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      The microbiome in urogenital schistosomiasis and induced bladder pathologies

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          Abstract

          Background

          Human schistosomiasis is a highly prevalent neglected tropical disease (NTD) caused by Schistosoma species. Research on the molecular mechanisms influencing the outcomes of bladder infection by Schistosoma haematobium is urgently needed to develop new diagnostics, therapeutics and infection prevention strategies. The objective of the research study was to determine the microbiome features and changes in urine during urogenital schistosomiasis and induced bladder pathologies.

          Methodology

          Seventy participants from Eggua, southwestern Nigeria provided morning urine samples and were screened for urogenital schistosomiasis infection and bladder pathologies in a cross-sectional study. Highthroughput NGS sequencing was carried out, targeting the 16S V3 region. Filtered reads were processed and analyzed in a bioinformatics pipeline.

          Principal findings

          The study participants (36 males and 34 females, between ages 15 and 65) were categorized into four groups according to status of schistosomiasis infection and bladder pathology. Data analytics of the next-generation sequencing reads revealed that Proteobacteria and Firmicutes dominated and had influence on microbiome structure of both non-infected persons and persons with urogenital schistosomiasis. Furthermore, gender and age influenced taxa abundance independent of infection or bladder pathology. Several taxa distinguished urogenital schistosomiasis induced bladder pathologies from urogenital schistosomiasis infection alone and from healthy persons, including known immune-stimulatory taxa such as Fusobacterium, Sphingobacterium and Enterococcus. Some of these significant taxa, especially Sphingobacterium were projected as markers of infection, while several genera including potentially beneficial taxa such as Trabulsiella and Weissella, were markers of the non-infected. Finally, expected changes in protein functional categories were observed to relate to cellular maintenance and lipid metabolism.

          Conclusion

          The urinary microbiome is a factor to be considered in developing biomarkers, diagnostic tools, and new treatment for urogenital schistosomiasis and induced bladder pathologies.

          Author summary

          The human microbiome comprises bacteria (plus viruses, fungi and archeae) inhabiting different sites of the body. They do not specifically cause diseases, but their presence, absence or population influence body functions. We therefore examined such organisms found along the urinary tract, in persons living in a rural community in Nigeria who considered themselves healthy, were infected with the parasite Schistosoma haematobium or had developed bladder complications along with the parasite infection. We found that these groups shared a large portion of the microbiome, but there were microbial species unique to infected persons and those with bladder complication. Some of these were capable of inducing inflammation and could offer less protection to the host. We also predicted pathways that are affected by the difference in the microbiome.

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          Most cited references35

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          Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons

          Background Urine within the urinary tract is commonly regarded as "sterile" in cultivation terms. Here, we present a comprehensive in-depth study of bacterial 16S rDNA sequences associated with urine from healthy females by means of culture-independent high-throughput sequencing techniques. Results Sequencing of the V1V2 and V6 regions of the 16S ribosomal RNA gene using the 454 GS FLX system was performed to characterize the possible bacterial composition in 8 culture-negative (<100,000 CFU/ml) healthy female urine specimens. Sequences were compared to 16S rRNA databases and showed significant diversity, with the predominant genera detected being Lactobacillus, Prevotella and Gardnerella. The bacterial profiles in the female urine samples studied were complex; considerable variation between individuals was observed and a common microbial signature was not evident. Notably, a significant amount of sequences belonging to bacteria with a known pathogenic potential was observed. The number of operational taxonomic units (OTUs) for individual samples varied substantially and was in the range of 20 - 500. Conclusions Normal female urine displays a noticeable and variable bacterial 16S rDNA sequence richness, which includes fastidious and anaerobic bacteria previously shown to be associated with female urogenital pathology.
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            Diverging roles of bacterial siderophores during infection.

