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

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Antibiotic resistance in Staphylococcus aureus (MRSA and MSSA) poses a significant global health threat.
• Programmed cell death (PCD) pathways in bacteria are increasingly recognized as targets for antimicrobial strategies.
• Extracellular death factor (EDF) from Escherichia coli has shown potential in modulating bacterial viability.

Purpose of the Study:

• To investigate the role of extracellular death factor (EDF) from Escherichia coli in inducing programmed cell death (PCD) in methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA).
• To explore the potential of EDF as a non-antibiotic therapeutic candidate against antibiotic-resistant pathogens.

Main Methods:

• Bacterial strain confirmation and minimum inhibitory concentration (MIC) testing following CLSI guidelines.
• Extraction and efficacy determination of EDF, CFU assessment, and Real-time PCR for mazE and mazF gene expression analysis.
• Evaluation of persister cell formation and EDF synthesis in aged bacterial cultures.

Main Results:

• The combination of E. coli-derived EDF and sub-minimum inhibitory concentration (sub-MIC) rifampin reduced MRSA and MSSA CFUs.
• EDF treatment significantly increased the expression of the mazF gene over the mazE gene in MRSA and MSSA.
• EDF was synthesized in old cultures of MRSA and MSSA, with E. coli 25922 supernatant showing higher efficacy.

Conclusions:

• EDF derived from E. coli, particularly in conjunction with sub-MIC rifampin, can induce PCD in MRSA and MSSA via MazEF system activation.
• EDF demonstrates potential as a novel, non-antibiotic therapeutic agent for combating infections caused by antibiotic-resistant Staphylococcus aureus.
• Further research is warranted to fully elucidate and exploit EDF's therapeutic potential.