Differential expression of bacterial lipoproteins during S. aureus infection of C. elegans
Staphylococcus aureus is an extremely successful opportunistic bacterium capable of causing a wide range of hospital-acquired and community-acquired infections. It is becoming increasingly virulent and resistant to antibiotics. S. aureus expresses ~70 lipoproteins that function in substrate transport, sex pheromone biosynthesis, terminal electron transport, global gene regulation, but ~30% have no known function. C. elegans is a model host for studying the relationship between the animal innate immune system and bacterial and fungal pathogens. S. aureus-mediated infections of C. elegans were performed and gene expression studied by high-throughput RNA sequencing to investigate the host-pathogen relationship. S. aureus MRSA252 exhibited a high level of nematocidal activity: infected C. elegans showed visible signs of illness with a TD50 of approximately 1.5 days. Global transcriptomics identified 799 and 782 differentially expressed genes (DEGs) at 16 h and 40 h, respectively. A core set of 487 DEGs was shared across time points, while 307 genes were differentially regulated between early and late infection. Lpp expression was characterised by an overall downregulation; however, three lipoproteins were significantly upregulated at 40 h. Notably, SAR1402 (a phosphate-binding Lpp) transitioned from downregulation at 16 h to significant upregulation at 40 h, suggesting adaptive nutrient scavenging and stress tolerance. The late-stage transcriptome was further defined by a 75-gene signature involving host tissue degradation (e.g., nuclease SAR0847). These results highlight the dynamic reprogramming of the staphylococcal surface and metabolism during the transition from colonisation to persistence in a nematode host and may inform the identification of novel targets for therapeutic intervention.