Browsing by Subject "Polymicrobial"
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Item Ecology of Pseudomonas aeruginosa infections(2017-05) Dees, Justine Lynn; Whiteley, Marvin; Alper, Hal; Barrick, Jeffrey E.; Fast, Walter; Marcotte, Edward; Hunicke-Smith, ScottThe Gram-negative opportunistic pathogen Pseudomonas aeruginosa infects many different tissues types of immunocompromised individuals, especially the soft tissues and lungs. Despite the prevalence of P. aeruginosa in multiple infection environments, many of the mechanisms controlling this bacterium’s ability to thrive during infection remain unexplained. Therefore, I explored two facets of the ecology of P. aeruginosa infections: 1) the presence of co-infecting bacterial species and 2) the disturbance by antimicrobial treatment. The fitness-based genomic approach, Transposon sequencing (Tn-seq) was used to identify P. aeruginosa fitness determinants during chronic wound infection with the common co-infecting species, Staphylococcus aureus. The Tn-seq data revealed several genes that P. aeruginosa requires during co-infection with S. aureus. In particular, I demonstrated that the ability of P. aeruginosa to biosynthesize glutathione is a crucial determinant of P. aeruginosa fitness during chronic wound co-infection with S. aureus, potentially to relieve oxidative stress. To explore how the disturbance by antimicrobial treatment affects P. aeruginosa, I combined expression- (RNA sequencing) and fitness-based (Tn-seq) genomic techniques and identified genes involved in P. aeruginosa in vitro resistance to various antimicrobials.Item The effects of polymicrobial metabolism on pathogenesis and survival in Aggregatibacter actinomycetemcomitans(2011-08) Ramsey, Matthew M.; Whiteley, Marvin; Marcotte, Edward; Meyer, Richard; Trent, Stephen M.; Walker, JamesIn this dissertation I describe a model system to characterize the response of an oral bacterial pathogen, Aggregatibacter actinomycetemcomitans to the metabolic byproducts of a representative member of the oral flora, Streptococcus gordonii. A. actinomycetemcomitans is a causative agent of periodontal infections in humans. To cause infection, A. actinomycetemcomitans must overcome numerous challenges, including the host immune system and toxic metabolite production from other microbes. The most numerically dominant flora in the oral cavity are oral streptococci, which are well known for their ability to produce copious amounts of lactic acid and H₂O₂. By studying the response to H₂O₂ and lactic acid in pure and co-cultures, I have demonstrated that A. actinomycetemcomitans responds to these metabolites by several novel mechanisms that both enhance its survival in the presence of the host immune system and in the presence of the model oral streptococci S. gordonii. These studies have demonstrated that metabolites produced by normal flora can impact the survival of a single species in vivo as much as previously known virulence factors have done. In addition, I present a new method for measuring metabolite production in an attached cell population. This method is a novel application of scanning electrochemical microscopy (SECM) and I used this technique to study H₂O₂ production in the three dimensional space surrounding a multispecies biofilm in real time. In a related study I present the use of SECM to discover a novel redox chemistry phenomenon in the opportunistic pathogen Pseudomonas aeruginosa.