNA Polymerase “Switch Region” Is a Target for Inhibitors
