Uropathogenic Escherichia coli CFT073 is adapted to acetatogenic growth but does not require acetate during murine urinary tract infection.
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.
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Andrew T
AT
Anfora
David K
DK
Halladin
Brian J
BJ
Haugen
Rodney A
RA
Welch
D000084:Acetate Kinase / Q000235:genetics / Q000378:metabolism; D000085:Acetates / Q000378:metabolism*; D000818:Animals; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010755:Organophosphates / Q000378:metabolism; D010709:Phosphate Acetyltransferase / Q000235:genetics / Q000378:metabolism; D014552:Urinary Tract Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D014774:Virulence / Q000235:genetics
D000085:Acetates; D010755:Organophosphates; C011632:acetyl phosphate; D010709:Phosphate Acetyltransferase; D000084:Acetate Kinase