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Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse.

Becknell B, Mohamed AZ, Li B, Wilhide ME, Ingraham SE - PLoS ONE (2015)

Bottom Line: Bladder stones were analyzed by x-ray diffractometry.Bladders and kidneys were subject to histologic analysis.Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Section, Nationwide Children's Hospital, Columbus, OH, United States of America; Department of Pediatrics, Ohio State University School of Medicine, Columbus, OH, United States of America; Center for Clinical and Translational Research, The Research Institute at Nationwide Children's, Columbus, OH, United States of America.

ABSTRACT

Purpose: Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI.

Methods: Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice.

Results: Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys.

Conclusions: CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.

No MeSH data available.


Related in: MedlinePlus

Experimental UTI with CONS292 recapitulates the spectrum of pathology observed in spontaneously infected Mgb-/- mice.(A) WT bladder exhibits regenerative apical urothelium and focal mononuclear submucosal infiltrate 14 dpi with CONS292. H&E, 20x objective (B)Mgb-/- bladder exhibits epithelial thickening, and desquamation with luminal crystals and submucosal edema 14 dpi with CONS292. H&E, 20x objective (C) Focal inflammatory cellular infiltrate in the urothelium and perihilar fat (F) was the only evidence of pathological changes in a WT kidney 14 dpi with CONS292. (P, renal papilla). Green dotted line (inset) demarcates the urothelial basement membrane. H&E, 5x objective; inset 20x objective (D)Mgb-/- kidney 14 dpi with CONS292 exhibits widespread changes including areas of dense mixed cellular infiltrate in the interstitium and tubules (inset1) as well as urothelial thickening, suburothelial inflammatory cells, and fibrosis (inset2). Nests of inflammatory cells are found scattered throughout the parenchyma (yellow ovals). Urothelial vacuolization is also present (orange circle, inset2). H&E, 5x objective; inset1 40x objective; inset2 20x objective.
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pone.0139077.g005: Experimental UTI with CONS292 recapitulates the spectrum of pathology observed in spontaneously infected Mgb-/- mice.(A) WT bladder exhibits regenerative apical urothelium and focal mononuclear submucosal infiltrate 14 dpi with CONS292. H&E, 20x objective (B)Mgb-/- bladder exhibits epithelial thickening, and desquamation with luminal crystals and submucosal edema 14 dpi with CONS292. H&E, 20x objective (C) Focal inflammatory cellular infiltrate in the urothelium and perihilar fat (F) was the only evidence of pathological changes in a WT kidney 14 dpi with CONS292. (P, renal papilla). Green dotted line (inset) demarcates the urothelial basement membrane. H&E, 5x objective; inset 20x objective (D)Mgb-/- kidney 14 dpi with CONS292 exhibits widespread changes including areas of dense mixed cellular infiltrate in the interstitium and tubules (inset1) as well as urothelial thickening, suburothelial inflammatory cells, and fibrosis (inset2). Nests of inflammatory cells are found scattered throughout the parenchyma (yellow ovals). Urothelial vacuolization is also present (orange circle, inset2). H&E, 5x objective; inset1 40x objective; inset2 20x objective.

Mentions: Upon histological analysis 14 dpi, CONS-inoculated WT bladders exhibited prominent umbrella cells and a localized inflammatory infiltrate (Fig 5A). In contrast, CONS-infected Mgb-/- bladders demonstrated struvite crystals, urothelial thickening, and submucosal edema (Fig 5B). Inflammation in WT kidneys was absent in the renal parenchyma and restricted to the perihilar fat 14 dpi (Fig 5C). CONS-infected Mgb-/- kidneys manifested widespread interstitial and tubular inflammation with neutrophil-rich leukocyte casts in tubules and a vacuolated urothelium, as observed during spontaneous infection (Fig 5D).


Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse.

Becknell B, Mohamed AZ, Li B, Wilhide ME, Ingraham SE - PLoS ONE (2015)

Experimental UTI with CONS292 recapitulates the spectrum of pathology observed in spontaneously infected Mgb-/- mice.(A) WT bladder exhibits regenerative apical urothelium and focal mononuclear submucosal infiltrate 14 dpi with CONS292. H&E, 20x objective (B)Mgb-/- bladder exhibits epithelial thickening, and desquamation with luminal crystals and submucosal edema 14 dpi with CONS292. H&E, 20x objective (C) Focal inflammatory cellular infiltrate in the urothelium and perihilar fat (F) was the only evidence of pathological changes in a WT kidney 14 dpi with CONS292. (P, renal papilla). Green dotted line (inset) demarcates the urothelial basement membrane. H&E, 5x objective; inset 20x objective (D)Mgb-/- kidney 14 dpi with CONS292 exhibits widespread changes including areas of dense mixed cellular infiltrate in the interstitium and tubules (inset1) as well as urothelial thickening, suburothelial inflammatory cells, and fibrosis (inset2). Nests of inflammatory cells are found scattered throughout the parenchyma (yellow ovals). Urothelial vacuolization is also present (orange circle, inset2). H&E, 5x objective; inset1 40x objective; inset2 20x objective.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581623&req=5

pone.0139077.g005: Experimental UTI with CONS292 recapitulates the spectrum of pathology observed in spontaneously infected Mgb-/- mice.(A) WT bladder exhibits regenerative apical urothelium and focal mononuclear submucosal infiltrate 14 dpi with CONS292. H&E, 20x objective (B)Mgb-/- bladder exhibits epithelial thickening, and desquamation with luminal crystals and submucosal edema 14 dpi with CONS292. H&E, 20x objective (C) Focal inflammatory cellular infiltrate in the urothelium and perihilar fat (F) was the only evidence of pathological changes in a WT kidney 14 dpi with CONS292. (P, renal papilla). Green dotted line (inset) demarcates the urothelial basement membrane. H&E, 5x objective; inset 20x objective (D)Mgb-/- kidney 14 dpi with CONS292 exhibits widespread changes including areas of dense mixed cellular infiltrate in the interstitium and tubules (inset1) as well as urothelial thickening, suburothelial inflammatory cells, and fibrosis (inset2). Nests of inflammatory cells are found scattered throughout the parenchyma (yellow ovals). Urothelial vacuolization is also present (orange circle, inset2). H&E, 5x objective; inset1 40x objective; inset2 20x objective.
Mentions: Upon histological analysis 14 dpi, CONS-inoculated WT bladders exhibited prominent umbrella cells and a localized inflammatory infiltrate (Fig 5A). In contrast, CONS-infected Mgb-/- bladders demonstrated struvite crystals, urothelial thickening, and submucosal edema (Fig 5B). Inflammation in WT kidneys was absent in the renal parenchyma and restricted to the perihilar fat 14 dpi (Fig 5C). CONS-infected Mgb-/- kidneys manifested widespread interstitial and tubular inflammation with neutrophil-rich leukocyte casts in tubules and a vacuolated urothelium, as observed during spontaneous infection (Fig 5D).

Bottom Line: Bladder stones were analyzed by x-ray diffractometry.Bladders and kidneys were subject to histologic analysis.Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Section, Nationwide Children's Hospital, Columbus, OH, United States of America; Department of Pediatrics, Ohio State University School of Medicine, Columbus, OH, United States of America; Center for Clinical and Translational Research, The Research Institute at Nationwide Children's, Columbus, OH, United States of America.

ABSTRACT

Purpose: Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI.

Methods: Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice.

Results: Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys.

Conclusions: CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.

No MeSH data available.


Related in: MedlinePlus