Bacteria from polymicrobial UTIs
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ABSTRACT:
PROVIDER: PRJEB85553 | ENA |
REPOSITORIES: ENA
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Project description:Catheter-associated urinary tract infections (CAUTI) account for 40% of all nosocomial infections and can lead to significant life-threatening complications such as bacteremia. Microbial biofilms play an important role in the development and pathogenesis of CAUTI, and these biofilms are often polymicrobial. Proteus mirabilis and Enterococcus faecalis are two of the most common causes of CAUTI, and they often persistently co-colonize the catheterized urinary tract. We previously demonstrated that co-culture of E. faecalis with P. mirabilis increased biofilm biomass, antimicrobial resistance, and disease severity. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution of this polymicrobial interaction to CAUTI severity. Through compositional and proteomic biofilm analyses, we determined that the increase in biofilm biomass stems from an increase in the protein fraction of the polymicrobial biofilm matrix. We further observed an enrichment in proteins associated with ornithine and arginine metabolism in polymicrobial biofilms compared to single-species biofilms. By testing mutants of E. faecalis and P. mirabilis, we found that L-ornithine secreted by the E. faecalis ArcD antiporter promotes L-arginine biosynthesis in P. mirabilis via ArgF, which ultimately fuels production of proteins that facilitate contact-dependent interactions to enhance biofilm biomass. We further demonstrate that ArcD and ArgF are not important for urinary tract colonization by either species when alone, but ornithine/arginine interplay is critical for the increased disease severity that occurs during coinfection. This study provides deeper insight into the polymicrobial interactions occurring during CAUTI and highlights how these interactions can have significant impacts on pathogenesis and bacterial persistence.
2025-05-06 | PXD041693 | Pride
Project description:Urinary tract infections (UTIs) are the second most common infections encountered in the pediatric population, second only to respiratory tract infections. UTIs are also a major cause of morbidity and mortality. UTIs can often ascend causing infection in the upper urinary tract or even progress to bacteremia or urosepsis. Urosepsis accounts for 10-30% of septic shock cases and Uropathogenic E.coli (UPEC) is responsible for almost 75% of cases. Therefore, increased understanding of the effects of urosepsis at the cellular and organ specific level will provide the foundation for improvements in clinical care.
2020-10-26 | GSE160038 | GEO
Project description:To describe the transcriptional changes associated with polymicrobial-sepsis induced myocardial depression in wild type and iNOS deficient mice. Keywords: myocardium, contractility, differential gene expression, nitric oxide synthase, infection We compared the transcriptional profile of C57/BL6 WT mice and congenic B6 129P2-Nos2tm1Lau/J mice after 48 hrs of polymicrobial sepsis induced by caecal ligation and perforation. 48 hours after surgery, mice were anaesthetised (intraperitoneal 100 mg/kg ketamine and 10 mg/kg xylazine). The right common carotid artery was cannulated (Millar Mikro-Tip pressure transducing catheter: 1.4F sensor, 2F catheter; Houston TX). Pressure tracings from the aorta and left ventricle were recorded (SonoLAB software; Sonometrics Corp., London Ontario Canada) and analysed using Cardiosoft and Origin 6.0 (Sonometrics Corp., and Microcal Software, Northampton MA). The heart was removed, emptied of blood, and snap frozen.
2010-11-17 | E-GEOD-9667 | biostudies-arrayexpress
Project description:Polymicrobial catheter-associated urinary tract infections (CAUTIs) are a severe clinical burden. CAUTIs promotes colonization by different microbes, including E. faecalis, E. coli, and C. albicans. These mixed biofilms can compromise antimicrobial efficacy and promote resistance. Despite their prevalence, the cross-kingdom dynamics driving these infections within the catheterized bladder remain poorly understood. Using established in vitro and in vivo CAUTI models, we elucidate the complex, environment-dependent interactions governing these multispecies biofilms. We demonstrate that E. coli strongly antagonizes C. albicans, by limiting iron uptake, inhibiting filamentation, and inducing cell death. Crucially, we identify E. faecalis as a protective keystone species that mitigates this antagonism. E. faecalis facilitates multispecies coexistence by acting as a spatial bridge on the urothelium, enabling E. coli and C. albicans to co-localize rather than occupy segregated niches. These mechanistic insights into polymicrobial synergy and competition provide a crucial framework for developing targeted therapeutics against recalcitrant CAUTIs.
