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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

Spontaneous bacterial colonization by CONS in Mgb-/- females versus Mgb+/- and WT controls.Bacteria recovered from urine (CFU/ml), bladders, and kidneys (CFU/organ) were enumerated following serial dilution and culture under non-selective conditions. CONS was identified using standard microbial techniques. p values by Mann-Whitney U test are indicated above the graph. Bacterial burden was significantly higher in Mgb-/- compared to WT (green text) and Mgb+/- (blue text).
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pone.0139077.g002: Spontaneous bacterial colonization by CONS in Mgb-/- females versus Mgb+/- and WT controls.Bacteria recovered from urine (CFU/ml), bladders, and kidneys (CFU/organ) were enumerated following serial dilution and culture under non-selective conditions. CONS was identified using standard microbial techniques. p values by Mann-Whitney U test are indicated above the graph. Bacterial burden was significantly higher in Mgb-/- compared to WT (green text) and Mgb+/- (blue text).

Mentions: By eight weeks of age, urine from 8/19 (42.1%) Mgb-/- females contained > 100,000 colony forming units (cfu) bacteria/ml, identified as CONS in hosts with alkaline urine or a bladder stone. Animals with bladder stones also displayed evidence of lower and upper urinary tract colonization, based on recovery of CONS from bladder and kidney homogenates (Fig 2). Rare positive urine cultures from Mgb-/- females with acidic acid and absence of bladder stones grew Escherichia coli or Enterococcus species. We analyzed a cohort of consecutive Mgb+/- and wild-type (WT) mice from the parental FVB/N strain, to determine if the incidence and magnitude of urinary tract colonization were distinct from Mgb-/- animals. Whereas WT urine was consistently sterile, we detected low levels of spontaneous bacteriuria (1000–8000 cfu/ml) in 3/14 urine samples from Mgb+/- mice. The magnitude of CONS recovered from the urinary tract of Mgb-/- mice was significantly higher than that observed in the Mgb+/- and WT cohorts (Fig 2). We observed no alkaline urine or bladder stones in Mgb+/- or WT mice (Fisher exact test, p = 0.027).


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)

Spontaneous bacterial colonization by CONS in Mgb-/- females versus Mgb+/- and WT controls.Bacteria recovered from urine (CFU/ml), bladders, and kidneys (CFU/organ) were enumerated following serial dilution and culture under non-selective conditions. CONS was identified using standard microbial techniques. p values by Mann-Whitney U test are indicated above the graph. Bacterial burden was significantly higher in Mgb-/- compared to WT (green text) and Mgb+/- (blue text).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139077.g002: Spontaneous bacterial colonization by CONS in Mgb-/- females versus Mgb+/- and WT controls.Bacteria recovered from urine (CFU/ml), bladders, and kidneys (CFU/organ) were enumerated following serial dilution and culture under non-selective conditions. CONS was identified using standard microbial techniques. p values by Mann-Whitney U test are indicated above the graph. Bacterial burden was significantly higher in Mgb-/- compared to WT (green text) and Mgb+/- (blue text).
Mentions: By eight weeks of age, urine from 8/19 (42.1%) Mgb-/- females contained > 100,000 colony forming units (cfu) bacteria/ml, identified as CONS in hosts with alkaline urine or a bladder stone. Animals with bladder stones also displayed evidence of lower and upper urinary tract colonization, based on recovery of CONS from bladder and kidney homogenates (Fig 2). Rare positive urine cultures from Mgb-/- females with acidic acid and absence of bladder stones grew Escherichia coli or Enterococcus species. We analyzed a cohort of consecutive Mgb+/- and wild-type (WT) mice from the parental FVB/N strain, to determine if the incidence and magnitude of urinary tract colonization were distinct from Mgb-/- animals. Whereas WT urine was consistently sterile, we detected low levels of spontaneous bacteriuria (1000–8000 cfu/ml) in 3/14 urine samples from Mgb+/- mice. The magnitude of CONS recovered from the urinary tract of Mgb-/- mice was significantly higher than that observed in the Mgb+/- and WT cohorts (Fig 2). We observed no alkaline urine or bladder stones in Mgb+/- or WT mice (Fisher exact test, p = 0.027).

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