MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters

Abstract

Background: Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and costs. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently, in a batch culture the late stationary phase is enriched with persistent bacteria. The mechanism of persister cell formation and its regulation is not well understood. Toxin-antitoxins (TA) systems have been implicated to be responsible for bacterial persistence and rifampicin is used to treat highly persistent bacterial strains. The current study tries to explore a possible interaction between rifampicin and the MazEF TA system that furthers the former’s success rate in treating persistent bacteria. Results: In the current study we found that the population of bacteria in the death phase of a batch culture consists of metabolically inactive live cells resembling persisters, which showed higher membrane depolarization as compared to the log phase bacteria. We also observed an increase in the expression of the MazEF TA modules in this phase. Since rifampicin is used to kill the persisters, we assessed the interaction of rifampicin with MazEF complex. We showed that rifampicin moderately interacts with MazEF complex with 1:1 stoichiometry.Conclusion: Our study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters.

The cell division protein ZapE is targeted by the antibiotic aztreonam to induce cell filamentation in Escherichia coli

“…The qRT-PCR was performed using a protocol already standardized in the laboratory [14]. Briefly, E. coli was treated with aztreonam (5 lM) for 120 min, cells were harvested and RNA was isolated using a RNA purification kit (Qiagen, Hilden, Germany).…”