2026-04-27 | GSE329180 | GEO
Project description:To describe the transcriptional changes associated with polymicrobial-sepsis induced myocardial depression in wild type and iNOS deficient mice. Keywords: myocardium, contractility, differential gene expression, nitric oxide synthase, infection
2010-11-17 | GSE9667 | GEO
Project description:Urinary tract infections (UTIs) are a very common bacterial infectious disease in humans, and uropathogenic Escherichia coli (UPEC) are the most frequent cause of UTIs. During infection, UPEC must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrated that the small RNA (sRNA) RyfA of UPEC strains was required for resistance to oxidative and osmotic stresses. Inactivation of ryfA in UPEC strain CFT073 decreased urinary tract colonization in CBA/J mice and the ryfA mutant also had reduced production of type 1 and P fimbriae, which are known to be important for UTI. Transcriptomic analysis of the ryfA mutant showed changes in expression of genes associated with general stress responses, metabolism, biofilm formation and genes coding for cell surface proteins. Furthermore, loss of ryfA also reduced UPEC survival in human macrophages. Thus, ryfA plays a key regulatory role in UPEC adaptation to stress, that contributes to UTI and survival in macrophages.
2021-06-23 | GSE157450 | GEO
Project description:Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). A common virulence genotype of UPEC strains responsible for UTIs is yet to be defined, due to the large variation of virulence factors observed in UPEC strains. We hypothesized that studying UPEC functional responses in patients might reveal universal UPEC features that enable pathogenesis. Here we identify a transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients during uncomplicated UTIs. Strikingly, this in vivo gene expression program is marked by upregulation of translational machinery, providing a mechanism for the rapid growth within the host. Our analysis indicates that switching to a more specialized catabolism and scavenging lifestyle in the host allows for the increased translational output. Our study identifies a common transcriptional program underlying UTIs and illuminates the molecular underpinnings that likely facilitate the fast growth rate of UPEC in infected patients.
2019-10-29 | GSE128997 | GEO
Project description:Both Aerococcus urinae (Au) and Globicatella sanguinis (Gs) colonize the human urinary tract and are in the Aerococcaceae family. These rarely pathogenic Gram-positive bacteria were identified in polymicrobial urethral catheter biofilms (CBs) using 16S rDNA and proteomic analyses in this study. For confirming the identities, Au and Gs strains were isolated from small blood agar colonies derived from the CB extracts. Longitudinal surveys of clinical urine specimens revealed their persistence in the urinary tract and recolonization of newly replaced catheters. Dominant CB cohabitating organisms were Enterobacteriaceae, especially Proteus mirabilis and Escherichia coli. The proteomes of Gs and Au profiled from the in vivo milieu suggest that their energy metabolisms rely on glycolytic, heterolactic fermentation and peptide catabolic pathways. Several PTS sugar uptake and oligopeptide ABC transport systems were also highly abundant in the in vivo proteomes of Au and Gs, indicative to adaptations to nutrients available in urine and exfoliated urothelial cells (protein and proteoglycan breakdown products). Differences in Au and Gs metabolisms pertained to citrate lyase and glycogen (only in the Gs proteome), use of Xfp to degrade D-xylulose-5’-phosphate, and synthesis pathways for enzyme cofactors pyridoxal 6’-phosphate and 4’-phosphopantothenate (the latter only in the Au proteome). Interestingly, predicted metal ion (ZnuA-like) uptake systems were abundant in Gs but not in Au in vivo. Au expressed two LPXTG-anchored surface proteins, one predicted to have a pilin D adhesion motif. We describe how two microorganisms not previously characterized metabolically adapt to the milieu in the catheterized human urinary tract. Whether they are true pathogens or bystanders in CBs needs further investigation.
2019-11-13 | PXD012047 | Pride
Project description:Many human infections are polymicrobial in origin, and interactions among community inhabitants shape colonization patterns and pathogenic potential1. However, few interspecies interactions have been functionally dissected at the molecular level or characterized on a systems level. Periodontitis, which is the sixth most prevalent infectious disease worldwide2, ensues from the action of dysbiotic polymicrobial communities3. The keystone pathogen Porphyromonas gingivalis and the accessory pathogen Streptococcus gordonii interact to form communities in vitro and exhibit increased fitness in vivo3, 4. The mechanistic basis of this polymicrobial synergy, however, has not been fully elucidated. Here we show that streptococcal 4 aminobenzoate/para-amino benzoic acid (pABA) is required for maximal accumulation of P. gingivalis in dual species communities. Metabolomic and proteomic data showed that exogenous pABA is utilized for folate biosynthesis, and leads to decreased stress and elevated expression of fimbrial interspecies adhesins. Moreover, pABA increased the colonization and survival of P. gingivalis in a murine oral infection model. However, pABA also caused a reduction in virulence in vivo and suppressed extracellular polysaccharide production by P. gingivalis. Collectively, these data reveal a multidimensional aspect to P. gingivalis-S. gordonii interactions and establish pABA as a critical cue produced by a partner species that enhances fitness of P. gingivalis while diminishing virulence.
2017-09-26 | PXD006153 | Pride