Proteomic and Membrane Lipid Correlates of Re-duced Host Defense Peptide Susceptibility in a <em>snoD</em> Mutant of <em>Staphylococcus aureus</em>

• Main Authors: Christian Kohler, Richard A. Proctor, Arnold S. Bayer, Michael R. Yeaman, Michael Lalk, Susanne Engelmann, Nagendra N. Mishra
• Format: Article
• Language: English
• Published: MDPI AG 2019-09-01
• Series: Antibiotics
• Subjects: <i>s. aureus</i>; snod mutant; lipids; proteomics; tpmp resistance
• Online Access: https://www.mdpi.com/2079-6382/8/4/169

We previously described a transposon mutant in <i>Staphylococcus aureus</i> strain SH1000 that exhibited reduced susceptibility to cationic thrombin-induced platelet microbicidal proteins (tPMPs). The transposon insertion site was mapped to the gene <i>snoD</i>, the staphylococcal <i>nuo</i> orthologue. Hence, further studies have been performed to understand how this mutation impacts susceptibility to tPMP, by comparing proteomics profiling and membrane lipid analyses of the parent vs. mutant strains. Surprisingly, the mutant showed differential regulation of only a single protein when cultivated aerobically (FadB), and only a small number of proteins under anaerobic growth conditions (AdhE, DapE, Ddh, Ald1, IlvA1, AgrA, Rot, SA2366, and SA2367). Corresponding to FadB impact on lipid remodeling, membrane fatty acid analyses showed that the <i>snoD</i> mutant contained more short chain anteiso-, but fewer short chain iso-branched chain fatty acids under both aerobic and anaerobic conditions vs. the parental strain. Based upon these proteomic and membrane compositional data, a hypothetical “network” model was developed to explain the impact of the <i>snoD</i> mutation upon tPMP susceptibility.