Foodborne Origin and Local and Global Spread of Staphylococcus saprophyticus Causing Human Urinary Tract Infections.
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ABSTRACT:
SUBMITTER: Lawal OU
PROVIDER: S-EPMC7920669 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The in vitro activities of gepotidacin and comparator agents against 3,560 Escherichia coli and 344 Staphylococcus saprophyticus collected from female (81.1%) and male (18.9%) patients with urinary tract infections (UTIs) in a global prospective surveillance program in 2019 to 2020 were determined. Isolates collected from 92 medical centers in 25 countries, including the United States, Europe, Latin America, and Japan, were tested for susceptibility by reference methods in a central monitoring laboratory. Gepotidacin inhibited 98.0% (3,488/3,560 isolates) of E. coli and 100% (344/344 isolates) of S. saprophyticus at gepotidacin concentrations of ≤4 μg/mL and ≤0.25 μg/mL, respectively. This activity was largely unaffected with isolates that demonstrated resistance phenotypes to other oral standard-of-care antibiotics, including amoxicillin-clavulanic acid, cephalosporins, fluoroquinolones, fosfomycin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Gepotidacin also inhibited 94.3% (581/616 isolates) of E. coli isolates with an extended-spectrum β-lactamase-producing phenotype, 97.2% (1,085/1,129 isolates) of E. coli isolates resistant to ciprofloxacin, 96.1% (874/899) of E. coli isolates resistant to trimethoprim-sulfamethoxazole, and 96.3% (235/244 isolates) of multidrug-resistant E. coli isolates at gepotidacin concentrations of ≤4 μg/mL. In summary, gepotidacin demonstrated potent activity against a large collection of contemporary UTI E. coli and S. saprophyticus strains collected from patients worldwide. These data support the further clinical development of gepotidacin as a potential treatment option for patients with uncomplicated UTIs.
| S-EPMC10112209 | biostudies-literature
Project description:ObjectiveThe purpose of the present study was to investigate the biofilm production, and the presence of virulence genes and biochemical characteristics among the S. saprophyticus clinical isolates. A total of 35 clinical isolates of S. saprophyticus were collected from patients referred to several hospitals. By the crystal violet staining method, the capability of biofilm formation was performed. The genes associated with surface of S. saprophyticus were investigated by the PCR-sequencing techniques. Hemagglutination and lipase activity assays were also performed.ResultsThe results of crystal violet staining assay showed that 32 isolates (91%) form biofilm. Moreover, seven (20%), 13 (37%), and 12(34%) isolates were categorized as weak, moderate, and strong biofilm producers, respectively. virulence genes including UafA, Aas and Ssp had an overall prevalence of 88%, 91% and 80%, respectively. None of the isolates exhibited lipolytic activities. Regarding hemagglutination properties, only 11 (31%) isolates demonstrated hemagglutination of sheep erythrocytes. The results of this study indicate a high prevalence of UafA and Aas genes that can enhance the pathogenicity of S. saprophyticus, and Identification and better understanding of the functions of these genes can be used for therapeutic purposes. Maybe in the future we will be switch to anti-adhesion therapy because of drug resistance.
| S-EPMC10496302 | biostudies-literature
Project description:Staphylococcus saprophyticus is a uropathogenic Staphylococcus frequently isolated from young female outpatients presenting with uncomplicated urinary tract infections. We sequenced the whole genome of S. saprophyticus type strain ATCC 15305, which harbors a circular chromosome of 2,516,575 bp with 2,446 ORFs and two plasmids. Comparative genomic analyses with the strains of two other species, Staphylococcus aureus and Staphylococcus epidermidis, as well as experimental data, revealed the following characteristics of the S. saprophyticus genome. S. saprophyticus does not possess any virulence factors found in S. aureus, such as coagulase, enterotoxins, exoenzymes, and extracellular matrix-binding proteins, although it does have a remarkable paralog expansion of transport systems related to highly variable ion contents in the urinary environment. A further unique feature is that only a single ORF is predictable as a cell wall-anchored protein, and it shows positive hemagglutination and adherence to human bladder cell associated with initial colonization in the urinary tract. It also shows significantly high urease activity in S. saprophyticus. The uropathogenicity of S. saprophyticus can be attributed to its genome that is needed for its survival in the human urinary tract by means of novel cell wall-anchored adhesin and redundant uro-adaptive transport systems, together with urease.
