scholarly journals Adaptation in a fibronectin binding autolysin ofStaphylococcus saprophyticus

2017 ◽  
Author(s):  
Tatum D. Mortimer ◽  
Douglas S. Annis ◽  
Mary B. O’Neill ◽  
Lindsey L. Bohr ◽  
Tracy M. Smith ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Pathogenic Bacteria ◽  
Human Microbiome ◽  
Invasive Disease ◽  
Human Infection ◽  
Gene Encoding ◽  
Staphylococcus Saprophyticus ◽  
Evolutionary Genomic ◽  
Tract Infections

AbstractHuman-pathogenic bacteria are found in a variety of niches, including free-living, zoonotic, and microbiome environments. Identifying bacterial adaptions that enable invasive disease is an important means of gaining insight into the molecular basis of pathogenesis and understanding pathogen emergence.Staphylococcus saprophyticus, a leading cause of urinary tract infections, can be found in the environment, food, animals, and the human microbiome. We identified a selective sweep in the gene encoding the Aas adhesin, a key virulence factor that binds host fibronectin. We hypothesize that the mutation under selection (aas_2206A>C) facilitates colonization of the urinary tract, an environment where bacteria are subject to strong shearing forces. The mutation appears to have enabled emergence and expansion of a human pathogenic lineage ofS. saprophyticus. These results demonstrate the power of evolutionary genomic approaches in discovering the genetic basis of virulence and emphasize the pleiotropy and adaptability of bacteria occupying diverse niches.ImportanceStaphylococcus saprophyticusis an important cause of urinary tract infections (UTI) in women, which are common, can be severe, and are associated with significant impacts to public health. In addition to being a cause of human UTI,S. saprophyticuscan be found in the environment, in food, and associated with animals. After discovering that UTI strains ofS. saprophyticusare for the most part closely related to each other, we sought to determine whether these strains are specially adapted to cause disease in humans. We found evidence suggesting that a mutation in the geneaasis advantageous in the context of human infection. We hypothesize that the mutation allowsS. saprophyticusto survive better in the human urinary tract. These results show how bacteria found in the environment can evolve to cause disease.

scholarly journals Adaptation in a Fibronectin Binding Autolysin of Staphylococcus saprophyticus

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Tatum D. Mortimer ◽  
Douglas S. Annis ◽  
Mary B. O’Neill ◽  
Lindsey L. Bohr ◽  
Tracy M. Smith ◽  
...  
Keyword(s):  
Public Health ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Pathogenic Bacteria ◽  
Human Microbiome ◽  
Invasive Disease ◽  
Human Infection ◽  
Content Type ◽  
Staphylococcus Saprophyticus ◽  
Tract Infections

ABSTRACT Staphylococcus saprophyticus is an important cause of urinary tract infections (UTI) in women; such UTI are common, can be severe, and are associated with significant impacts to public health. In addition to being a cause of human UTI, S. saprophyticus can be found in the environment, in food, and associated with animals. After discovering that UTI strains of S. saprophyticus are for the most part closely related to each other, we sought to determine whether these strains are specially adapted to cause disease in humans. We found evidence suggesting that a mutation in the gene aas is advantageous in the context of human infection. We hypothesize that the mutation allows S. saprophyticus to survive better in the human urinary tract. These results show how bacteria found in the environment can evolve to cause disease. Human-pathogenic bacteria are found in a variety of niches, including free-living, zoonotic, and microbiome environments. Identifying bacterial adaptations that enable invasive disease is an important means of gaining insight into the molecular basis of pathogenesis and understanding pathogen emergence. Staphylococcus saprophyticus, a leading cause of urinary tract infections, can be found in the environment, food, animals, and the human microbiome. We identified a selective sweep in the gene encoding the Aas adhesin, a key virulence factor that binds host fibronectin. We hypothesize that the mutation under selection (aas_2206A>C) facilitates colonization of the urinary tract, an environment where bacteria are subject to strong shearing forces. The mutation appears to have enabled emergence and expansion of a human-pathogenic lineage of S. saprophyticus. These results demonstrate the power of evolutionary genomic approaches in discovering the genetic basis of virulence and emphasize the pleiotropy and adaptability of bacteria occupying diverse niches. IMPORTANCE Staphylococcus saprophyticus is an important cause of urinary tract infections (UTI) in women; such UTI are common, can be severe, and are associated with significant impacts to public health. In addition to being a cause of human UTI, S. saprophyticus can be found in the environment, in food, and associated with animals. After discovering that UTI strains of S. saprophyticus are for the most part closely related to each other, we sought to determine whether these strains are specially adapted to cause disease in humans. We found evidence suggesting that a mutation in the gene aas is advantageous in the context of human infection. We hypothesize that the mutation allows S. saprophyticus to survive better in the human urinary tract. These results show how bacteria found in the environment can evolve to cause disease.

