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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

Urinary diversion decreases CONS292 susceptibility in Mgb-/- mice.Mgb-/- females post-CV (Mgb-/- CV) were transurethrally challenged with 108 CFU of CONS292, along with undiverted Mgb-/- and WT mice. Bacteria were recovered 14 dpi from urine, bladder, and kidneys, then enumerated. p values by Mann-Whitney U test are indicated above the graph. A significantly higher magnitude of bacterial burden was observed in urine and all organs from undiverted Mgb-/- versus WT mice (green text) and versus Mgb-/- mice with CV (black text).
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pone.0139077.g006: Urinary diversion decreases CONS292 susceptibility in Mgb-/- mice.Mgb-/- females post-CV (Mgb-/- CV) were transurethrally challenged with 108 CFU of CONS292, along with undiverted Mgb-/- and WT mice. Bacteria were recovered 14 dpi from urine, bladder, and kidneys, then enumerated. p values by Mann-Whitney U test are indicated above the graph. A significantly higher magnitude of bacterial burden was observed in urine and all organs from undiverted Mgb-/- versus WT mice (green text) and versus Mgb-/- mice with CV (black text).

Mentions: We hypothesized that the heightened susceptibility of the Mgb-/- urinary tract to CONS can be attributed at least in part to urine stasis. We therefore performed CV using absorbable polydioxanone suture in a cohort of uninfected Mgb-/- females, and confirmed the absence of urolithiasis, acidic pH, and sterility of the urine immediately prior to inoculation with 108 CFU CONS292.[6,9,10] Following a 14 day period of observation, animals were euthanized and CONS extracted from urinary tracts to determine bacterial burden. As expected from our previous results, we recovered significantly more CONS from undiverted Mgb-/- than WT urine, bladders, and kidneys (Fig 6). WT bladders and kidneys consistently showed reduced bacterial burden relative to undiverted Mgb-/-, with 37.5% of WT organs demonstrating complete clearance of CONS compared to 0% in undiverted Mgb-/- mice. We also recovered significantly fewer CONS from urine, bladder, and kidneys of diverted Mgb-/- than from undiverted Mgb-/- animals. In the kidneys, bacterial burden was comparable between Mgb-/- with CV and WT (p = 0.79 [right kidney] and p = 0.88 [left kidney]). However, bladder (p = 0.0009) and urine (p = 0.02) CONS levels remained increased in Mgb-/- versus WT regardless of CV status (Fig 6).


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)

Urinary diversion decreases CONS292 susceptibility in Mgb-/- mice.Mgb-/- females post-CV (Mgb-/- CV) were transurethrally challenged with 108 CFU of CONS292, along with undiverted Mgb-/- and WT mice. Bacteria were recovered 14 dpi from urine, bladder, and kidneys, then enumerated. p values by Mann-Whitney U test are indicated above the graph. A significantly higher magnitude of bacterial burden was observed in urine and all organs from undiverted Mgb-/- versus WT mice (green text) and versus Mgb-/- mice with CV (black text).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139077.g006: Urinary diversion decreases CONS292 susceptibility in Mgb-/- mice.Mgb-/- females post-CV (Mgb-/- CV) were transurethrally challenged with 108 CFU of CONS292, along with undiverted Mgb-/- and WT mice. Bacteria were recovered 14 dpi from urine, bladder, and kidneys, then enumerated. p values by Mann-Whitney U test are indicated above the graph. A significantly higher magnitude of bacterial burden was observed in urine and all organs from undiverted Mgb-/- versus WT mice (green text) and versus Mgb-/- mice with CV (black text).
Mentions: We hypothesized that the heightened susceptibility of the Mgb-/- urinary tract to CONS can be attributed at least in part to urine stasis. We therefore performed CV using absorbable polydioxanone suture in a cohort of uninfected Mgb-/- females, and confirmed the absence of urolithiasis, acidic pH, and sterility of the urine immediately prior to inoculation with 108 CFU CONS292.[6,9,10] Following a 14 day period of observation, animals were euthanized and CONS extracted from urinary tracts to determine bacterial burden. As expected from our previous results, we recovered significantly more CONS from undiverted Mgb-/- than WT urine, bladders, and kidneys (Fig 6). WT bladders and kidneys consistently showed reduced bacterial burden relative to undiverted Mgb-/-, with 37.5% of WT organs demonstrating complete clearance of CONS compared to 0% in undiverted Mgb-/- mice. We also recovered significantly fewer CONS from urine, bladder, and kidneys of diverted Mgb-/- than from undiverted Mgb-/- animals. In the kidneys, bacterial burden was comparable between Mgb-/- with CV and WT (p = 0.79 [right kidney] and p = 0.88 [left kidney]). However, bladder (p = 0.0009) and urine (p = 0.02) CONS levels remained increased in Mgb-/- versus WT regardless of CV status (Fig 6).

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