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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

Mgb-/- mice develop persistent bacteriuria and alkaline pH following transurethral challenge with CONS292.(A) Mgb-/- mice exhibit increased magnitude of CONS292 recovery from urine and bladder than WT controls 1 dpi, but renal colonization is comparable. p values by Mann-Whitney U test are indicated above the graph. (B) Mgb-/- mice develop persistent bacteriuria, whereas WT control clear CONS292 from urine by 10 dpi. p values by Mann-Whitney U test are indicated above the graph. (C) Gram-positive cocci in clusters from Mgb-/- urine 14 dpi with 108 CFU of CONS292. 100x objective. (D) Mgb-/- urine is uniquely alkaline compared to WT urine 10 dpi with CONS292. p value by Mann-Whitney U test is indicated above the graph. Similar results were obtained 3 dpi with p = 0.0001 (Data not shown). (E) Echogenic debris in a Mgb-/- bladder 14 dpi CONS292, confirmed as bladder stones at necropsy.
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pone.0139077.g004: Mgb-/- mice develop persistent bacteriuria and alkaline pH following transurethral challenge with CONS292.(A) Mgb-/- mice exhibit increased magnitude of CONS292 recovery from urine and bladder than WT controls 1 dpi, but renal colonization is comparable. p values by Mann-Whitney U test are indicated above the graph. (B) Mgb-/- mice develop persistent bacteriuria, whereas WT control clear CONS292 from urine by 10 dpi. p values by Mann-Whitney U test are indicated above the graph. (C) Gram-positive cocci in clusters from Mgb-/- urine 14 dpi with 108 CFU of CONS292. 100x objective. (D) Mgb-/- urine is uniquely alkaline compared to WT urine 10 dpi with CONS292. p value by Mann-Whitney U test is indicated above the graph. Similar results were obtained 3 dpi with p = 0.0001 (Data not shown). (E) Echogenic debris in a Mgb-/- bladder 14 dpi CONS292, confirmed as bladder stones at necropsy.

Mentions: CONS292 initially colonized the urinary tracts of both Mgb-/- and WT mice (Fig 4A). However, we observed significantly less CONS burden in WT urine and bladders 1 day post infection (dpi), whereas renal colonization was comparable between genotypes (Fig 4A). CONS bacteriuria persisted for at least 2 weeks in Mgb-/- mice, whereas wild-type urine was sterile by 10 days post infection (dpi; Fig 4B). Mgb-/- urine uniquely contained Gram-positive cocci in clusters 14 dpi (Fig 4C). Mgb-/- urine pH was significantly more alkaline than WT urine as early as 3 dpi (p = 0.0001, data not shown) and at 10 dpi (p = 0.0002, Fig 4D). Mgb-/- mice infected with CONS292 demonstrated struvite crystalluria and bladder stones 14 dpi, whereas WT mice did not (Fig 4E).


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-/- mice develop persistent bacteriuria and alkaline pH following transurethral challenge with CONS292.(A) Mgb-/- mice exhibit increased magnitude of CONS292 recovery from urine and bladder than WT controls 1 dpi, but renal colonization is comparable. p values by Mann-Whitney U test are indicated above the graph. (B) Mgb-/- mice develop persistent bacteriuria, whereas WT control clear CONS292 from urine by 10 dpi. p values by Mann-Whitney U test are indicated above the graph. (C) Gram-positive cocci in clusters from Mgb-/- urine 14 dpi with 108 CFU of CONS292. 100x objective. (D) Mgb-/- urine is uniquely alkaline compared to WT urine 10 dpi with CONS292. p value by Mann-Whitney U test is indicated above the graph. Similar results were obtained 3 dpi with p = 0.0001 (Data not shown). (E) Echogenic debris in a Mgb-/- bladder 14 dpi CONS292, confirmed as bladder stones at necropsy.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139077.g004: Mgb-/- mice develop persistent bacteriuria and alkaline pH following transurethral challenge with CONS292.(A) Mgb-/- mice exhibit increased magnitude of CONS292 recovery from urine and bladder than WT controls 1 dpi, but renal colonization is comparable. p values by Mann-Whitney U test are indicated above the graph. (B) Mgb-/- mice develop persistent bacteriuria, whereas WT control clear CONS292 from urine by 10 dpi. p values by Mann-Whitney U test are indicated above the graph. (C) Gram-positive cocci in clusters from Mgb-/- urine 14 dpi with 108 CFU of CONS292. 100x objective. (D) Mgb-/- urine is uniquely alkaline compared to WT urine 10 dpi with CONS292. p value by Mann-Whitney U test is indicated above the graph. Similar results were obtained 3 dpi with p = 0.0001 (Data not shown). (E) Echogenic debris in a Mgb-/- bladder 14 dpi CONS292, confirmed as bladder stones at necropsy.
Mentions: CONS292 initially colonized the urinary tracts of both Mgb-/- and WT mice (Fig 4A). However, we observed significantly less CONS burden in WT urine and bladders 1 day post infection (dpi), whereas renal colonization was comparable between genotypes (Fig 4A). CONS bacteriuria persisted for at least 2 weeks in Mgb-/- mice, whereas wild-type urine was sterile by 10 days post infection (dpi; Fig 4B). Mgb-/- urine uniquely contained Gram-positive cocci in clusters 14 dpi (Fig 4C). Mgb-/- urine pH was significantly more alkaline than WT urine as early as 3 dpi (p = 0.0001, data not shown) and at 10 dpi (p = 0.0002, Fig 4D). Mgb-/- mice infected with CONS292 demonstrated struvite crystalluria and bladder stones 14 dpi, whereas WT mice did not (Fig 4E).

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