Trainee:

Sarah Council

Research Mentor:

Dr. Matthew Wolfgang, PhD

Clinical Co-mentor:

Dr. Richard Boucher, MD

Cystic Fibrosis (CF) is the most common lethal genetic disease amongst people of North Western European origin. From infancy into adulthood, CF patients experience a decline in lung function caused by persistent bacterial infection of the airways and unrelenting pulmonary inflammation eventually producing irreversible airway damage that ultimately leads to respiratory failure and death. Currently, clinicians use the results of aerobic sputum cultures and subsequent antibiotic susceptibility testing to guide CF treatment strategies. Lifelong aggressive antibiotic treatments for CF patients though, do not reflect a proportional patient survival rate because of a key gap of knowledge about the pathogenesis of CF, in particular the role of potentially pathogenic anaerobic bacteria. The occurrence of anaerobic niches in dehydrated mucus plugs in CF airways and non biased enumeration techniques have provoked a search for “strict” anaerobes and other bacterial species in CF airway mucus that are not considered classic CF pathogens and not detected by standard aerobic culture methods.

Recently in the Wolfgang lab, we have applied a culture independent molecular detection method to determine the spectrum of bacteria present in the airways of CF patients. We found that airway samples from CF patients harbor complex bacterial communities, consisting of typical aerobic pathogens (Pseudomonas aeruginosa) and a variety of anaerobic bacterial species, including the strict anaerobe Prevotella melaninogenica. P. melaninogenica is a gram-negative, capsulated anaerobic bacterium that is generally regarded as a member of the commensal flora of the mouth and gastrointestinal tract. Despite its commensal status, numerous studies have demonstrated that P. melaninogenica is capable of causing endogenous infections at numerous anatomical sites including the lung. P. melaninogenica is known to produce potential virulence factors including a fimbrial hemagglutin, β-lactamases and a wide-variety of proteases that could aid in this process.

The goal of my research is to determine whether the anaerobic bacterium, P. melaninogenica, contributes to CF disease pathogenesis by examining the organism’s ability to elicit CF-specific innate and adaptive immune responses. These proposed experiments, in addition to the rest of my thesis, would utilize relevant clinical samples and foster a basic science-clinical collaboration. Current therapy in CF does not typically include antibiotics directed against anaerobes, as such, the outcome of the proposed experiments could ultimately impact clinical practice.