Scholarly Work - Microbiology & Cell Biology
Permanent URI for this collectionhttps://scholarworks.montana.edu/handle/1/3494
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Item Polyamines and linear DNA mediate bacterial threat assessment of bacteriophage infection(Proceedings of the National Academy of Sciences, 2023-02) de Mattos, Camilla D.; Faith, Dominick R.; Nemudryi, Artem; Schmidt, Amelia K.; Bublitz, DeAnna C.; Hammond, Lauren R.; Kinnersley, Margie; Schwartzkopf, Caleb M.; Robinson, Autumn J.; Joyce, Alex; Michaels, Lia A.; Brzozowski, Robert S.; Coluccio, Alison; Xing, Denghui David; Uchiyama, Jumpei; Jennings, Laura K.; Eswara, Prahathees; Wiedenheft, Blake; Secor, Patrick R.Monitoring the extracellular environment for danger signals is a critical aspect of cellular survival. However, the danger signals released by dying bacteria and the mechanisms bacteria use for threat assessment remain largely unexplored. Here, we show that lysis of Pseudomonas aeruginosa cells releases polyamines that are subsequently taken up by surviving cells via a mechanism that relies on Gac/Rsm signaling. While intracellular polyamines spike in surviving cells, the duration of this spike varies according to the infection status of the cell. In bacteriophage-infected cells, intracellular polyamines are maintained at high levels, which inhibits replication of the bacteriophage genome. Many bacteriophages package linear DNA genomes and linear DNA is sufficient to trigger intracellular polyamine accumulation, suggesting that linear DNA is sensed as a second danger signal. Collectively, these results demonstrate how polyamines released by dying cells together with linear DNA allow P. aeruginosa to make threat assessments of cellular injury.Item Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections(Frontiers Media SA, 2020-02) Secor, Patrick R.; Burgener, Elizabeth B.; Kinnersley, M.; Jennings, Laura K.; Roman-Cruz, Valery; Popescu, Medeea; Van Belleghem, Jonas D.; Haddock, Naomi; Copeland, Conner; Michaels, Lia A.; de Vries, Christiaan R.; Chen, Qingquan; Pourtois, Julie; Wheeler, Travis J.; Milla, Carlos E.; Bollyky, Paul L.Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.Item Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in Pseudomonas aeruginosa(Proceedings of the National Academy of Sciences, 2018-10) Secor, Patrick R.; Michaels, Lia A.; Ratjen, Anina; Jennings, Laura K.; Singh, Pradeep K.Bacteria causing chronic infections are generally observed living in cell aggregates suspended in polymer-rich host secretions, and bacterial phenotypes induced by aggregated growth may be key factors in chronic infection pathogenesis. Bacterial aggregation is commonly thought of as a consequence of biofilm formation; however the mechanisms producing aggregation in vivo remain unclear. Here we show that polymers that are abundant at chronic infection sites cause bacteria to aggregate by the depletion aggregation mechanism, which does not require biofilm formation functions. Depletion aggregation is mediated by entropic forces between uncharged or like-charged polymers and particles (e.g., bacteria). Our experiments also indicate that depletion aggregation of bacteria induces marked antibiotic tolerance that was dependent on the SOS response, a stress response activated by genotoxic stress. These findings raise the possibility that targeting conditions that promote depletion aggregation or mechanisms of depletion-mediated tolerance could lead to new therapeutic approaches to combat chronic bacterial infections.