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Dissemination and systemic colonization of uropathogenic Escherichia coli in a murine model of bacteremia.

Smith SN, Hagan EC, Lane MC, Mobley HL - MBio (2010)

Bottom Line: UPEC was recovered from the spleen, liver, kidneys, lungs, heart, brain, and intestines as early as 20 min postinoculation, peaking at 24 h postinoculation.A nonpathogenic E. coli K-12 strain, however, disseminated at significantly lower levels (P < 0.01) and was cleared from the liver and cecum by 24 h postinoculation.Isogenic mutants lacking type 1 fimbriae, P fimbriae, capsule, TonB, the heme receptors Hma and ChuA, or particularly the sialic acid catabolism enzyme NanA were significantly outcompeted by wild-type CFT073 during bacteremia (P < 0.05), while flagellin and hemolysin mutants were not.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

ABSTRACT
Infection with uropathogenic Escherichia coli (UPEC), the causative agent of most uncomplicated urinary tract infections, proceeds in an ascending manner and, if left untreated, may result in bacteremia and urosepsis. To examine the fate of UPEC after its entry into the bloodstream, we developed a murine model of sublethal bacteremia. CBA/J mice were inoculated intravenously with 1 × 10(6) CFU of pyelonephritis strain E. coli CFT073 carrying a bioluminescent reporter. Biophotonic imaging, used to monitor the infection over 48 h, demonstrated that the bacteria disseminated systemically and appeared to localize at discrete sites. UPEC was recovered from the spleen, liver, kidneys, lungs, heart, brain, and intestines as early as 20 min postinoculation, peaking at 24 h postinoculation. A nonpathogenic E. coli K-12 strain, however, disseminated at significantly lower levels (P < 0.01) and was cleared from the liver and cecum by 24 h postinoculation. Isogenic mutants lacking type 1 fimbriae, P fimbriae, capsule, TonB, the heme receptors Hma and ChuA, or particularly the sialic acid catabolism enzyme NanA were significantly outcompeted by wild-type CFT073 during bacteremia (P < 0.05), while flagellin and hemolysin mutants were not.

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UPEC virulence factor mutants in a cochallenge model of bacteremia. The indicated isogenic mutants were mixed 1:1 with wild-type CFT073 (except for the ksl cochallenge, where CFT073Nal was used), and CBA/J mice (n = 8 to 20) were inoculated intravenously with 106 CFU. CIs are shown for bacterial recovery at 24 hpi in the (A) spleen and (B) liver. Bars indicate the medians, and the dashed line represents a theoretical CI of 1. *, P < 0.05.
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f5: UPEC virulence factor mutants in a cochallenge model of bacteremia. The indicated isogenic mutants were mixed 1:1 with wild-type CFT073 (except for the ksl cochallenge, where CFT073Nal was used), and CBA/J mice (n = 8 to 20) were inoculated intravenously with 106 CFU. CIs are shown for bacterial recovery at 24 hpi in the (A) spleen and (B) liver. Bars indicate the medians, and the dashed line represents a theoretical CI of 1. *, P < 0.05.

Mentions: Both a P fimbria-deficient strain (pap) and a type 1 fimbria phase locked-OFF strain that does not produce type 1 fimbriae (fim L-OFF) were outcompeted by wild-type CFT073 in the spleen and liver, indicating that fimbria-mediated adherence contributes to UPEC systemic colonization (Fig. 5). A K2 polysaccharide capsule mutant (ksl) found previously to exhibit increased serum susceptibility (7) was outcompeted by CFT073Nal in the spleen and liver also, indicating that capsule contributes to UPEC bacteremic fitness. In contrast, neither a nonmotile flagellin mutant (fliC) nor an alpha-hemolysin mutant (hlyD), both of which have been shown to contribute to UPEC urovirulence (5, 25), were significantly outcompeted by wild-type CFT073 in either tissue.


