The impact of biological sex on diseases of the urinary tract

Mariano, Lívia Lacerda; Hreha, Teri N.; Hunstad, David A.; Ingersoll, Molly A.

doi:10.1038/s41385-022-00549-0

Cited by 42 publications

(45 citation statements)

References 149 publications

(216 reference statements)

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“…The abundance of ST131 strains in this study may also reflect their relatively recent global proliferation (25), aided by this an ability to efficiently colonize and persist in human intestinal reservoirs (51)(52)(53)(54), which is regarded as the source of most urinary Enterobacterales (55)(56)(57). While ST131 intestinal colonization exhibits no sex differences (58)(59)(60), CAUTI patients in this study were disproportionately male, possibly reflecting the enhanced E. coli infection severity in males observed in an animal model of direct bladder inoculation (61,62). It is unclear whether the association between ST131 strains and CAUTI arises from increased pathogenic potential of these strains, an association with male patients, or a combination thereof.…”

Section: Discussionmentioning

confidence: 73%

“…While ST131 intestinal colonization exhibits no sex differences ( 58 – 60 ), CAUTI patients in this study were disproportionately male, possibly reflecting the enhanced E . coli infection severity in males observed in an animal model of direct bladder inoculation ( 61 , 62 ). It is unclear whether the association between ST131 strains and CAUTI arises from increased pathogenic potential of these strains, an association with male patients, or a combination thereof.…”

Section: Discussionmentioning

confidence: 99%

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E. coli catheter-associated urinary tract infections are associated with distinctive virulence and biofilm gene determinants

Zou¹,

Potter²,

Th³

et al. 2023

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Urinary catheterization facilitates urinary tract colonization by Escherichia coli and increases infection risk. Here we aimed to identify strain-specific characteristics associated with the transition from colonization to infection in catheterized patients. In a single-site study population, we compared E. coli isolates from patients with catheter-associated asymptomatic bacteriuria (CAASB) to those with catheter-associated urinary tract infection (CAUTI). CAUTI isolates were dominated by a phylotype B2 subclade containing the multidrug resistant ST131 lineage relative to CAASB isolates, which were phylogenetically more diverse. A distinctive combination of fvirulence-associated genes was present in the CAUTI-associated B2 subclade. Catheterassociated biofilm formation was widespread among isolates and did not distinguish CAUTI from CAASB strains. Preincubation with CAASB strains could potently inhibit catheter colonization by multiple ST131 CAUTI isolates. Comparative genomic analysis identified a group of variable genes associated with high catheter-biofilm formation present in both CAUTI and CAASB strains. Among these, ferric citrate transport (Fec) system genes were experimentally associated with enhanced catheter biofilm formation using reporter and fecA deletion strains. Together, these results are consistent with a variable role for catheter biofilm formation in promoting CAUTI by ST131-like strains or resisting CAUTI by lower risk strains that engage in niche exclusion.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

E. coli catheter-associated urinary tract infections are associated with distinctive virulence and biofilm gene determinants

Zou¹,

Potter²,

Th³

et al. 2023

JCI Insight

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“…To address potential reverse causation, we performed a lagged analysis of the exposure for 2 years, which could strengthen the temporality and allow a time window for bladder cancer development. To control for confounding factors, our multi-adjusted models adjusted for several covariates associated with bladder cancer risk ( 25 – 34 ). We first stratified the analyses jointly by age, gender, and UK Biobank assessment center to estimate the crude associations of MetS and its components with subsequent bladder cancer risk.…”

Section: Methodsmentioning

confidence: 99%

Association of metabolic syndrome and the risk of bladder cancer: A prospective cohort study

et al. 2022

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BackgroundMetabolic syndrome (MetS) and its components have been shown as risk factors for several solid cancers. However, current epidemiological evidence about the relevance of MetS and bladder cancer risk was limited.MethodsWe conducted a prospective cohort study of 476,986 participants with undiagnosed bladder cancer based on the UK Biobank. MetS was defined as the presence of at least three of the five selected indicators: hypertension, central obesity, raised triglyceride, reduced HDL-cholesterol, and raised fasting plasma glucose. Bladder cancer has been identified through contact with the British Cancer Registry (median follow-up time: 6.6 years). We assessed hazard ratio (HR) and 95% confidence interval (CI) through Cox proportional hazard regression after adjusting for demographic and lifestyle factors. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method.ResultsDuring a follow-up of 3,112,566 person-years, 487 cases of bladder cancer were ascertained. MetS (HR = 1.32, 95% CI = 1.08–1.61), central obesity (HR = 1.39, 95% CI = 1.15–1.68), dyslipidemia for HDL cholesterol (HR = 1.31, 95% CI = 1.04–1.66), and hyperglycemia (HR = 1.44, 95% CI = 1.16–1.79) were associated with elevated risk of bladder cancer. Bladder cancer risk increased with the number of MetS components. In stratified analyses, MetS showed similar effects in bladder cancer independently with sex, age, cigarette and alcohol use, physical activity, and dietary factors. Higher waist circumference, BMI, fasting blood glucose, and glycosylated hemoglobin were independently associated with increased risk of bladder cancer, with no evidence against non-linearity.ConclusionMetS might be an independent risk factor for bladder cancer. Our findings highlighted the importance of individualized management of MetS components for preventing bladder cancer.

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“…Urinary tract infection (UTI), caused predominantly by uropathogenic Escherichia coli (UPEC), is one of the most prevalent human bacterial infections (1). Women experience UTI at a significantly higher rate than men, and children, the elderly, pregnant women, and immunocompromised individuals are at greater risk than the general population for complications such as chronic infection, pyelonephritis, and kidney damage (2)(3)(4)(5)(6)(7). About one in two women will have a UTI in her lifetime, with the highest risk between the ages of 16 and 35, when women are 35 times more likely than men to have a UTI (8).…”

Section: Introductionmentioning

confidence: 99%

Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection

et al. 2023

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Urinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early in infection, by reducing the inoculum or with antibiotics after infection, completely abrogated the protective memory response. We observed a mixed T helper (T H ) cell polarization, composed of T H 1, T H 2, and T H 17 T cells, among T cells infiltrating the bladder during primary infection. Thus, we hypothesized that reducing antigen load altered T H cell polarization, leading to poor memory. Unexpectedly, however, T H cell polarization was unchanged in these scenarios. Instead, we uncovered a population of tissue-resident memory (T RM ) T cells that was significantly reduced in the absence of sufficient antigen. Demonstrating that T RM cells are necessary for immune memory, transfer of lymph node– or spleen-derived infection-experienced T cells to naïve animals did not confer protection against infection. Supporting that T RM cells are sufficient to protect against recurrent UTI, animals depleted of systemic T cells, or treated with FTY720 to block memory lymphocyte migration from lymph nodes to infected tissue, were equally protected compared with unmanipulated mice against a second UTI. Thus, we uncovered an unappreciated key role for T RM cells in the memory response to bacterial infection in the bladder mucosa, providing a target for non–antibiotic-based immunotherapy and/or new vaccine strategies to prevent recurrent UTI.

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The impact of biological sex on diseases of the urinary tract

Cited by 42 publications

References 149 publications

E. coli catheter-associated urinary tract infections are associated with distinctive virulence and biofilm gene determinants

E. coli catheter-associated urinary tract infections are associated with distinctive virulence and biofilm gene determinants

Association of metabolic syndrome and the risk of bladder cancer: A prospective cohort study

Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection

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