Cigarette smoke exposure augments the ability ofStaphylococcus aureus to evade host innate immune responses. (INM3P.407)

Abstract

Abstract The nose is the most common reservoir for Staphylococcus aureus, which is present 30-40% of normal adults. Its presence in the nasopharynx varies with age, but greater in children than adults. The oxidant chemicals in cigarette smoke (CS) induce S. aureus biofilm formation by suppressing agr (accessory gene regulator) regulon. In addition to quorum sensing, agr regulon regulates virulence gene expression of S. aureus. Therefore, we hypothesized that CS exposure augments virulence of S. aureus by evading host immunity. Using RNAseq, S. aureus transcriptome analysis revealed upregulation of gene expression which includes the induction of effectors involved in the nasal colonization (clfB), survival inside macrophages (spa) and the escape from neutrophil extracellular traps (NETs; nuc). In accordance with the RNAseq data, CS-exposed S. aureus exhibited significantly reduced phagocytosis, improved intracellular survival, increased evasion NET-mediated killing in the in vitro assays using human and murine macrophages and neutrophils. Importantly, the mouse model of acute pneumonia by intranasal inoculation resulted in significantly increased pulmonary bacterial burden in mice infected with CS-exposed S. aureus as compared to those infected with control bacteria. These results, which are clinically relevant, support a novel paradigm that the normal microflora becomes hypervirulent following exposure to environmental stressors such as CS, leading to devastating infections in humans.