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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: CONS was cultured as a solitary isolate from Mgb-/- bladder stones.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.

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

Mgb-/- female mice exhibit struvite urolithiasis associated with spontaneous UTI.Ultrasound of Mgb-/- female mice demonstrates bladder (A) and kidney (B) echogenic foci representing stones (circled) with acoustic shadowing (arrows). (C) Bladder stones (ST) harvested from a Mgb-/- female bladder (BL) with a spontaneous UTI. Stone analysis confirmed struvite (magnesium ammonium phosphate) as the major chemical component. (D) Urine from Mgb-/- females with bladder stones or UTI is alkaline compared to Mgb-/- females with sterile urine or lacking stones. p values by Mann-Whitney U test are indicated above the graph. (E) Gram stain of urine sediment from Mgb-/- females with struvite bladder stones demonstrates Gram-positive cocci in clusters consistent with Staphylococcal species. 100x objective. (F) Bright field light micrograph of urine sediment from Mgb-/- females with struvite bladder stones demonstrates typical “coffin-lid” appearance of struvite crystals. (G) Wright-Giemsa stain showing struvite crystals (black arrow), mononuclear and polymorphonuclear leukocytes (black and white arrowheads, respectively), and desquamated urothelial cells (white arrow) in urine sediment from an Mgb-/- female with spontaneous bacteriuria. 100x objective.
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pone.0139077.g001: Mgb-/- female mice exhibit struvite urolithiasis associated with spontaneous UTI.Ultrasound of Mgb-/- female mice demonstrates bladder (A) and kidney (B) echogenic foci representing stones (circled) with acoustic shadowing (arrows). (C) Bladder stones (ST) harvested from a Mgb-/- female bladder (BL) with a spontaneous UTI. Stone analysis confirmed struvite (magnesium ammonium phosphate) as the major chemical component. (D) Urine from Mgb-/- females with bladder stones or UTI is alkaline compared to Mgb-/- females with sterile urine or lacking stones. p values by Mann-Whitney U test are indicated above the graph. (E) Gram stain of urine sediment from Mgb-/- females with struvite bladder stones demonstrates Gram-positive cocci in clusters consistent with Staphylococcal species. 100x objective. (F) Bright field light micrograph of urine sediment from Mgb-/- females with struvite bladder stones demonstrates typical “coffin-lid” appearance of struvite crystals. (G) Wright-Giemsa stain showing struvite crystals (black arrow), mononuclear and polymorphonuclear leukocytes (black and white arrowheads, respectively), and desquamated urothelial cells (white arrow) in urine sediment from an Mgb-/- female with spontaneous bacteriuria. 100x objective.

Mentions: To investigate the incidence and etiology of bladder stones in Mgb-/- females, we performed serial ultrasounds and urine cultures in a cohort of 19 consecutive 4 week old Mgb-/- female mice. If stones were absent and urine remained sterile, we repeated ultrasound and cultures at 6 and 8 weeks of age. At 8 weeks, all animals were euthanized and tissues were collected for culture and histopathology. We identified bladder stones in 6/19 Mgb-/- mice (31.6%; Fig 1A). In two instances, we observed concurrent kidney and bladder stones (Fig 1B). At necropsy, we enucleated multiple stones from dissected Mgb-/- bladders (Fig 1C). All bladder stones were composed of ≥ 90% struvite with up to 10% apatite, consistent with an infectious origin.


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)

Mgb-/- female mice exhibit struvite urolithiasis associated with spontaneous UTI.Ultrasound of Mgb-/- female mice demonstrates bladder (A) and kidney (B) echogenic foci representing stones (circled) with acoustic shadowing (arrows). (C) Bladder stones (ST) harvested from a Mgb-/- female bladder (BL) with a spontaneous UTI. Stone analysis confirmed struvite (magnesium ammonium phosphate) as the major chemical component. (D) Urine from Mgb-/- females with bladder stones or UTI is alkaline compared to Mgb-/- females with sterile urine or lacking stones. p values by Mann-Whitney U test are indicated above the graph. (E) Gram stain of urine sediment from Mgb-/- females with struvite bladder stones demonstrates Gram-positive cocci in clusters consistent with Staphylococcal species. 100x objective. (F) Bright field light micrograph of urine sediment from Mgb-/- females with struvite bladder stones demonstrates typical “coffin-lid” appearance of struvite crystals. (G) Wright-Giemsa stain showing struvite crystals (black arrow), mononuclear and polymorphonuclear leukocytes (black and white arrowheads, respectively), and desquamated urothelial cells (white arrow) in urine sediment from an Mgb-/- female with spontaneous bacteriuria. 100x objective.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139077.g001: Mgb-/- female mice exhibit struvite urolithiasis associated with spontaneous UTI.Ultrasound of Mgb-/- female mice demonstrates bladder (A) and kidney (B) echogenic foci representing stones (circled) with acoustic shadowing (arrows). (C) Bladder stones (ST) harvested from a Mgb-/- female bladder (BL) with a spontaneous UTI. Stone analysis confirmed struvite (magnesium ammonium phosphate) as the major chemical component. (D) Urine from Mgb-/- females with bladder stones or UTI is alkaline compared to Mgb-/- females with sterile urine or lacking stones. p values by Mann-Whitney U test are indicated above the graph. (E) Gram stain of urine sediment from Mgb-/- females with struvite bladder stones demonstrates Gram-positive cocci in clusters consistent with Staphylococcal species. 100x objective. (F) Bright field light micrograph of urine sediment from Mgb-/- females with struvite bladder stones demonstrates typical “coffin-lid” appearance of struvite crystals. (G) Wright-Giemsa stain showing struvite crystals (black arrow), mononuclear and polymorphonuclear leukocytes (black and white arrowheads, respectively), and desquamated urothelial cells (white arrow) in urine sediment from an Mgb-/- female with spontaneous bacteriuria. 100x objective.
Mentions: To investigate the incidence and etiology of bladder stones in Mgb-/- females, we performed serial ultrasounds and urine cultures in a cohort of 19 consecutive 4 week old Mgb-/- female mice. If stones were absent and urine remained sterile, we repeated ultrasound and cultures at 6 and 8 weeks of age. At 8 weeks, all animals were euthanized and tissues were collected for culture and histopathology. We identified bladder stones in 6/19 Mgb-/- mice (31.6%; Fig 1A). In two instances, we observed concurrent kidney and bladder stones (Fig 1B). At necropsy, we enucleated multiple stones from dissected Mgb-/- bladders (Fig 1C). All bladder stones were composed of ≥ 90% struvite with up to 10% apatite, consistent with an infectious origin.

Bottom Line: CONS was cultured as a solitary isolate from Mgb-/- bladder stones.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.

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