Analogs of the cationic C-terminal segments of human-β-defensins HBD1-3, Phd1-3 with a single disulfide bond, exhibited comparable antimicrobial activity that was salt sensitive. They did not show hemolytic activity. In this study, N-terminal myristoylation was carried out on Phd1-3 to examine whether increasing hydrophobicity would result in improved antibacterial activity. The antibacterial activity of the oxidized myristoylated peptides MPhd1-3 and their reduced forms MPhd1r-3r was determined. These peptides showed enhanced antibacterial activity as compared to Phd1-3, on mid-log phase and stationary phase of Staphylococcus aureus and Escherichia coli, except MPhd1r-3r that were inactive on stationary-phase E. coli. In the presence of 150 mm NaCl, MPhd1-3 showed activity against S. aureus. MPhd1and two exhibited activity against E. coli but MPhd3 was inactive. Zeta potential measurements indicated that MPhd1-3 were more effective in surface charge neutralization of bacteria as compared to Phd1-3. MPhd1-3 exhibited hemolytic activity to varying extents with MPhd1 being most hemolytic. The data indicate that myristoylation enhances antibacterial activity and modulates hemolytic activity to different extents. Apart from hydrophobicity, distribution of cationic residues in MPhd1-3 plays important roles for these activities.
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 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.
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 increase in disease incidences and persistent Chikungunya virus (CHIKV)-induced arthritis have been a huge burden on public health globally. In the absence of specific antivirals or vaccines, it is essential to continue efforts to develop effective anti-CHIKV strategies.
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