Insights into the Staphylococcus aureus-Host Interface: Global Changes in Host and Pathogen Gene Expression in a Rabbit Skin Infection Model

• Published in: PloS one Vol. 10; no. 2; p. e0117713
• Main Authors: Malachowa, Natalia, Kobayashi, Scott D., Sturdevant, Daniel E., Scott, Dana P., DeLeo, Frank R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.02.2015; Public Library of Science (PLoS)
• Subjects: Abscesses; Animals; Bacteria; Carbon tetrachloride; CCL3 protein; CCR1 protein; Cell division; Cellulitis; Chemokines - genetics; Chemokines - metabolism; Cytokines; Deoxyribonucleic acid; DNA; DNA repair; Female; Fibrinogen; Fibronectin; Fibronectins; Gene expression; Genes; Genome, Bacterial; Gram-positive bacteria; Health aspects; Host-Pathogen Interactions; Human subjects; Humans; Infection; Infections; Infectious diseases; Inflammation; Interleukin 1; Interleukin 8; Interleukins - genetics; Interleukins - metabolism; Laboratories; Metabolism; Metabolites; Molecular chains; Neutrophils; Oncostatin M; Pathogenesis; Pathogens; Protein binding; Proteins; Rabbits; Skin; Staphylococcal Skin Infections - genetics; Staphylococcal Skin Infections - metabolism; Staphylococcal Skin Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - metabolism; Staphylococcus aureus - pathogenicity; Staphylococcus infections; Studies; Toxins; Transcriptome; Up-Regulation; Virulence; Virulence factors; Virulence Factors - genetics; Virulence Factors - metabolism; United States > US; Montana
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117713

Staphylococcus aureus is an important cause of human skin and soft tissue infections (SSTIs) globally. Notably, 80% of all SSTIs are caused by S. aureus, of which ∼63% are abscesses and/or cellulitis. Although progress has been made, our knowledge of the host and pathogen factors that contribute to the pathogenesis of SSTIs is incomplete. To provide a more comprehensive view of this process, we monitored changes in the S. aureus transcriptome and selected host proinflammatory molecules during abscess formation and resolution in a rabbit skin infection model. Within the first 24 h, S. aureus transcripts involved in DNA repair, metabolite transport, and metabolism were up-regulated, suggesting an increase in the machinery encoding molecules involved in replication and cell division. There was also increased expression of genes encoding virulence factors, namely secreted toxins and fibronectin and/or fibrinogen-binding proteins. Of the host genes tested, we found that transcripts encoding IL-8, IL1β, oncostatin M-like, CCR1, CXCR1 (IL8RA), CCL4 (MIP-1β) and CCL3 (MIP1α)-like proteins were among the most highly up-regulated transcripts during S. aureus abscess formation. Our findings provide additional insight into the pathogenesis of S. aureus SSTIs, including a temporal component of the host response. These results serve as a springboard for future studies directed to better understand how/why mild or moderate SSTIs progress to invasive disease.