Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health concern due to its ability to evade antibiotics. Serine-threonine kinase 1 (Stk1) has previously been shown to play an important role in antibiotic resistance in S. aureus, which is why current research focuses on the development novel Stk1 inhibitors. However, very few substrates of Stk1 have been identified to date. Alterations to Stk1-mediated protein phosphorylation patterns can be used for the identification of Stk1 substrates. The small molecule adjuvant was synthesized and analyzed as a lead Stk1 inhibitor in these experiments. We hypothesized that by comparing phosphoproteins present in S. aureus cultures treated with the adjuvant, the antibiotic oxacillin, and cotreatment with both, we could identify novel Stk1 substrates. Proteins were subjected to trypsin digestion, phosphopeptide enrichment, and nanoliquid chromatography - tandem mass spectroscopy to reveal the identity of phosphoproteins. Finally, Proteome Discoverer was used to identify substrates which were no longer phosphorylated when Stk1 was inhibited by the novel adjuvant. Preliminary results will be presented. This work will add to our knowledge of virulence pathways utilized by this human pathogen and potentially lead to identifying novel drug targets.

Identifying serine-threonine kinase 1 substrates in MRSA with a phosphoproteome analysis.

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.