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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2016)

Cigarette smoking is one of the leading preventable causes of death in the United States. It is well recognized that cigarette smoking alters the human defense mechanism, and increases susceptibility to bacterial infections and diseases, such as pneumonia and chronic obstructive pulmonary disease. However, the effects of cigarette smoke on the pathogenic aspect of this human-pathogen dynamic remains poorly understood. Therefore, we sought to determine the effects of cigarette smoke on the pathogenicity properties of Pseudomonas aeruginosa (PSA), a prominent airway pathogen in adult smokers. Here, we show that while cigarette smoke exposure slows PSA growth in a dose-dependent manner, it increases certain pathogenicity factors. PSA exposed to cigarette smoke extract (CSE) showed increased resistance to killing by reactive oxygen species, suggesting that cigarette smoke may aid in the survival of PSA in phagolysosomes, a principal innate immune antimicrobial mechanism. When human neutrophils were infected with PSA, cigarette smoke exposure increased resistance to neutrophil killing, with 100% of CSE-PSA surviving, while 20% of control PSA was killed. Furthermore, we discovered that a long-term CSE exposure causes a more dramatic inhibition in PSA growth, compared to PSA with one time CSE exposure; this suggests that the PSA population in long-term smokers may possess different virulence properties than their sporadic/non-smoker counterparts. We conclude that cigarette smoke-induced resistance phenotypes in pathogens may be an important contributor to the vulnerability of cigarette smokers to infectious airway diseases. We hope our findings will improve our understanding of the effects of cigarette smoke on human health.

    Cover page: Alterations in Pathogenicity Factors of Pseudomonas aeruginosa in Response to Cigarette Smoke Exposure
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2020)
    It is widely known that cigarette smoke damages host defenses and increases susceptibility to bacterial infections. Pseudomonas aeruginosa, a Gram-negative bacterium that commonly colonizes the airways of smokers and patients with chronic lung disease, can cause pneumonia and sepsis and can trigger exacerbations of lung diseases. Pseudomonas aeruginosa colonizing airways is consistently exposed to inhaled cigarette smoke. Here, we investigated whether cigarette smoke alters the ability of this clinically significant microbe to bypass host defenses and cause invasive disease. We found that cigarette smoke extract (CSE) exposure enhances resistance to human neutrophil killing, but this increase in pathogenicity was not due to resistance to neutrophil extracellular traps. Instead, Pseudomonas aeruginosa exposed to CSE (CSE-PSA) had increased resistance to oxidative stress, which correlated with increased expression of tpx, a gene essential for defense against oxidative stress. In addition, exposure to CSE induced enhanced biofilm formation and resistance to the antibiotic levofloxacin. Finally, CSE-PSA had increased virulence in a model of pneumonia, with 0% of mice infected with CSE-PSA alive at day 6, while 28% of controls survived. Altogether, these data show that cigarette smoke alters the phenotype of P. aeruginosa, increasing virulence and making it less susceptible to killing by neutrophils and more capable of causing invasive disease. These findings provide further explanation of the refractory nature of respiratory illnesses in smokers and highlight cigarette smoking as a potential driver of virulence in this important airway pathogen.
      Cover page: Cigarette Smoke Exposure Promotes Virulence of Pseudomonas aeruginosa and Induces Resistance to Neutrophil Killing
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