Preferential catabolism of l‐ vs d‐serine by Proteus mirabilis contributes to pathogenesis and catheter‐associated urinary tract infection

Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis ca...

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Published in:Molecular microbiology 2022-09, Vol.118 (3), p.125-144
Main Authors: Brauer, Aimee L., Learman, Brian S., Taddei, Steven M., Deka, Namrata, Hunt, Benjamin C., Armbruster, Chelsie E.
Format: Article
Language:English
Subjects:
amino acid
Amino acids
Biofilms
Biosynthesis
Catabolism
Catheters
Cell walls
Colonization
Critical components
D-Serine
Disruption
Fitness
Glutamine
Infections
L-Serine
Medical instruments
Membrane potential
Pathogenesis
Perturbation
Phenotypes
Phenylalanine
Proteus mirabilis
serine
Threonine
Tryptophan
Tyrosine
Urinary tract
Urinary tract diseases
urinary tract infection
Urinary tract infections
urine
Urogenital system
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Summary:Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter‐associated urinary tract infection (CAUTI), particularly those for d‐ and l‐serine. In this study, we sought to determine the hierarchy of amino acid utilization by P. mirabilis and to examine the relative importance of d‐ vs l‐serine catabolism for critical steps in CAUTI development and progression. Herein, we show that P. mirabilis preferentially catabolizes l‐serine during growth in human urine, followed by d‐serine, threonine, tyrosine, glutamine, tryptophan, and phenylalanine. Independently disrupting catabolism of either d‐ or l‐serine has minimal impact on in vitro phenotypes while completely disrupting both pathways decreases motility, biofilm formation, and fitness due to perturbation of membrane potential and cell wall biosynthesis. In a mouse model of CAUTI, loss of either serine catabolism system decreased fitness, but disrupting l‐serine catabolism caused a greater fitness defect than disrupting d‐serine catabolism. We, therefore, conclude that the hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract. Amino acids are a predominant nutrient in urine, and their import and catabolism has been hypothesized to contribute to the ability of bacteria to cause urinary tract infection. We demonstrate that a common uropathogen, Proteus mirabilis, preferentially catabolizes l‐serine followed by d‐serine, threonine, tyrosine, and glutamine during growth in human urine. We further demonstrate that l‐serine catabolism provides a greater fitness advantage than d‐serine catabolism, yet both pathways contribute to pathogenesis in the urinary tract.
ISSN:0950-382X
1365-2958
DOI:10.1111/mmi.14968