            Siderophores are low molecular weight, high affinity iron chelating molecules that are essential virulence factors in many Gram-negative bacterial pathogens. Whereas the chemical structure of siderophores is extremely variable, the function of siderophores has been narrowly defined as the chelation and delivery of iron to bacteria for proliferation. The discovery of the host protein Lipocalin 2, capable of specifically sequestering the siderophore Enterobactin but not its glycosylated-derivative Salmochelin, indicated that diversity in structure could be an immune evasion mechanism that provides functional redundancy during infection. However, there is growing evidence that siderophores are specialized in their iron-acquisition functions, can perturb iron homeostasis in their hosts, and even bind non-iron metals to promote bacterial fitness. The combination of siderophores produced by a pathogen can enable inter-bacterial competition, modulate host cellular pathways, and determine the bacterial "replicative niche" during infection. This review will examine both classical and novel functions of siderophores to address the concept that siderophores are non-redundant virulence factors used to enhance bacterial pathogenesis.
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              An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project.

              , G. Kahlmeter (2002)
              The ECO.SENS study is the first international survey to investigate the prevalence and susceptibility of pathogens causing community-acquired acute uncomplicated urinary tract infections (UTIs). Midstream urine samples were taken for culture and for testing for the presence of leucocytes from 4734 women not older than 65 years presenting with symptoms of acute UTI at 252 community health care centres in 17 countries. Recognized urinary tract pathogens were identified and the susceptibility to 12 antimicrobials determined. Pathogens were present in 3278 (69.2%) patients, Escherichia coli accounting for 77.0% of isolates. In E. coli, 42% of the isolates were resistant to one or more of the 12 antimicrobial drugs investigated. Resistance was most common to ampicillin (29.8%) and sulfamethoxazole (29.1%), followed by trimethoprim (14.8%), trimethoprim/sulfamethoxazole (14.1%) and nalidixic acid (5.4%). Resistance in E. coli to co-amoxiclav, mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin and ciprofloxacin was <3%. However, co-amoxiclav resistance was apparent in Portugal (9.3%) as was resistance to the quinolones, nalidixic acid and ciprofloxacin, in Portugal (11.6% and 5.8%, respectively) and Spain (26.7% and 14.7%, respectively). Overall, Proteus mirabilis were less resistant to ampicillin (16.1%) and more resistant to trimethoprim (25.5%) than E. coli, whereas Klebsiella spp. were more resistant to ampicillin (83.5%) and fosfomycin (56.7%). 'Other Enterobacteriaceae' were more resistant to the broad spectrum beta-lactams (ampicillin 45.9%, co-amoxiclav 21.3% and cefadroxil 24.6%), nitrofurantoin (40.2%) and fosfomycin (15.6%). In Staphylococcus saprophyticus resistance development was rare. Overall, antimicrobial resistance was lowest in the Nordic countries and Austria and highest in Portugal and Spain.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Methodology
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                9 August 2017
                August 2017
                : 11
                : 8
                : e0005826
                Affiliations
                [1 ] Cell Biology & Genetics Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria
                [2 ] National Centre for Cell Science, Pune, India
                [3 ] Department of Radiology, University of Ibadan, Nigeria
                [4 ] Bethune-Cookman University, Daytona Beach, Florida, United States of America
                George Washington University, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-9444-685X
                Article
                PNTD-D-17-00137
                10.1371/journal.pntd.0005826
                5565189
                28793309
                eaab4be2-07ff-4beb-a054-a7a618045724
                © 2017 Adebayo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 January 2017
                : 21 July 2017
                Page count
                Figures: 8, Tables: 1, Pages: 22
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100007042, Third World Academy of Sciences;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100004423, World Health Organization;
                Award ID: B40394
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: HRD-1435186
                Award Recipient :
                ASA received travel support from The World Academy Academy of Sciences (TWAS)/ Department of Biotechnology (India) Postgraduate Fellowship in the course of the research. RDI acknowledges the award HRD-1435186 from the U.S. National Science Foundation. CIA acknowledges the World Health Organisation short term training grant B40394. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Parasitic Diseases
                Helminth Infections
                Schistosomiasis
                Urogenital Schistosomiasis
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Schistosomiasis
                Urogenital Schistosomiasis
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Anatomy
                Renal System
                Bladder
                Medicine and Health Sciences
                Anatomy
                Renal System
                Bladder
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Urine
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Urine
                Biology and Life Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Pseudomonas Infections
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Enterococcus Infections
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Fusobacterium Infections
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Acinetobacter Infections
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-08-21
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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