Genome-Wide Survey of Pseudomonas aeruginosa PA14 Reveals a Role for the Glyoxylate Pathway and Extracellular Proteases in the Utilization of Mucin

Infection and Immunity
Jeffrey M FlynnRyan C Hunter

Abstract

Chronic airway infections by the opportunistic pathogen Pseudomonas aeruginosa are a major cause of mortality in cystic fibrosis (CF) patients. Although this bacterium has been extensively studied for its virulence determinants, biofilm growth, and immune evasion mechanisms, comparatively little is known about the nutrient sources that sustain its growth in vivo Respiratory mucins represent a potentially abundant bioavailable nutrient source, although we have recently shown that canonical pathogens inefficiently use these host glycoproteins as a growth substrate. However, given that P. aeruginosa, particularly in its biofilm mode of growth, is thought to grow slowly in vivo, the inefficient use of mucin glycoproteins may be relevant to its persistence within the CF airways. To this end, we used whole-genome fitness analysis, combining transposon mutagenesis with high-throughput sequencing, to identify genetic determinants required for P. aeruginosa growth using intact purified mucins as a sole carbon source. Our analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway and amino acid biosynthetic machinery are required for mucin utilization. Secondary analyses confirmed the simultaneous liberation and co...Continue Reading

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Citations

Jan 7, 2018·Applied and Environmental Microbiology·Erika L EnglishMatthew J Wargo
Jan 9, 2020·Environmental Microbiology·José M Luengo, Elías R Olivera
Jan 8, 2020·Microbiology and Immunology·Yutaka KidaKoichi Kuwano
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Dec 12, 2020·Respiratory Research·Sebastián A Riquelme, Alice Prince
Mar 7, 2021·Drug Discovery Today·Martin J Everett, David T Davies

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