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      The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury – a pilot study

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          Abstract

          Background

          In the past urine was considered sterile. Through the introduction of next generation sequencing, it has become clear that a urinary microbiome exists. Acute kidney injury (AKI) represents a major threat to kidney transplant recipients. Remarkable changes in the urinary metabolome occur during AKI, which may influence the urinary microbiome. To our knowledge, this is the first study that examines the urinary microbiome in renal transplant recipients (RTX) and non-transplant recipients (nRTX) at time of AKI.

          Methods

          In this cross-sectional pilot-study the urinary microbiome of 21 RTX and 9 nRTX with AKI was examined. Clean catch morning urine samples were obtained from all patients on the first day of AKI diagnosis. AKI was defined according to KDIGO guidelines. Urinary microbiota and the urinary metabolome during AKI were assessed in one patient. 16S rRNA sequencing was performed. Sequences were processed using UPARSE-pipeline for operational taxonomic units (OTU) and taxon finding.

          Results

          We successfully extracted and sequenced bacterial DNA from 100% of the urine samples. All 30 patients revealed at least 106,138 reads. 319 OTU and 211 different genera were identified. The microbiotic diversity richness in the RTX group was no different from the nRTX group. Eighteen genera were solely present in nRTX and 7 in RTX.

          Conclusions

          The urinary microbiome at time of AKI showed different bacterial genera in RTX compared to nRTX. The nRTX group exhibited no different diversity to the RTX group. Irrespective of the status of a previous renal transplantation, the urinary microbiome comprised > 210 different genera. An intraindividual change in microbiota diversity and richness was observed in one study patient during recovery from AKI.

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          Most cited references32

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          Novel soil bacteria possess diverse genes for secondary metabolite biosynthesis

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            Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity?

            Objectives: Traditionally, the urinary tract has been thought to be sterile in the absence of a clinically identifiable infection. However, recent evidence suggests that the urinary tract harbors a variety of bacterial species, known collectively as the urinary microbiome, even when clinical cultures are negative. Whether these bacteria promote urinary health or contribute to urinary tract disease remains unknown. Emerging evidence indicates that a shift in the urinary microbiome may play an important role in urgency urinary incontinence (UUI). The goal of this prospective pilot study was to determine how the urinary microbiome is different between women with and without UUI. We also sought to identify if characteristics of the urinary microbiome are associated with UUI severity. Methods: We collected urine from clinically well-characterized women with UUI (n = 10) and normal bladder function (n = 10) using a transurethral catheter to avoid bacterial contamination from external tissue. To characterize the resident microbial community, we amplified the bacterial 16S rRNA gene by PCR and performed sequencing using Illumina MiSeq. Sequences were processed using the workflow package QIIME. We identified bacteria that had differential relative abundance between UUI and controls using DESeq2 to fit generalized linear models based on the negative binomial distribution. We also identified relationships between the diversity of the urinary microbiome and severity of UUI symptoms with Pearson's correlation coefficient. Results: We successfully extracted and sequenced bacterial DNA from 95% of the urine samples and identified that there is a polymicrobial community in the female bladder in both healthy controls and women with UUI. We found the relative abundance of 14 bacteria significantly differed between control and UUI samples. Furthermore, we established that an increase in UUI symptom severity is associated with a decrease in microbial diversity in women with UUI. Conclusions: Our study provides further characterization of the urinary microbiome in both healthy controls and extensively phenotyped women with UUI. Our results also suggest that the urinary microbiome may play an important role in the pathophysiology of UUI and that the loss of microbial diversity may be associated with clinical severity.
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              Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective

              Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.
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                Author and article information

                Contributors
                daniela.knafl@meduniwien.ac.at
                peter.pichler@meduniwien.ac.at
                alexander.zimprich@meduniwien.ac.at
                christoph.hotzy@meduniwien.ac.at
                wolfgang.barousch@meduniwien.ac.at
                rita.lang@meduniwien.ac.at
                elisabeth.lobmeyr@meduniwien.ac.at
                sabina.baumgartner-parzer@meduniwien.ac.at
                ludwig.wagner@meduniwien.ac.at
                wolfgang.winnicki@meduniwien.ac.at
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                6 April 2020
                6 April 2020
                2020
                : 21
                : 117
                Affiliations
                [1 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Internal Medicine III, Division of Nephrology and Dialysis, , Medical University of Vienna, ; Waehringer Guertel 18-20, 1090 Vienna, Austria
                [2 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Neurology, , Medical University of Vienna, ; Vienna, Austria
                [3 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Laboratory Medicine, Division of Clinical Microbiology, , Medical University of Vienna, ; Vienna, Austria
                [4 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Internal Medicine III, Division of Endocrinology and Metabolism, , Medical University of Vienna, ; Vienna, Austria
                [5 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Emergency Medicine, , Medical University of Vienna, ; Vienna, Austria
                Article
                1773
                10.1186/s12882-020-01773-1
                7133001
                32252662
                d5d29fce-9f10-421f-8ccd-2cba19e9cfde
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 13 July 2019
                : 19 March 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Nephrology
                urinary microbiome,kidney transplantation,acute kidney injury (aki),urinary tract infection,microbiome research

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