Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence

Islam, Md. Jahirul; Bagale, Kamal; John, Preeti P; Kurtz, Zachary

doi:10.1128/msphere.00004-22

Cited by 10 publications

(4 citation statements)

References 57 publications

(80 reference statements)

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“…The ability of bacteria to respond to this hormone may have a role in the propagation of infection. Previous investigations have shown significantly elevated urinary NE in diabetic patients with and without UTIs [29,30]. In our study we found that NE and glucose both activated the metabolism of the most frequent uropathogens, such as E. coli, Ps.…”

Section: Discussionsupporting

confidence: 68%

“…pneumoniae is one of the most common causative organisms of UTIs [28]. Hyperglycemia is frequent in acute patients due to the increased release of stress hormones such as catecholamines and cortisol, but can also result from the cascade effect of proinflammatory cytokines in emergencies such as acute coronary syndrome, pulmonary edema, pulmonary embolism, injuries, severe infections and sepsis [27][28][29][30]. Thus, all these conditions may result in raised levels of NE and glucose in urine and lead to chronic UTIs caused by Klebsiella spp.…”

Section: Discussionmentioning

confidence: 99%

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Effect of pH, Norepinephrine and Glucose on Metabolic and Biofilm Activity of Uropathogenic Microorganisms

et al. 2023

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Urinary tract infection (UTIs) aremainly caused by a number of anatomical and physiological dysfunctions, but there are also some iatrogenic factors, including the use of certain medications, that contribute to the development of UTIs. The virulence of bacteria that colonize the urinary tract may be modified by pH and by the presence of soluble substances in urine, such as norepinephrine (NE) and glucose. In this work, we studied the influence of NE and glucose across a range of pHs (5, 7, 8) on the biomass, matrix production and metabolism of uropathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis. We used Congo red and gentian violet to stain the extracellular matrix and biomass, respectively, of biofilms. The optical density of staining of the biofilms was measured using a multichannel spectrophotometer. The metabolic activity was analyzed by MTT assay. It was shown that NE and glucose stimulate biomass production both in the Gram-negative and Gram-positive uropathogens. The metabolic activity in the presence of glucose was higher at pH 5 for E. coli (in 4.0 ± 0.1 times), Ps. aeruginosa (in 8.2 ± 0.2 times) and Kl. pneumoniae (in 4.1 ± 0.2 times). Matrix production of Kl. pneumoniae increased under NE (in 8.2 ± 0.2 times) and in the presence of glucose (in 1.5 ± 0.3 times). Thus, NE and glucose in urine may lead to persistent UTI under patient stress and in the case of metabolic glucose disorders.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Effect of pH, Norepinephrine and Glucose on Metabolic and Biofilm Activity of Uropathogenic Microorganisms

et al. 2023

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“…It is therefore not surprising that UPEC would rely heavily upon oligo-, dipeptide, and amino acid transporters during UTI ( 15 , 16 ). An exception to this may be during glycosuria in which UPEC shifts toward glycolytic metabolism; however, even in this condition, UPEC was found reliant on the methionine ABC uptake system ( metQN ) ( 57 ). This supports the necessity of ABC importers among a wide variety of infectious niches including rapid growth in planktonic populations, intracellular survival, and diabetic urine.…”

Section: Discussionmentioning

confidence: 99%

Emerging roles for ABC transporters as virulence factors in uropathogenic Escherichia coli

