Outer membrane permeability barrier disruption by polymyxin in polymyxin-susceptible and -resistant Salmonella...

Area of Science:

• Microbiology
• Bacterial genetics
• Membrane biology

Background:

• Polymyxins are critical antibiotics targeting Gram-negative bacteria.
• Emergence of polymyxin resistance is a significant public health concern.
• The pmrA gene in Salmonella typhimurium is associated with polymyxin resistance.

Purpose of the Study:

• To investigate the impact of the pmrA mutation on the outer membrane properties of Salmonella typhimurium.
• To elucidate the mechanism by which pmrA confers polymyxin resistance.
• To assess the effect of the pmrA mutation on outer membrane permeability and susceptibility to lysis.

Main Methods:

• Comparative analysis of wild-type and pmrA mutant Salmonella typhimurium strains.
• Assessment of outer membrane permeability to macromolecules (lysozyme, periplasmic proteins).
• Evaluation of susceptibility to deoxycholate-induced lysis and gentian violet uptake.

Main Results:

• pmrA mutants maintained outer membrane integrity against polymyxin treatment, unlike susceptible parent strains.
• Higher polymyxin concentrations were required to sensitize pmrA mutants to deoxycholate lysis.
• The pmrA mutation specifically affected polymyxin susceptibility without altering gentian violet uptake.

Conclusions:

• The pmrA mutation confers polymyxin resistance by altering Salmonella typhimurium's outer membrane structure and function.
• This alteration reduces the outer membrane's susceptibility to polymyxin-mediated damage and lysis.
• The findings highlight the pmrA gene as a key factor in polymyxin resistance mechanisms in Gram-negative bacteria.