Inducing programmed cell death trough MazEF system to combat Staphylococcus aureus: A non-antibiotic treatment candidate.

The aim of the present study was to evaluate the role of extracellular death factor (EDF) derived from Escherichia coli in the induction of programmed cell death (PCD) in methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA). The confirmation of bacterial strains as well as the minimum inhibitory concentration (MIC) test were performed according to CLSI, 2022. The extraction and efficacy determination of EDF as well as the CFU assessment were done. The expression of mazE and mazF gens in different conditions was evaluated by Real-time PCR. The likely formation of persister cells from MRSA and MSSA, and the possible synthesis of EDF in old cultures of these pathogens was evaluated, as well. The combination of EDF of two E. coli strains and sub-MIC rifampin reduced the CFUs of MRSA and MSSA strains in mid-logarithmic growth phase while increased the expression of mazF several times more than mazE gene. The expression of these genes in different conditions were unlike. EDF was produced in the old cultures of MRSA and MSSA. The supernatant of E. coli 25922 was more powerful than the clinical strain ones to decrease the CFUs of the MRSA and MSSA. The EDF derived from E. coli in combination with sub-MIC rifampin could induce PCD in MRSA and MSSA through activation of the MazEF system. This phenomenon could be exploited as a non-antibiotic treatment candidate to combat the infections caused by the antibiotic-resistant pathogens. However, more studies should be performed in this regard.