Shea,

Forsyth,

Stocki

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Urinary tract infections (UTI) account for a substantial financial burden globally. Over 75% of UTIs are caused by uropathogenic Escherichia coli (UPEC), which have demonstrated an extraordinarily rapid growth rate in vivo. This rapid growth rate appears paradoxical given that urine and the human urinary tract are relatively nutrient-restricted. Thus, we lack a fundamental understanding of how uropathogens propel growth in the host to fuel pathogenesis. Here, we used large in silico, in vivo, and in vitro screens to better understand the role of UPEC transport mechanisms and their contributions to uropathogenesis. In silico analysis of annotated transport systems indicated that the ATP-binding cassette (ABC) family of transporters was most conserved among uropathogenic bacterial species, suggesting their importance. Consistent with in silico predictions, we determined that the ABC family contributed significantly to fitness and virulence in the urinary tract: these were overrepresented as fitness factors in vivo (37.2%), liquid media (52.3%), and organ agar (66.2%). We characterized 12 transport systems that were most frequently defective in screening experiments by generating in-frame deletions. These mutant constructs were tested in urovirulence phenotypic assays and produced differences in motility and growth rate. However, deletion of multiple transport systems was required to achieve substantial fitness defects in the cochallenge murine model. This is likely due to genetic compensation among transport systems, highlighting the centrality of ABC transporters in these organisms. Therefore, these nutrient uptake systems play a concerted, critical role in pathogenesis and are broadly applicable candidate targets for therapeutic intervention.

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“…Research showed that glycosuria exposure augmented group B Streptococcus epithelial adherence and hemolysis and antimicrobial peptide resistance ( John et al., 2021 ). Islam found that glycosuria rapidly increased gene expression encoding biofilm formation and central metabolic virulence of uropathogenic E. coli ( Islam et al., 2022 ). Whether urine glucose plays a greater role in identifying uropathogenic bacteria from colonizers needs more data to be supported.…”

Section: Discussionmentioning

confidence: 99%

Building a nomogram plot based on the nanopore targeted sequencing for predicting urinary tract pathogens and differentiating from colonizing bacteria

Jiang

Wei

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundThe identification of uropathogens (UPBs) and urinary tract colonizing bacteria (UCB) conduces to guide the antimicrobial therapy to reduce resistant bacterial strains and study urinary microbiota. This study established a nomogram based on the nanopore-targeted sequencing (NTS) and other infectious risk factors to distinguish UPB from UCB.MethodsBasic information, medical history, and multiple urine test results were continuously collected and analyzed by least absolute shrinkage and selection operator (LASSO) regression, and multivariate logistic regression was used to determine the independent predictors and construct nomogram. Receiver operating characteristics, area under the curve, decision curve analysis, and calibration curves were used to evaluate the performance of the nomogram.ResultsIn this study, the UPB detected by NTS accounted for 74.1% (401/541) of all urinary tract microorganisms. The distribution of ln(reads) between UPB and UCB groups showed significant difference (OR = 1.39; 95% CI, 1.246–1.551, p < 0.001); the reads number in NTS reports could be used for the preliminary determination of UPB (AUC=0.668) with corresponding cutoff values being 7.042. Regression analysis was performed to determine independent predictors and construct a nomogram, with variables ranked by importance as ln(reads) and the number of microbial species in the urinary tract of NTS, urine culture, age, urological neoplasms, nitrite, and glycosuria. The calibration curve showed an agreement between the predicted and observed probabilities of the nomogram. The decision curve analysis represented that the nomogram would benefit clinical interventions. The performance of nomogram with ln(reads) (AUC = 0.767; 95% CI, 0.726–0.807) was significantly better (Z = 2.304, p-value = 0.021) than that without ln(reads) (AUC = 0.727; 95% CI, 0.681–0.772). The rate of UPB identification of nomogram was significantly higher than that of ln(reads) only (χ2 = 7.36, p-value = 0.009).ConclusionsNTS is conducive to distinguish uropathogens from colonizing bacteria, and the nomogram based on NTS and multiple independent predictors has better prediction performance of uropathogens.

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Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence

Cited by 10 publications

References 57 publications

Effect of pH, Norepinephrine and Glucose on Metabolic and Biofilm Activity of Uropathogenic Microorganisms

Effect of pH, Norepinephrine and Glucose on Metabolic and Biofilm Activity of Uropathogenic Microorganisms

Emerging roles for ABC transporters as virulence factors in uropathogenic Escherichia coli

Building a nomogram plot based on the nanopore targeted sequencing for predicting urinary tract pathogens and differentiating from colonizing bacteria

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