Affiliation:
1. Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA
Abstract
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 consumption of acetate during mucin degradation and revealed a central role for the extracellular proteases LasB and AprA. Together, these studies describe a molecular basis for mucin-based nutrient acquisition by
P. aeruginosa
and reveal a host-pathogen dynamic that may contribute to its persistence within the CF airways.
Funder
HHS | National Institutes of Health
HHS | NIH | National Center for Advancing Translational Sciences
HHS | NIH | National Heart, Lung, and Blood Institute
Cystic Fibrosis Foundation
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
22 articles.
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