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

BMC Molecular and Cell Biology

Nimai Charan Mahanandia¹  Bharat Bhusan Subudhi²  Tushar Kant Beuria³  Cyrus Alexander⁴  Sunanda Mallick⁴  Pinkilata Pradhan⁵  Ankeeta Guru⁵ 

[1] Animal Biotechnology Centre, National Dairy Research Institute, Harya, – 132001, Karnal, India;Drug Development and Analysis, School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan Deemed to be University, Bhubaneswar, India;Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, India;Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, India;Manipal Academy of Higher Education, 576104, Manipal, Karnataka, India;Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, India;Regional Centre for Biotechnology, 121001, Faridabad, Haryana, India;

关键词: TA system;    MazEF;    Rifampicin;    Bacterial persistence;   

DOI  :  10.1186/s12860-020-00316-8

来源: Springer

【 摘 要 】

BackgroundPersistence 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 cost. 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-antitoxin (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.ResultsIn 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.ConclusionOur study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters.

【 授权许可】

CC BY