| S-EPMC1201578 | biostudies-literature
Project description:Objectives: To investigate pivmecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus-considered non-susceptible to mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivmecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect-symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect-elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ?103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18-55 years) were empirically treated with pivmecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: Pivmecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised.
| S-EPMC6628187 | biostudies-literature
Project description:Staphylococcus saprophyticus is a common pathogen of the urinary tract, a heavy metal-rich environment, but information regarding its heavy metal resistance is unknown. We investigated 422 S. saprophyticus isolates from human infection and colonization/contamination, animals, and environmental sources for resistance to copper, zinc, arsenic, and cadmium using the agar dilution method. To identify the genes associated with metal resistance and assess possible links to pathogenicity, we accessed the whole-genome sequence of all isolates and used in silico and pangenome-wide association approaches. The MIC values for copper and zinc were uniformly high (1,600 mg/liter). Genes encoding copper efflux pumps (copA, copB, copZ, mco, and csoR) and zinc transporters (zinT, czrAB, znuBC, and zur) were abundant in the population (20 to 100%). Arsenic and cadmium showed various susceptibility levels. Genes encoding the ars operon (arsRDABC), an ABC transporter and a two-component permease, were linked to resistance to arsenic (MICs ≥ 1,600 mg/liter; 14% [58/422]; P < 0.05). At least three cad genes (cadA or cadC and cadD-cadX or czrC) and genes encoding multidrug efflux pumps and hyperosmoregulation in acidified conditions were associated with resistance to cadmium (MICs ≥ 200 mg/liter; 20% [85/422]; P < 0.05). These resistance genes were frequently carried by mobile genetic elements. Resistance to arsenic and cadmium were linked to human infection and a clonal lineage originating in animals (P < 0.05). Altogether, S. saprophyticus was highly resistant to heavy metals and accumulated multiple metal resistance determinants. The highest arsenic and cadmium resistance levels were associated with infection, suggesting resistance to these metals is relevant for S. saprophyticus pathogenicity.
| S-EPMC8218656 | biostudies-literature
Project description:The virulence determinants of uropathogenic Escherichia coli have been studied extensively over the years, but relatively little is known about what differentiates isolates causing various types of urinary tract infections. In this study, we compared the genomic profiles of 45 strains from a range of different clinical backgrounds, i.e., urosepsis, pyelonephritis, cystitis, and asymptomatic bacteriuria (ABU), using comparative genomic hybridization analysis. A microarray based on 31 complete E. coli sequences was used. It emerged that there is little correlation between the genotypes of the strains and their disease categories but strong correlation between the genotype and the phylogenetic group association. Also, very few genetic differences may exist between isolates causing symptomatic and asymptomatic infections. Only relatively few genes that could potentially differentiate between the individual disease categories were identified. Among these were two genomic islands, namely, pathogenicity island (PAI)-CFT073-serU and PAI-CFT073-pheU, which were significantly more associated with the pyelonephritis and urosepsis isolates than with the ABU and cystitis isolates. These two islands harbor genes encoding virulence factors, such as P fimbriae (pyelonephritis-associated fimbriae) and an important immunomodulatory protein, TcpC. It seems that both urovirulence and growth fitness can be attributed to an assortment of genes rather than to a specific gene set. Taken together, urovirulence and fitness are the results of the interplay of a mixture of factors taken from a rich menu of genes.
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Project description:Staphylococcus saprophyticus is a uropathogenic bacterium that causes acute uncomplicated urinary tract infections, particularly in female outpatients. We investigated the dissemination and antimicrobial susceptibilities of 101 S. saprophyticus isolates from the genitourinary tracts of patients in Japan. Eight of these isolates were mecA positive and showed beta-lactam resistance. Pulsed-field gel electrophoresis showed that only some isolates were isogenic, indicating that the mecA gene was apparently acquired independently by mecA-positive isolates through staphylococcal cassette chromosome mec (SCCmec). Type determination of SCCmec by multiplex PCR showed a nontypeable element in the eight mecA-positive isolates. Sequence analysis of the entire SCCmec element from a prototype S. saprophyticus strain revealed that it was nontypeable with the current SCCmec classification due to the novel composition of the class A mec gene complex (IS431-mecA-mecR1-mecI genes) and the ccrA1/ccrB3 gene complex. Intriguingly, the attachment sites of SCCmec are similar to those of type I SCCmec in S. aureus NCTC 10442. Furthermore, the genes around the mec gene complex are similar to those of type II/III SCCmec in S. aureus, while those around the ccr gene complex are similar to those of SCC15305RM found in S. saprophyticus ATCC 15305. In comparison with known SCCmec elements, this S. saprophyticus SCCmec is a novel type.
