Sunday, December 22, 2024
12/22/2024
Project Summary Cystic fibrosis (CF) is a genetic disease that results in persistent and chronic lung infections which reduce lung function over time. Pseudomonas aeruginosa (Pa), an opportunistic bacterial pathogen that infects patient’s lungs at a young age and persists throughout life, is a major contributing factor. Why antibiotic treatments against Pa ultimately fail remains unclear, but one plausible explanation is that the organism resides in spatially organized aggregates within the CF lung, where cells adapt to the host environment and evade immune responses and resist therapeutic interventions. It was recently shown that environmental factors such as host derived polymers (e.g. mucin & eDNA) influence the organization of bacterial aggregates, while changes in lipopolysaccharide (LPS) O-specific antigen (OSA) structure drives the formation of different aggregate-types and limit the physical impact of polymers due to alterations in cell surface hydrophobicity. This suggests a crucial interplay between cell surface properties and the physical features of the environment, which potentially sheds new light on the role of OSA in CF lungs in helping to enhance or reduce cooperative and competitive interactions between cells. This study will therefore focus on understanding how changes in LPS composition influences aggregate-type and cooperative interactions in heterogenous populations of Pa sourced from CF lungs. The main goals are to (i) determine the changes in frequency of Pa isolates with differential OSA structure in CF airways; (ii) investigate the role of LPS on cell surface hydrophobicity, aggregate assembly type and spatial organization of Pa populations; (iii) assess how aggregate-type and alginate production influence tolerance to antibiotics and (iv) evaluate the impact of spatial organization on social dynamics in Pa populations. The research described in this project will provide valuable insights into how the hydrophobicity of the bacterial cell surface which is dictated by the LPS-type, influences aggregate formation and social interactions. A deeper understanding of this will help inform as to how and why Pa variants co-exist in chronic infections and why social behaviors are maintained or lost. In the future, these ideas and findings can be extended to other social traits and microbiome studies involving multiple species.
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