title: Insights into the Staphylococcus aureus-host interface: global changes in host and pathogen gene expression in a rabbit skin infection model.
abstract: 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.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malachowa
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.affiliation: Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.affiliation: Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Scott
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013207:Staphylococcal Skin Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D059467:Transcriptome; D015854:Up-Regulation; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D007378:Interleukins; D037521:Virulence Factors