Transcription of Inflammatory Genes in the Lung after Infection with Community-Associated Methicillin-Resistant Staphylococcus aureus : a Role for Panton-Valentine Leukocidin?

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Abstract
Necrotizing pneumonia caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates is increasingly common and frequently severe. The early inflammatory response in the lung after CA-MRSA infection remains largely undefined. Additionally, many workers have hypothesized that the Panton-Valentine leukocidin (PVL) is a key virulence determinant in CA-MRSA necrotizing pneumonia. We hypothesized that intratracheal inoculation of rats with a USA300 CA-MRSA isolate would result in early expression of genes involved in the immune response and that this would correlate with inflammation and tissue destruction characteristic of necrotizing pneumonia. In addition, we hypothesized that infection with a PVL deletion mutant would result in an attenuated early host response. Infection of rats with a sublethal inoculum of USA300 (strain LAC) resulted in rapid increased expression of most cytokine, chemokine, and inflammatory receptor gene transcripts studied, as assessed by quantitative real-time reverse transcriptase PCR (qRT-PCR). The increased gene transcription was followed by inflammation, increased bacterial survival in the lungs, and necrotizing pneumonia. Infection with strain LAC and infection with strain LAC Δ pvl ( lukSF-PV deletion mutant) resulted in indistinguishable diseases, as assessed by mortality, in vivo bacterial recovery, and pulmonary pathology. Assessment of the transcription of inflammatory genes by qRT-PCR also revealed little difference after infection with LAC and after infection with LAC Δ pvl , either in animals that died or in animals that survived to 24 h after inoculation. We conclude that in a rat model of necrotizing pneumonia, there was an early, brisk inflammatory transcriptional response associated with neutrophil recruitment and tissue destruction. Deletion of lukSF-PV did not alter the early immune response to CA-MRSA in the lung.

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