A very complicated UTI: malakoplakia following E. coli urinary tract infection.

Malakoplakia is a rare inflammatory disorder believed to result from a defect in macrophage phagocytic function triggering a granulomatous reaction. It can present with genitourinary, gastrointestinal, or cutaneous manifestations in immunocompromised or, less commonly, immunocompetent hosts. We describe a case of renal malakoplakia in a young, otherwise healthy patient presenting with nephromegaly and sepsis following an E. coli urinary tract infection. We discuss diagnosis and management, including antibiotic selection and the decision to pursue nephrectomy. This case highlights the potential for kidney recovery with prolonged antibiotic therapy in conjunction with adjunct immunomodulatory therapies and source control.

The impact of inactivation of the purine biosynthesis genes, purN and purT, on growth and virulence in uropathogenic E. coli.

De novo synthesis of purines has been suggested to be an important factor for the pathogenesis of uropathogenic E. coli (UPEC). We analyzed the role of the redundant purine biosynthesis genes purN and purT, responsible for the third step in the purine biosynthesis, during UPEC infection. Growth experiments in M9 (minimal media), MOPS (rich media), filtered urine, and human serum with E. coli UTI89 and ΔpurN, ΔpurT, and ΔpurN/T mutants revealed that UPEC relies on de novo purine synthesis for growth in minimal medium. Mutants in individual genes as well as the double mutant grew equally well as the wild type in urine, rich media, and serum. However, during competition for growth in urine, the wild type UTI89 strain significantly outcompeted the purine auxotrophic ΔpurN/T mutant from late exponential growth phase. Inactivation of purN and/or purT significantly affected UPEC invasion of human bladder cells, but not the intracellular survival. Cytotoxicity levels to bladder cells were also diminished when both purN and purT were deleted, while single gene mutants did not differ from the wild type. When infecting human macrophages, no differences were observed between UTI89 and mutants in uptake, survival or cytotoxicity. Finally, the lack of the pur-gene(s), whether analysed as single or double gene knock-out, did not affect recovery rates after in vivo infection in a mouse model of UTI. These findings suggest that de novo synthesis of purines might be required only when UPEC is fully deprived of nucleotides and when grown in competition with other microorganisms in urine.

Uropathogenic Escherichia coli Express Type 1 Fimbriae Only in Surface Adherent Populations Under Physiological Growth Conditions.

BACKGROUND: Most uropathogenic Escherichia coli (UPEC) strains harbor genes encoding adhesive type 1 fimbria (T1F). T1F is a key factor for successful establishment of urinary tract infection. However, UPEC strains typically do not express T1F in the bladder urine, and little is understood about its induction in vivo. METHODS: A flow chamber infection model was used to grow UPEC under conditions simulating distinct infection niches in the bladder. Type 1 fimbriation on isolated UPEC was subsequently determined by yeast cell agglutination and immunofluorescence microscopy, and the results were correlated with the ability to adhere to and invade cultured human bladder cells. RESULTS: Although inactive during planktonic growth in urine, T1F expression occurs when UPEC settles on and infects bladder epithelial cells or colonizes catheters. As a result, UPEC in these sessile populations enhances bladder cell adhesion and invasion potential. Only T1F-negative UPEC are subsequently released to the urine, thus limiting T1F expression to surface-associated UPEC alone. CONCLUSIONS: Our results demonstrate that T1F expression is strictly regulated under physiological growth conditions with increased expression during surface growth adaptation and infection of uroepithelial cells. This leads to separation of UPEC into low-expression planktonic populations and high-expression sessile populations.