Innate Immune Responses to Bladder Infection

Hayes, Byron W.; Abraham, Soman N.

doi:10.1128/microbiolspec.uti-0024-2016

Cited by 40 publications

(22 citation statements)

References 57 publications

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“…Some of the elevated cytokines, such as IL-10, are anti-inflammatory (63), suggesting there are switches between pro- and anti-inflammatory responses as the infection progresses. This is consistent with changes in innate immune responses observed for other uropathogens, including UPEC and Group B streptococcus (60, 62, 64). TNF-α and IL-6 are also elevated in bladder homogenates from mice at 48 hpi (Peng 2016—it’s currently ref 308).…”

Section: Host Interactionssupporting

confidence: 87%

“…Although innate immune responses to UTI are an active area of investigation, most of these studies have focused on uropathogenic E. coli (60–62). Because there are several key differences between P. mirabilis UTI and UPEC UTI, including urolithiasis, bacterial metabolism during UTI, and intracellular vs. luminal niches in the bladder, we will focus sharply here on studies that specifically examine P. mirabilis .…”

Section: Host Interactionsmentioning

confidence: 99%

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Pathogenesis of Proteus mirabilis Infection

2018

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Proteus mirabilis, a Gram-negative rod-shaped bacterium most noted for its swarming motility and urease activity, frequently causes catheter-associated urinary tract infections (CAUTI) that are often polymicrobial. These infections may be accompanied by urolithiasis, development of bladder or kidney stones due to alkalinization of urine from urease-catalyzed urea hydrolysis. Adherence of the bacterium to epithelial and catheter surfaces is mediated by 17 different fimbriae, most notably MR/P fimbriae. Repressors of motility are often encoded by these fimbrial operons. Motility is mediated by flagella encoded on a single contiguous 54 kb chromosomal sequence. On agar plates, P. mirabilis undergoes a morphological conversion to a filamentous swarmer cell expressing hundreds of flagella. When swarms from different strains meet, a line of demarcation, a “Dienes line”, develops due to the killing action of each strain’s type VI secretion system. During infection, histological damage is caused by cytotoxins including hemolysin and a variety of proteases, some autotransported. The pathogenesis of infection, including assessment of individual genes or global screens for virulence or fitness factors has been assessed in murine models of ascending UTI or CAUTI using both single-species and polymicrobial models. Global gene expression studies carried out in culture and in the murine model have revealed the unique metabolism of this bacterium. Vaccines, using MR/P fimbria and its adhesin, MrpH, have been shown to be efficacious in the murine model. A comprehensive review of factors associated with urinary tract infection is presented, encompassing both historical perspectives and current advances.

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Section: Host Interactionssupporting

confidence: 87%

Section: Host Interactionsmentioning

confidence: 99%

Pathogenesis of Proteus mirabilis Infection

2018

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“…This indicates that pretreatment with L. mutabilis specifically targets RNase 7 to fend off bacteria adhering to the uroepithelial cell surface. Interestingly, RNase 7 is naturally expressed in uroepithelial cells and is known to have bactericidal effect on Gram-negative and Gram-positive bacteria as well as MDR strains [24–26], which is in line with our results. Decreased bacterial adhesion with L. mutabilis pretreatment as well as upregulation of RNase 7 expression was seen both in normal and hyperglycemic conditions, mimicking metabolic conditions in the urinary bladder of diabetic patients.…”

Section: Discussionsupporting

confidence: 92%

Lupinus mutabilis Edible Beans Protect against Bacterial Infection in Uroepithelial Cells

Kamolvit

Nilsén

Zambrana

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Lupinus mutabilis is a South American herb with edible beans, known to reduce serum glucose levels in diabetic patients. Furthermore, L. mutabilis contains phytochemicals known to decrease bacterial load. Based on the increased urinary tract infections experienced among patients with diabetes, we investigated the effect of L. mutabilis on bladder epithelial cells in the protection of E. coli infection during normal and high glucose concentrations. We did not observe any direct antibacterial effect by L. mutabilis extract. Instead we observed an influence on the host cells, with indirect impact on bacteria and their possibility of causing infection. L. mutabilis extract decreased adhesion to bladder epithelial cells of uropathogenic bacteria, including drug-resistant strains. Moreover, uroplakin1a, involved in adhesion, was downregulated while the antimicrobial peptide RNase 7 was upregulated in L. mutabilis treated cells irrespectively of glucose concentration. This supports an early effect fighting bacteria. Additionally, L. mutabilis prevented bacterial biofilm formation, which is used by bacteria to evade the immune system and antibiotics. In summary, L. mutabilis protects against bacterial infection in uroepithelial cells by preventing adhesion through alteration of the cell surface, increasing antimicrobial peptide expression, and reducing biofilm formation. Together, this promotes bacterial clearance, suggesting that L. mutabilis as extract or as a dietary item can contribute to the prevention of urinary tract infections, which is of importance in an era of increasing antibiotic resistance.

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“…Thus, urinary supernatant may be a poor substrate for recovering sequestered organisms. However, it is also known that an innate immune response to UTI exacerbates the shedding of urothelial cells into urine ( 15 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

Reassessment of Routine Midstream Culture in Diagnosis of Urinary Tract Infection

et al. 2019

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Midstream urine (MSU) culture remains the gold standard diagnostic test for confirming urinary tract infection (UTI). We previously showed that patients with chronic lower urinary tract symptoms (LUTS) below the diagnostic cutoff on MSU culture may still harbor bacterial infection and that their antibiotic treatment was associated with symptom resolution. Here, we evaluated the results of the United Kingdom’s MSU culture in symptomatic patients and controls. Next, we compared the bacterial enrichment capabilities of the MSU culture with those of a 50-µl uncentrifuged culture, a 30-ml centrifuged sediment culture, and 16S rRNA gene sequencing. This study was conducted on urine specimens from 33 LUTS patients attending their first clinical appointment (mean age, 48.7 years; standard deviation [SD], 16.5 years), 30 LUTS patients on treatment (mean age, 47.8 years; SD, 16.5 years) whose symptoms had relapsed, and 29 asymptomatic controls (mean age, 40.7 years, SD, 15.7 years). We showed that the routine MSU culture, adopting the UK interpretation criteria tailored to acute UTI, failed to detect a variety of bacterial species, including recognized uropathogens. Moreover, the diagnostic MSU culture was unable to discriminate between patients and controls. In contrast, genomic analysis of urine enriched by centrifugation discriminated between the groups, generating a more accurate understanding of species richness. In conclusion, the United Kingdom’s MSU protocol misses a significant proportion of bacteria, which include recognized uropathogens, and may be unsuitable for excluding UTI in patients with LUTS.

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Innate Immune Responses to Bladder Infection

Cited by 40 publications

References 57 publications

Pathogenesis of Proteus mirabilis Infection

Pathogenesis of Proteus mirabilis Infection

Lupinus mutabilis Edible Beans Protect against Bacterial Infection in Uroepithelial Cells

Reassessment of Routine Midstream Culture in Diagnosis of Urinary Tract Infection

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