Dissemination and systemic colonization of uropathogenic Escherichia coli in a murine model of bacteremia.

Smith SN, Hagan EC, Lane MC, Mobley HL - MBio (2010)

UPEC virulence factor mutants in a cochallenge model of bacteremia. The indicated isogenic mutants were mixed 1:1 with wild-type CFT073 (except for the ksl cochallenge, where CFT073Nal was used), and CBA/J mice (n = 8 to 20) were inoculated intravenously with 106 CFU. CIs are shown for bacterial recovery at 24 hpi in the (A) spleen and (B) liver. Bars indicate the medians, and the dashed line represents a theoretical CI of 1. *, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2993011&req=5

f5: UPEC virulence factor mutants in a cochallenge model of bacteremia. The indicated isogenic mutants were mixed 1:1 with wild-type CFT073 (except for the ksl cochallenge, where CFT073Nal was used), and CBA/J mice (n = 8 to 20) were inoculated intravenously with 106 CFU. CIs are shown for bacterial recovery at 24 hpi in the (A) spleen and (B) liver. Bars indicate the medians, and the dashed line represents a theoretical CI of 1. *, P < 0.05.
Mentions: Both a P fimbria-deficient strain (pap) and a type 1 fimbria phase locked-OFF strain that does not produce type 1 fimbriae (fim L-OFF) were outcompeted by wild-type CFT073 in the spleen and liver, indicating that fimbria-mediated adherence contributes to UPEC systemic colonization (Fig. 5). A K2 polysaccharide capsule mutant (ksl) found previously to exhibit increased serum susceptibility (7) was outcompeted by CFT073Nal in the spleen and liver also, indicating that capsule contributes to UPEC bacteremic fitness. In contrast, neither a nonmotile flagellin mutant (fliC) nor an alpha-hemolysin mutant (hlyD), both of which have been shown to contribute to UPEC urovirulence (5, 25), were significantly outcompeted by wild-type CFT073 in either tissue.

Bottom Line: UPEC was recovered from the spleen, liver, kidneys, lungs, heart, brain, and intestines as early as 20 min postinoculation, peaking at 24 h postinoculation.A nonpathogenic E. coli K-12 strain, however, disseminated at significantly lower levels (P < 0.01) and was cleared from the liver and cecum by 24 h postinoculation.Isogenic mutants lacking type 1 fimbriae, P fimbriae, capsule, TonB, the heme receptors Hma and ChuA, or particularly the sialic acid catabolism enzyme NanA were significantly outcompeted by wild-type CFT073 during bacteremia (P < 0.05), while flagellin and hemolysin mutants were not.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

ABSTRACT
Infection with uropathogenic Escherichia coli (UPEC), the causative agent of most uncomplicated urinary tract infections, proceeds in an ascending manner and, if left untreated, may result in bacteremia and urosepsis. To examine the fate of UPEC after its entry into the bloodstream, we developed a murine model of sublethal bacteremia. CBA/J mice were inoculated intravenously with 1 × 10(6) CFU of pyelonephritis strain E. coli CFT073 carrying a bioluminescent reporter. Biophotonic imaging, used to monitor the infection over 48 h, demonstrated that the bacteria disseminated systemically and appeared to localize at discrete sites. UPEC was recovered from the spleen, liver, kidneys, lungs, heart, brain, and intestines as early as 20 min postinoculation, peaking at 24 h postinoculation. A nonpathogenic E. coli K-12 strain, however, disseminated at significantly lower levels (P < 0.01) and was cleared from the liver and cecum by 24 h postinoculation. Isogenic mutants lacking type 1 fimbriae, P fimbriae, capsule, TonB, the heme receptors Hma and ChuA, or particularly the sialic acid catabolism enzyme NanA were significantly outcompeted by wild-type CFT073 during bacteremia (P < 0.05), while flagellin and hemolysin mutants were not.

Show MeSH
Related in: MedlinePlus