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Project description:Given the high frequency of urinary tract infections (UTIs) and their recurrence, there is keen interest in developing effective UTI vaccines. Currently, most vaccine studies, including those in humans, involve parenteral vaccination aimed at evoking and sustaining elevated levels of systemic antibody directed at the uropathogens. In view of recent reports of aberrant Th2-biased bladder immune responses to infection, we hypothesized that immunizing mice intravesically with antigens from uropathogenic Escherichia coli (UPEC) combined with a Th1-skewing adjuvant could correct this defect and promote protection against UTIs. Here we report that compared with mice immunized subcutaneously with this vaccine combination, intravesically immunized mice were markedly more protected from UTIs because of their distinctive ability to recruit Th1 cells into the bladder. This mode of vaccination was effective even in mice that experienced multiple UTIs and displayed pronounced aberrant bladder immune responses. Thus, intravesical vaccination with one or more UPEC antigens to induce bladder Th1 responses represents a superior strategy to combat UTIs, especially in UTI-prone subjects.
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Project description:Escherichia coli sequence types (STs) 69, 73, 95, and 131 are collectively responsible for a large proportion of E. coli urinary tract and bloodstream infections, and they differ markedly in their antibiotic susceptibilities. Here, we describe a novel PCR method to rapidly detect and distinguish these lineages. Three hundred eighteen published E. coli genomes were compared in order to identify signature sequences unique to each of the four major STs. The specificities of these sequences were assessed in silico by seeking them in an additional 98 genomes. A PCR assay was designed to amplify size-distinguishable fragments unique to the four lineages and was validated using 515 E. coli isolates of known STs. Genome comparisons identified 22 regions ranging in size from 335 bp to 26.5 kb that are unique to one or more of the four predominant E. coli STs, with two to 10 specific regions per ST. These regions predominantly harbor genes encoding hypothetical proteins and are within or adjacent to prophage sequences. Most (13/22) were highly conserved (>96.5% identity) in the genomes of their respective ST. The new assay correctly identified all 142 representatives of the four major STs in the validation set (n = 515), with only two ST12 isolates misidentified as ST95. Compared with MLST, the assay has 100% sensitivity and 99.5% specificity. The rapid identification of major extraintestinal E. coli STs will benefit future epidemiological studies and could be developed to tailor antibiotic therapy to the different susceptibilities of these dominant lineages.
| S-EPMC4290915 | biostudies-literature
Project description:The present study investigated the incidence of hyperammonemia in urinary tract infections and explored the utility of urinary obstruction relief and antimicrobial administration to improve hyperammonemia.This was an observational study. Subjects were patients who were diagnosed with urinary tract infection and hospitalized between June 2008 and June 2009. We measured plasma ammonia levels on admission in patients who were clinically diagnosed with urinary tract infection and hospitalized. We assessed each patient's level of consciousness on admission using the Glasgow Coma Scale (GCS) and performed urine and blood cultures. We also assessed hearing prior to hospitalization using the Eastern Cooperative Oncology Group performance status (ECOG-PS). In cases with high ammonia levels on admission, plasma ammonia and GCS were measured 24 hours and 5-7 days later.Sixty-seven candidates were enrolled; of these, 60 cases (89.6%) with bacterial cell counts ≥10(4) CFU/mL were studied. Five cases (8.3%) presented with high plasma ammonia levels. Cases with hyperammonemia were significantly more likely to present with low GCS scores and urinary retention rate. All five cases received antimicrobial therapy with an indwelling bladder catheter to relieve urinary retention. The case 5 patient died shortly after admission due to complicated aspiration pneumonia; in the remaining cases, plasma ammonia levels were rapidly normalized and the level of consciousness improved.The occurrence of hyperammonemia in urinary tract infections is not rare. The cause of hyperammonemia is urinary retention obstruction. Therefore, along with antimicrobial administration, relief of obstruction is important for the treatment of hyperammonemia caused by this mechanism.
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