Analysis of the Effects of Cigarette Smoke on Staphylococcal Virulence Phenotypes

Abstract

f Cigarette smoking is the leading preventable cause of death, disease, and disability worldwide. It is well established that cigarette smoke provokes inflammatory activation and impairs antimicrobial functions of human immune cells. Here we explore whether cigarette smoke likewise affects the virulence properties of an important human pathogen, Staphylococcus aureus, and in particular methicillin-resistant S. aureus (MRSA), one of the leading causes of invasive bacterial infections. MRSA colonizes the nasopharynx and is thus exposed to inhalants, including cigarette smoke. MRSA exposed to cigarette smoke extract (CSE-MRSA) was more resistant to macrophage killing (4-fold higher survival; P < 0.0001). CSE-MRSA demonstrated reduced susceptibility to cell lysis (1.78-fold; P ‫؍‬ 0.032) and antimicrobial peptide (AMP) (LL-37) killing (MIC, 8 M versus 4 M). CSE modified the surface charge of MRSA in a dose-dependent fashion, impairing the binding of particles with charge similar to that of AMPs by 90% (P < 0.0001). These changes persisted for 24 h postexposure, suggesting heritable modifications. CSE exposure increased hydrophobicity by 55% (P < 0.0001), which complemented findings of increased MRSA adherence and invasion of epithelial cells. CSE induced upregulation of mprF, consistent with increased MRSA AMP resistance. S. aureus without mprF had no change in surface charge upon exposure to CSE. In vivo, CSE-MRSA pneumonia induced higher mouse mortality (40% versus 10%) and increased bacterial burden at 8 and 20 h postinfection compared to control MRSA-infected mice (P < 0.01). We conclude that cigarette smoke-induced immune resistance phenotypes in MRSA may be an additional factor contributing to susceptibility to infectious disease in cigarette smokers.

Cigarette Smoke Extract–Exposed Methicillin-Resistant Staphylococcus aureus Regulates Leukocyte Function for Pulmonary Persistence

“…This is why we confirmed that CSE exposure induces hypervirulence in USA300 using several inbred mouse strains, including A/J and Balb/C. Furthermore, the resulting observations are similar to those from an outbred CD-1 mouse model, as previously reported (12). Taken together, these results confirm that, compared with the control, CSE-USA300 is hypervirulent in mice, regardless of their genetic background, as exhibited by increased pulmonary CFUs at 24 hours PI.…”

“…A recent publication reported that CSE exposure modifies the surface charge of USA300 and induces bacterial resistance to killing by antimicrobial peptides and macrophages, which results in a hypervirulence phenotype, in a CD-1 mouse model of pneumonia (12). In our present article, we extend the observations reported by McEachern and colleagues (12) and further delineate novel molecular mechanisms by which CS-exposed staphylococci may become hypervirulent in a vertebrate host.…”

“…In our present article, we extend the observations reported by McEachern and colleagues (12) and further delineate novel molecular mechanisms by which CS-exposed staphylococci may become hypervirulent in a vertebrate host.…”

Effects of Electronic (e)-Cigarette Vapor on Staphylococcal Virulence: Are E-Cigarettes Safer than Conventional Cigarettes?

“…In our studies, MRSA incubated with only nicotine produced more biofilm than control. In the exposure to either EV or CS, a novel pathway in inducing MRSA biofilm was suggested [23,29].…”

“…Our own studies demonstrate that CS extract (CSE) exposure results in a dose-dependent increase in MRSA surface hydrophobicity that is persistent and possibly even heritable [23,24]. Increased hydrophobicity is associated with increased bacterial interactions with host epithelial cells [25].…”