scholarly journals Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase

2013 ◽  
Vol 4 (2) ◽  
pp. 220-224 ◽  
Author(s):  
Fumika Yakushiji ◽  
Yuko Miyamoto ◽  
Yuki Kunoh ◽  
Reiko Okamoto ◽  
Hidemasa Nakaminami ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Antimicrobial Agents ◽  
Switch Region ◽  
Hybrid Type ◽  
Bacterial Rna

scholarly journals New target for inhibition of bacterial RNA polymerase: ‘switch region’

2011 ◽  
Vol 14 (5) ◽  
pp. 532-543 ◽  
Author(s):  
Aashish Srivastava ◽  
Meliza Talaue ◽  
Shuang Liu ◽  
David Degen ◽  
Richard Y Ebright ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Switch Region ◽  
Bacterial Rna

scholarly journals Identification and characterization of pleiotropic high-persistence mutations in the beta subunit of the bacterial RNA polymerase

2021 ◽  
Author(s):  
Lev Ostrer ◽  
Yinduo Ji ◽  
Arkady Khodursky
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Survival Rates ◽  
Beta Subunit ◽  
High Survival ◽  
Resistance Mutations ◽  
Switch Region ◽  
E Coli ◽  
Bacterial Rna ◽  
Survival Frequency

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.

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