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      Enterococcus faecalis Polymicrobial Interactions Facilitate Biofilm Formation, Antibiotic Recalcitrance, and Persistent Colonization of the Catheterized Urinary Tract

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          Abstract

          Indwelling urinary catheters are common in health care settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, we identified Enterococcus faecalis and Proteus mirabilis as the most prevalent and persistent co-colonizers. Clinical isolates of both species successfully co-colonized in a murine model of CAUTI, and they were observed to co-localize on catheter biofilms during infection. We further demonstrate that P. mirabilis preferentially adheres to E. faecalis during biofilm formation, and that contact-dependent interactions between E. faecalis and P. mirabilis facilitate establishment of a robust biofilm architecture that enhances antimicrobial resistance for both species. E. faecalis may therefore act as a pioneer species on urinary catheters, establishing an ideal surface for persistent colonization by more traditional pathogens such as P. mirabilis.

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          Most cited references62

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          Urinary tract infections: epidemiology, mechanisms of infection and treatment options.

          Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
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            Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria.

            Biofilms are surface-attached groups of microbial cells encased in an extracellular matrix that are significantly less susceptible to antimicrobial agents than non-adherent, planktonic cells. Biofilm-based infections are, as a result, extremely difficult to cure. A wide range of molecular mechanisms contribute to the high degree of recalcitrance that is characteristic of biofilm communities. These mechanisms include, among others, interaction of antimicrobials with biofilm matrix components, reduced growth rates and the various actions of specific genetic determinants of antibiotic resistance and tolerance. Alone, each of these mechanisms only partially accounts for the increased antimicrobial recalcitrance observed in biofilms. Acting in concert, however, these defences help to ensure the survival of biofilm cells in the face of even the most aggressive antimicrobial treatment regimens. This review summarises both historical and recent scientific data in support of the known biofilm resistance and tolerance mechanisms. Additionally, suggestions for future work in the field are provided.
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              Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America

              Guidelines for the diagnosis, prevention, and management of persons with catheter-associated urinary tract infection (CA-UTI), both symptomatic and asymptomatic, were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic criteria, strategies to reduce the risk of CA-UTIs, strategies that have not been found to reduce the incidence of urinary infections, and management strategies for patients with catheter-associated asymptomatic bacteriuria or symptomatic urinary tract infection. These guidelines are intended for use by physicians in all medical specialties who perform direct patient care, with an emphasis on the care of patients in hospitals and long-term care facilities.
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                Author and article information

                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                13 October 2020
                October 2020
                : 9
                : 10
                : 835
                Affiliations
                [1 ]Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, NY 14203, USA; jgaston2@ 123456buffalo.edu (J.R.G.); cs285@ 123456buffalo.edu (C.M.S.); laurengu@ 123456buffalo.edu (L.B.G.)
                [2 ]Department of Biological Sciences, College of Science, Notre Dame University, IN 15701, USA; mander40@ 123456nd.edu
                [3 ]Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, NY 14203, USA; aj77@ 123456buffalo.edu (A.O.J.); klbair@ 123456buffalo.edu (K.L.B.); ashleywh@ 123456buffalo.edu (A.N.W.); albrauer@ 123456buffalo.edu (A.L.B.); bslearma@ 123456buffalo.edu (B.S.L.)
                Author notes
                [* ]Correspondence: afloresm@ 123456nd.edu (A.L.F.-M.); chelsiea@ 123456buffalo.edu (C.E.A.)
                [†]

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0002-0489-086X
                https://orcid.org/0000-0003-3567-2176
                https://orcid.org/0000-0003-1672-1761
                https://orcid.org/0000-0002-1686-1695
                https://orcid.org/0000-0003-3680-0061
                https://orcid.org/0000-0003-4610-4246
                https://orcid.org/0000-0002-2165-2759
                Article
                pathogens-09-00835
                10.3390/pathogens9100835
                7602121
                33066191
                5825daa7-60a0-4430-85a9-eaad1de2a364
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 September 2020
                : 12 October 2020
                Categories
                Article

                proteus mirabilis,enterococcus faecalis,polymicrobial,biofilm,catheter,urinary tract infection

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