scholarly journals Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrea Nuzzo ◽  
Stephanie Van Horn ◽  
Christopher Traini ◽  
Caroline R. Perry ◽  
Etienne F. Dumont ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Human Microbiome ◽  
Time Points ◽  
Pharyngeal Cavity ◽  
Adult Females ◽  
Microbiome Diversity ◽  
Antibiotic Drug ◽  
Tract Infections

Abstract Background With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov: NCT03568942). Results Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa. Conclusion Our findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery. Trial registration NCT03568942. Registered 26 June 2018.

scholarly journals Exploring the possibilities of infrared spectroscopy for urine sediment examination and detection of pathogenic bacteria in urinary tract infections

2020 ◽  
Vol 58 (10) ◽  
pp. 1759-1767
Author(s):  
Mieke Steenbeke ◽  
Sander De Bruyne ◽  
Jerina Boelens ◽  
Matthijs Oyaert ◽  
Griet Glorieux ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Pathogenic Bacteria ◽  
Agar Plate ◽  
Principal Component ◽  
Blood Agar Plate ◽  
Urine Sediment ◽  
Flight Mass Spectrometry ◽  
Tract Infections

AbstractObjectivesIn this study, the possibilities of Fourier-transformed infrared spectroscopy (FTIR) for analysis of urine sediments and for detection of bacteria causing urinary tract infections (UTIs) were investigated.MethodsDried urine specimens of control subjects and patients presenting with various nephrological and urological conditions were analysed using mid-infrared spectroscopy (4,000–400 cm−1). Urine samples from patients with a UTI were inoculated on a blood agar plate. After drying of the pure bacterial colonies, FTIR was applied and compared with the results obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chemometric data analysis was used to classify the different species.ResultsDue to the typical molecular assignments of lipids, proteins, nucleic acids and carbohydrates, FTIR was able to identify bacteria and showed promising results in the detection of proteins, lipids, white and red blood cells, as well as in the identification of crystals. Principal component analysis (PCA) allowed to differentiate between Gram-negative and Gram-positive species and soft independent modelling of class analogy (SIMCA) revealed promising classification ratios between the different pathogens.ConclusionsFTIR can be considered as a supplementary method for urine sediment examination and for detection of pathogenic bacteria in UTI.

Urinary tract infections in febrile children: Changing spectra of pathogenic bacteria and antibiotic susceptibilities?

2018 ◽  
Vol 55 (6) ◽  
pp. 680-689
Author(s):  
Jus Rakhra ◽  
Gabrielle Williams ◽  
Ben J Marais ◽  
Jonathan C Craig ◽  
Hasantha Gunasekera
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Pathogenic Bacteria ◽  
Antibiotic Susceptibilities ◽  
Tract Infections

scholarly journals Selective isolation and eradication of E. coli associated with urinary tract infections using anti-fimbrial modified magnetic reduced graphene oxide nanoheaters

2017 ◽  
Vol 5 (40) ◽  
pp. 8133-8142 ◽  
Author(s):  
Fatima Halouane ◽  
Roxana Jijie ◽  
Dalila Meziane ◽  
Chengnan Li ◽  
Santosh K. Singh ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Pathogenic Bacteria ◽  
Selective Isolation ◽  
E Coli ◽  
Reduced Graphene ◽  
Tract Infections ◽  
Efficient Elimination ◽  
Magnetic Reduced Graphene Oxide

The fast and efficient elimination of pathogenic bacteria from water, food or biological samples such as blood remains a challenging task.

scholarly journals Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

2016 ◽  
Vol 80 (2) ◽  
pp. 351-367 ◽  
Author(s):  
Amelia E. Barber ◽  
J. Paul Norton ◽  
Travis J. Wiles ◽  
Matthew A. Mulvey
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Bacterial Infections ◽  
Etiologic Agent ◽  
Human Infection ◽  
Model Systems ◽  
High Rate ◽  
Valuable Insight ◽  
Tract Infections ◽  
Insight Into

SUMMARYUrinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenicEscherichia coli(UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host.

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