Acetyl-proteome profiling of Staphylococcus aureus revealed lysine acetylation in bacterial antibiotic resistance

ABSTRACT: Protein post-translational modifications (PTMs) play crucial roles in various biological processes across prokaryotes and eukaryotes. Lysine acetylation (Kac), which is observed in different bacteria species and is known to be a dynamic and reversible PTM involved in numerous physiological functions. However, limited research has been conducted to explore the connection between Kac and bacterial antibiotic resistance. In this investigation, we employed advanced 4D label-free quantitative proteomics technology to examine the differential expression of Kac-modified proteins in Staphylococcus aureus strains: one susceptible to erythromycin (Ery-S) and another induced to be resistant (Ery-R). Our systematic analysis identified a total of 1808 acetylated proteins with 6791 specific Kac sites. Notably, we quantified 1907 of these sites across 483 proteins. A total of 548 Kac sites were affected by erythromycin pressure on 316 acetylated proteins. Functional analyses uncovered a notable presence of differentially acetylated proteins (DAPs) within pathways associated with ribosome assembly, glycolysis, and lysine biosynthesis. Moreover, our findings indicate a significant acetylation of ribosomal proteins in antibiotic-resistant strains, implying a potential regulatory role of this modification in translation processes. Further investigations using polysome profiling experiments revealed that Kac modification of ribosomal and ribosome-associated proteins can maintain translation in response to antibiotic stress. Our data provides support for the link between protein lysine acetylation and bacterial antibiotic resistance, highlighting the potential involvement of ribosome translation. These findings collectively unveil a novel mechanism that enhances our understanding of bacterial antibiotic resistance and offer valuable insights for the development of antibiotic treatment strategies.

INSTRUMENT(S): timsTOF

ORGANISM(S): Staphylococcus Aureus

TISSUE(S): Cell Culture

SUBMITTER: Miao Feng  

LAB HEAD: Miao Feng

PROVIDER: PXD043277 | Pride | 2024-10-17

REPOSITORIES: pride