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Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract

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  • Authors: Kimberly A. Kline1, Amanda L. Lewis2
  • Editors: Matthew A. Mulvey3, Ann E. Stapleton4, David J. Klumpp5
    Affiliations: 1: Singapore Centre on Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore 637551; 2: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110; 3: University of Utah, Salt Lake City, UT; 4: University of Washington, Seattle, WA; 5: Northwestern University, Chicago, IL
  • Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.UTI-0012-2012
  • Received 23 September 2012 Accepted 13 October 2015 Published 11 March 2016
  • Amanda L. Lewis, [email protected]; Kimberly A. Kline, [email protected]
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  • Abstract:

    Gram-positive bacteria are a common cause of urinary-tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI. Here we review the epidemiology, virulence mechanisms, and host response to the most frequently isolated Gram-positive uropathogens: , and . We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including , and . The literature strongly suggests that urologic diseases involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria. We herein review the risk factors and recent evidence for mechanisms of bacterial synergy in experimental models of polymicrobial UTI. Recent experimental data has demonstrated that, despite being cleared quickly from the bladder, some Gram-positive bacteria can impact pathogenic outcomes of co-infecting organisms. When taken together, the available evidence argues that Gram-positive bacteria are important uropathogens in their own right, but that some can be easily overlooked because they are missed by routine diagnostic methods. Finally, a growing body of evidence demonstrates that a surprising variety of fastidious Gram-positive bacteria may either reside in or be regularly exposed to the urinary tract and further suggests that their presence is widespread among women, as well as men. Experimental studies in this area are needed; however, there is a growing appreciation that the composition of bacteria found in the bladder could be a potentially important determinant in urologic disease, including susceptibility to UTI.

  • Citation: Kline K, Lewis A. 2016. Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract. Microbiol Spectrum 4(2):UTI-0012-2012. doi:10.1128/microbiolspec.UTI-0012-2012.


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Gram-positive bacteria are a common cause of urinary-tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI. Here we review the epidemiology, virulence mechanisms, and host response to the most frequently isolated Gram-positive uropathogens: , and . We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including , and . The literature strongly suggests that urologic diseases involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria. We herein review the risk factors and recent evidence for mechanisms of bacterial synergy in experimental models of polymicrobial UTI. Recent experimental data has demonstrated that, despite being cleared quickly from the bladder, some Gram-positive bacteria can impact pathogenic outcomes of co-infecting organisms. When taken together, the available evidence argues that Gram-positive bacteria are important uropathogens in their own right, but that some can be easily overlooked because they are missed by routine diagnostic methods. Finally, a growing body of evidence demonstrates that a surprising variety of fastidious Gram-positive bacteria may either reside in or be regularly exposed to the urinary tract and further suggests that their presence is widespread among women, as well as men. Experimental studies in this area are needed; however, there is a growing appreciation that the composition of bacteria found in the bladder could be a potentially important determinant in urologic disease, including susceptibility to UTI.

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virulence factors. Secreted surface proteins: Aas, possesses N-terminal signal sequence, but no motifs such as a transmembrane domain, LPXTG sortase-recognition motif, or proline/glycine-rich cell wall-spanning domain to indicate the mode of attachment to the cell surface after translocation across the membrane (indicated by the purple question marks) ( 72 ). Immuno-electron microscopy shows Aas as part of a fuzzy surface layer that is absent when Aas is not expressed ( 75 ). Ssp has a YSIRK-containing signal sequence but no sortase-recognition motif so its mode of attachment to the cell surface is uncertain (indicated by the red question mark); it is easily sheared from the cell surface. Electron microscopy and immuno-electron micrographs also show Ssp to exist as part of fuzzy surface layer, apparently consisting of 50–75nm fibrillar structures; the nature of these fibers in not known ( 75 , 76 ). UafA, SdrI, SssF, and UafB contain an LPXTG motif and are predicted to be covalently attached to the cell wall ( 78 , 79 , 81 ). The small arrows near the membrane-anchored sortase enzymes indicate the two-step transpeptidation reaction whereby sortase substrates are first cleaved within the LPXTG motif to create a sortase-substrate intermediate (and releasing the membrane domain and positively charged cytoplasmic tail, indicated by the straight line in the membrane) that is then resolved, resulting in covalent linkage of the substrate to the cell wall ( 328 ). UafB is genetically linked to accessory secretion genes and that are predicted to encode a dedicated accessory secretion system for UafB ( 79 ). Cytoplasmic enzymes that promote survival in urine ( 329 , 330 ).

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.UTI-0012-2012
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Gram-positive inhabitants and pathogens of the human urinary tract. Approximate phylogenetic relationships between Gram-positive bacteria are illustrated in this schematic representation. Please refer to the text and Table 1 for additional information and references describing these genera as uropathogens or inhabitants of the human urinary tract. On the left, and belong to the order which together with the orders belong to the class (a.k.a. “high-GC Gram-positive bacteria”). belongs to the order and the class . The classes and both belong to the phylum . The remaining genera, with the exception of belong to the phylum . Whereas , , and belong to the order and the class , and belong to the order and the class . Members of the order (, , , and ), are also classified as . The genus is also a member of the , but belongs to the class and order and respectively. On the other hand, belongs to the phylum , the class and the order .

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.UTI-0012-2012
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Transmission-electron micrographs of several urogenital isolates from the phylum . Strains grown for 24–48 hours underwent negative staining with uranyl acetate and were examined by TEM. These strains were isolated from the urine or vaginas of pregnant or nonpregnant women and are available through BEI resources. Strain names are as follows: MJR8396A; CMW7705A; CMW7778A; MJR8628B; , MJR7694. Scale bars are 500 nm. Shaded backgrounds contain images of the same strain.

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.UTI-0012-2012
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Genera of Gram-positive human urinary tract inhabitants and pathogens detected by culture-dependent and –independent techniques

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.UTI-0012-2012

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