Cigarette smoke increases Staphylococcus aureus biofilm formation via oxidative stress.
The strong epidemiological association between cigarette smoke (CS) exposure and respiratory tract infections is conventionally attributed to immunosuppressive and irritant effects of CS on human cells. Since pathogenic bacteria such as Staphylococcus aureus are members of the normal microbiota and reside in close proximity to human nasopharyngeal cells, we hypothesized that bioactive components of CS might affect these organisms and potentiate their virulence. Using Staphylococcus aureus as a model organism, we observed that the presence of CS increased both biofilm formation and host cell adherence. Analysis of putative molecular pathways revealed that CS exposure decreased expression of the quorum-sensing agr system, which is involved in biofilm dispersal, and increased transcription of biofilm inducers such as sarA and rbf. CS contains bioactive compounds, including free radicals and reactive oxygen species, and we observed transcriptional induction of bacterial oxidoreductases, including superoxide dismutase, following exposure. Moreover, pretreatment of CS with an antioxidant abrogated CS-mediated enhancement of biofilms. Exposure of bacteria to hydrogen peroxide alone increased biofilm formation. These observations are consistent with the hypothesis that CS induces staphylococcal biofilm formation in an oxidant-dependent manner. CS treatment induced transcription of fnbA (encoding fibronectin binding protein A), leading to increased binding of CS-treated staphylococci to immobilized fibronectin and increased adherence to human cells. These observations indicate that the bioactive effects of CS may extend to the resident microbiota of the nasopharynx, with implications for the pathogenesis of respiratory infection in CS-exposed humans.
Department of Pediatrics, Columbia University, New York, New York, USA.
Ritwij
R
Kulkarni
Swati
S
Antala
Alice
A
Wang
Fábio E
FE
Amaral
Ryan
R
Rampersaud
Samuel J
SJ
Larussa
Paul J
PJ
Planet
Adam J
AJ
Ratner
D018829:Adhesins, Bacterial / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D012907:Smoking / Q000009:adverse effects*; D013203:Staphylococcal Infections / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D014158:Transcription, Genetic; D014774:Virulence / Q000187:drug effects
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C078635:fibronectin-binding proteins, bacterial