Affiliation:
1. Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706
Abstract
ABSTRACT
In vivo accumulation of
d
-serine by
Escherichia coli
CFT073 leads to elevated expression of PAP fimbriae and hemolysin by an unknown mechanism. Loss of
d
-serine catabolism by CFT073 leads to a competitive advantage during murine urinary tract infection (UTI), but loss of both
d
- and
l
-serine catabolism results in attenuation. Serine is the first amino acid to be consumed in closed tryptone broth cultures and precedes the production of acetyl phosphate, a high-energy molecule involved in intracellular signaling, and the eventual secretion of acetate. We propose that the colonization defect associated with the loss of serine catabolism is due to perturbations of acetate metabolism. CFT073 grows more rapidly on acetogenic substrates than does
E. coli
K-12 isolate MG1655. As shown by transcription microarray results,
d
-serine is catabolized into acetate via the phosphotransacetylase (
pta
) and acetate kinase (
ackA
) genes while downregulating expression of acetyl coenzyme A synthase (
acs
). CFT073
acs
, which is unable to reclaim secreted acetate, colonized mouse bladders and kidneys in the murine model of UTI indistinguishably from the wild type. Both
pta
and
ackA
are involved in the maintenance of intracellular acetyl phosphate. CFT073
pta
and
ackA
mutants were screened to investigate the role of acetyl phosphate in UTI pathogenesis. Both single mutants are at a competitive disadvantage relative to the wild type in the kidneys but normally colonize the bladder. CFT073
ackA pta
was attenuated in both the bladder and the kidneys. Thus, we demonstrate that CFT073 is adapted to acetate metabolism as a result of requiring a proper cycling of the acetyl phosphate pathway for colonization of the upper urinary tract.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
38 articles.
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