Significance of the
            <scp>d</scp>
            -Serine-Deaminase and
            <scp>d</scp>
            -Serine Metabolism of Staphylococcus saprophyticus for Virulence

Korte-Berwanger, Miriam; Sakιnç, Türkân; Kline, Kimberly; Nielsen, Hailyn V.; Hultgren, Scott J.; Gatermann, Sören

doi:10.1128/iai.00599-13

Cited by 29 publications

(24 citation statements)

References 55 publications

(45 reference statements)

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“…The ability of S. saprophyticus to tolerate high concentrations of D-serine that occur in the urine is conferred by D-serine deaminase, found in S. saprophyticus but in no other staphylococci [91] (Figure 1C). S. saprophyticus upregulates the virulence determinant Ssp in the presence of D-serine, and D-serine deaminase mutants are outcompeted by the isogenic wild type strain in the kidneys in a murine model of UTI [92]. S. saprophyticus express a capsule, whose encoding genetic locus in the sequenced strain is found on an SCC genetic element and whose genetic arrangement is similar to the S. aureus cap5 ( cap8 ) locus [78].…”

Section: Urinary Tract Infection Caused By Staphylococcimentioning

confidence: 99%

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

2016

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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: Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae. We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including Aerococcus, Corynebacterium, Actinobaculum, and Gardnerella. 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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Section: Urinary Tract Infection Caused By Staphylococcimentioning

confidence: 99%

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

2016

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“…d ‐serine deaminase mutants have a marked disadvantage in a mouse model for UTI (Korte‐Berwanger et al . ). We are therefore planning to look at the effects of these plant preparations on the uptake and metabolism of d ‐serine by S. saprophyticus .…”

Section: Discussionmentioning

confidence: 97%

“…These include several adhesins, a surface-associated lipase and a D-serine deaminase that allows it to tolerate inhibitory concentrations of this compound. D-serine deaminase mutants have a marked disadvantage in a mouse model for UTI (Korte-Berwanger et al 2013). We are therefore planning to look at the effects of these plant preparations on the uptake and metabolism of D-serine by S. saprophyticus.…”

Section: Discussionmentioning

confidence: 99%

Limited effectiveness of over-the-counter plant preparations used for the treatment of urinary tract infections as inhibitors of the urease activity fromStaphylococcus saprophyticus

Deutch

2017

J Appl Microbiol

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“…One of the few genes that was upregulated in humans compared to mice was dsdX , which encodes a D-serine transporter. Interestingly, D-serine is present in micromolar amounts in human urine (29), D-serine utilization is associated with uropathogenic strains (30, 31) and accumulation of D-serine leads to a “hypervirulent” phenotype (31, 32) in the urinary tract. Since there was an upregulation in D-serine transport, and not in the deaminase required for its breakdown ( dsdA ), perhaps this presents a mechanism to increase the intracellular levels of D-serine specific to hUTI.…”

Section: Discussionmentioning

confidence: 99%

The Gene Expression Profile of UropathogenicEscherichia coliin Women with Uncomplicated Urinary Tract Infections Is Recapitulated in the Mouse Model

Frick-Cheng

Sintsova

Smith

et al. 2020

Preprint

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16Uropathogenic Escherichia coli (UPEC) is the primary causative agent of uncomplicated 17 urinary tract infections (UTIs). UPEC fitness and virulence determinants have been evaluated in a 18 variety of laboratory settings that include a well-established mouse model of UTI. However, the 19 extent to which bacterial physiology differs between experimental models and human infections 20 remains largely understudied. To address this important question, we compared the transcriptomes 21 of three different UPEC isolates in human infection and a variety of laboratory conditions 22including LB culture, filter-sterilized urine culture, and the UTI mouse model. We observed high 23 correlation in gene expression between the mouse model and human infection in all three strains 24 examined (Pearson correlation coefficient of 0.86-0.87). Only 175 of 3,266 (5.4%) genes shared 25 by all three strains had significantly different expression levels, with the majority of them (145 26 genes) down-regulated in patients. Importantly, gene expression of both canonical virulence 27 factors and metabolic machinery were highly similar between the mouse model and human 28 infection, while the in vitro conditions displayed more substantial differences. Interestingly, 29 comparison of gene expression between the mouse model and human infection hint at differences 30 in bladder oxygenation as well as nutrient composition. In summary, our work strongly validates 31 the continued use of this mouse model for the study of the pathogenesis of human UTI. 32 33 Importance 34 Different experimental models have been used to study UPEC pathogenesis including in vitro 35cultures in different media, tissue culture, as well as mouse models of infection. The latter is 36 especially important since it allows evaluation of mechanisms of pathogenesis and potential 37 therapeutic strategies against UPEC. Bacterial physiology is greatly shaped by environment and it 38 is therefore critical to understand how closely bacterial physiology in any experimental model 39 relates to human infection. In this study, we found a very strong correlation in bacterial gene 40 expression between the mouse model and human UTI using identical strains, suggesting that the 41 mouse model accurately mimics human infection, definitively supporting its continued use in UTI 42 research. 43

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Significance of the d -Serine-Deaminase and d -Serine Metabolism of Staphylococcus saprophyticus for Virulence

Cited by 29 publications

References 55 publications

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

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

Limited effectiveness of over-the-counter plant preparations used for the treatment of urinary tract infections as inhibitors of the urease activity fromStaphylococcus saprophyticus

The Gene Expression Profile of UropathogenicEscherichia coliin Women with Uncomplicated Urinary Tract Infections Is Recapitulated in the Mouse Model

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