title: Cigarette Smoke Extract-Exposed Methicillin-Resistant Staphylococcus aureus Regulates Leukocyte Function for Pulmonary Persistence.
abstract: Cigarette smoke (CS) predisposes exposed individuals to respiratory infections not only by suppressing immune response but also by enhancing the virulence of pathogenic bacteria. As per our observations, in methicillin-resistant Staphylococcus aureus strain USA300, CS extract (CSE) potentiates biofilm formation via the down-regulation of quorum-sensing regulon accessory gene regulator. Because accessory gene regulator is a global regulator of the staphylococcal virulome, in the present study we sought to identify the effects of CS exposure on staphylococcal gene expression using RNAseq. Comparative analysis of RNAseq profiles revealed the up-regulation of important virulence genes encoding surface adhesins (fibronectin- and fibrinogen-binding proteins A and B and clumping factor B) and proteins involved in immune evasion, such as staphylocoagulase, staphylococcal protein A, and nuclease. In concurrence with the RNAseq data, we observed: (1) significant up-regulation of the ability of CSE-exposed USA300 to evade phagocytosis by macrophages and neutrophils, a known function of staphylococcal protein A; and (2) twofold higher (P < 0.001) number of CSE-exposed USA300 escaping neutrophil extracellular trap-mediated killing by neutrophils as a result of CS-mediated induction of nuclease. Importantly, in three different mouse strains, C57BL6/J, Balb/C, and A/J, we observed significantly higher pulmonary bacterial burden in animals infected with CSE-exposed USA300 as compared with medium-exposed control USA300. Taken together, these observations indicate that bioactive chemicals in CS induce hypervirulence by augmenting the ability of USA300 to evade bactericidal functions of leukocytes, such as phagocytosis and neutrophil extracellular trap-mediated killing.
authors.affiliation: 1 Laboratory of Lung Biology, Department of Pathobiological Sciences, and.
authors.forename: Ritwij
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: 2 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, Louisiana.
authors.forename: John
authors.initials: J
authors.lastname: Caskey
authors.affiliation: 1 Laboratory of Lung Biology, Department of Pathobiological Sciences, and.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: 1 Laboratory of Lung Biology, Department of Pathobiological Sciences, and.
authors.forename: Sagar
authors.initials: S
authors.lastname: Paudel
authors.affiliation: 1 Laboratory of Lung Biology, Department of Pathobiological Sciences, and.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Baral
authors.affiliation: 1 Laboratory of Lung Biology, Department of Pathobiological Sciences, and.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schexnayder
authors.affiliation: 2 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, Louisiana.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: 2 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, Louisiana.
authors.forename: Nayong
authors.initials: N
authors.lastname: Kim
authors.affiliation: 3 Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Beata
authors.initials: B
authors.lastname: Kosmider
authors.affiliation: 4 Departments of Pediatrics and Microbiology, New York University School of Medicine, New York, New York; and.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
authors.affiliation: 1 Laboratory of Lung Biology, Department of Pathobiological Sciences, and.|5 Section of Pulmonary and Critical Care, Department of Medicine, LSU Health Sciences Center, New Orleans, Louisiana.
authors.forename: Samithamby
authors.initials: S
authors.lastname: Jeyaseelan
keywords: Staphylococcus aureus; USA300; cigarette smoke; nuclease; virulence