Macrophage environment turns otherwise MccJ25-resistant Salmonella into sensitive

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Antimicrobial Peptides

Background:

• Microcin J25 (MccJ25) is an antibiotic peptide from E. coli.
• MccJ25 uptake in E. coli requires FhuA and inner membrane proteins.
• Salmonella Typhimurium is resistant to MccJ25 due to its FhuA protein.

Purpose of the Study:

• Investigate MccJ25 susceptibility of S. Typhimurium within macrophages.
• Determine the role of macrophage-like conditions (low pH, low Mg, iron deprivation) in MccJ25 resistance.
• Elucidate the mechanism of MccJ25 uptake in S. Typhimurium under acidic conditions.

Main Methods:

• Culturing S. Typhimurium and E. coli under various pH and nutrient conditions.
• Assessing bacterial susceptibility to MccJ25 and novobiocin.
• Analyzing changes in bacterial membrane permeability.

Main Results:

• S. Typhimurium becomes susceptible to MccJ25 within macrophages.
• Low pH, but not low magnesium or iron deprivation, confers MccJ25 susceptibility.
• Low pH also sensitizes S. Typhimurium to novobiocin, indicating increased membrane permeability.
• MccJ25 inhibits S. Typhimurium even after pre-incubation in acidic pH and subsequent neutral pH treatment.

Conclusions:

• Acidic conditions irreversibly alter bacterial membrane permeability, allowing unspecific MccJ25 uptake.
• Intracellular pathogenic bacteria resistant to MccJ25 in vitro may become susceptible in vivo.
• The MccJ25 action spectrum is broader than previously indicated by in vitro studies.