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Frontiers in Cellular and Infection... 2022The genera and were independently described in 1885. These Gram-negative rods colonize the human intestinal tract regarded as the main reservoir of these opportunistic... (Review)
Review
The genera and were independently described in 1885. These Gram-negative rods colonize the human intestinal tract regarded as the main reservoir of these opportunistic pathogens. In favorable conditions they cause infections, often hospital-acquired ones. The activity of and , the leading pathogens within each genus, results in infections of the urinary (UTIs) and respiratory tracts, wounds, bacteremia, affecting mainly immunocompromised patients. and cause polymicrobial UTIs, which are often persistent due to the catheter biofilm formation or increasing resistance of the bacteria to antibiotics. In this situation a need arises to find the antigens with features common to both species. Among many virulence factors produced by both pathogens urease shows some structural similarities but the biggest similarities have been observed in lipids A and the core regions of lipopolysaccharides (LPSs). Both species produce capsular polysaccharides (CPSs) but only in these antigens play a crucial role in the serological classification scheme, which in spp. is based on the structural and serological diversity of LPS O-polysaccharides (OPSs). Structural and serological similarities observed for spp. and spp. polysaccharides are important in the search for the cross-reacting vaccine antigens.
Topics: Humans; Proteus mirabilis; Klebsiella pneumoniae; Virulence Factors; Coinfection; Urinary Tract Infections; Lipopolysaccharides
PubMed: 36339335
DOI: 10.3389/fcimb.2022.991657 -
MSystems Aug 2023is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike...
is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike other Gram-negative bacteria, may not exhibit significant intraspecies variation in gene content. However, there has not been a comprehensive analysis of large numbers of genomes from various sources to support or refute this hypothesis. We performed comparative genomic analysis on 2,060 genomes. We sequenced the genomes of 893 isolates recovered from clinical specimens from three large US academic medical centers, combined with 1,006 genomes from NCBI Assembly and 161 genomes assembled from Illumina reads in the public domain. We used average nucleotide identity (ANI) to delineate species and subspecies, core genome phylogenetic analysis to identify clusters of highly related genomes, and pan-genome annotation to identify genes of interest not present in the model strain HI4320. Within our cohort, is composed of 10 named species and 5 uncharacterized genomospecies. can be subdivided into three subspecies; subspecies 1 represented 96.7% (1,822/1,883) of all genomes. The pan-genome includes 15,399 genes outside of HI4320, and 34.3% (5,282/15,399) of these genes have no putative assigned function. Subspecies 1 is composed of several highly related clonal groups. Prophages and gene clusters encoding putatively extracellular-facing proteins are associated with clonal groups. Uncharacterized genes not present in the model strain HI4320 but with homology to known virulence-associated operons can be identified within the pan-genome. IMPORTANCE Gram-negative bacteria use a variety of extracellular facing factors to interact with eukaryotic hosts. Due to intraspecies genetic variability, these factors may not be present in the model strain for a given organism, potentially providing incomplete understanding of host-microbial interactions. In contrast to previous reports on , but similar to other Gram-negative bacteria, has a mosaic genome with a linkage between phylogenetic position and accessory genome content. encodes a variety of genes that may impact host-microbe dynamics beyond what is represented in the model strain HI4320. The diverse, whole-genome characterized strain bank from this work can be used in conjunction with reverse genetic and infection models to better understand the impact of accessory genome content on bacterial physiology and pathogenesis of infection.
Topics: Humans; Proteus mirabilis; Proteomics; Phylogeny; Virulence; Virulence Factors
PubMed: 37341494
DOI: 10.1128/msystems.00159-23 -
Cold Spring Harbor Molecular Case... Jun 2020Proteus syndrome is a mosaic disorder that can cause progressive postnatal overgrowth of nearly any organ or tissue. To date, Proteus syndrome has been exclusively...
Proteus syndrome is a mosaic disorder that can cause progressive postnatal overgrowth of nearly any organ or tissue. To date, Proteus syndrome has been exclusively associated with the mosaic c.49G > A p.(Glu17Lys) pathogenic variant in , a variant that is also present in many cancers. Here we describe an individual with severe Proteus syndrome who died at 7.5 yr of age from combined parenchymal and restrictive pulmonary disease. Remarkably, this individual was found to harbor a mosaic c.49_50delinsAG p.(Glu17Arg) variant in at a variant allele fraction that ranged from <0.01 to 0.46 in fibroblasts established from an overgrown digit. This variant was demonstrated to be constitutively activating by phosphorylation of AKT(S473). These data document allelic heterogeneity for Proteus syndrome. We recommend that individuals with a potential clinical diagnosis of Proteus syndrome who are negative for the p.(Glu17Lys) variant be tested for other variants in .
Topics: Alleles; Allelic Imbalance; Amino Acid Substitution; Cervical Vertebrae; Genetic Association Studies; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetic Testing; Humans; Infant; Magnetic Resonance Imaging; Male; Medical History Taking; Mutation; Phenotype; Proteus Syndrome; Proto-Oncogene Proteins c-akt; Radiography; Symptom Assessment
PubMed: 32327430
DOI: 10.1101/mcs.a005181 -
The Pan African Medical Journal 2017Acute septic arthritis is rare. It is associated with poor prognosis in terms of mortality and morbidity. We report the case of a 61-year old patient with spontaneous... (Review)
Review
Acute septic arthritis is rare. It is associated with poor prognosis in terms of mortality and morbidity. We report the case of a 61-year old patient with spontaneous Proteus mirabilis septic arthritis. He suffered from complicated diabetes associated with positive blood cultures and synovial fluid cultures. Patient's evolution was favorable thanks to early diagnosis and initiation of adequate antibiotic therapy. Proteus mirabilis septic arthritis is rare. On that basis we conducted a literature review of cases of Proteus mirabilis pyogenic arthritis to highlight the risk factors, pathogenesis, treatment and evolution of these diseases. Diagnosis is commonly based on microbiological analysis, early articular puncture biopsy is performed before the initiation of antibiotic treatment, direct examination, culture and antibiogram which are useful as guidance for antibiotic therapy. Septic arthritis is a diagnostic and therapeutic emergency; early management of this disease allows total healing without after-effects.
Topics: Acute Disease; Anti-Bacterial Agents; Arthritis, Infectious; Humans; Male; Middle Aged; Prognosis; Proteus Infections; Proteus mirabilis; Risk Factors; Synovial Fluid
PubMed: 28674590
DOI: 10.11604/pamj.2017.26.197.12271 -
Frontiers in Cellular and Infection... 2022The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the...
The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast and the Gram-negative bacterium resulting in enhanced host cell damage. This synergistic effect was conserved across different isolates and occurred also with non- species and mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between and is induced by contact, but also by soluble factors. Specifically, we identified -mediated glucose consumption and farnesol production as potential triggers for virulence. In summary, our study demonstrates that coinfection of enterocytes with and can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination.
Topics: Candida; Candida albicans; Coinfection; Enterocytes; Humans; Proteus mirabilis
PubMed: 35651758
DOI: 10.3389/fcimb.2022.866416 -
Urologia Internationalis 2021Proteus mirabilis (PM) is a Gram-negative rod-shaped bacterium and widely exists in the natural environment, and it is most noted for its swarming motility and urease... (Review)
Review
Proteus mirabilis (PM) is a Gram-negative rod-shaped bacterium and widely exists in the natural environment, and it is most noted for its swarming motility and urease activity. PM is the main pathogen causing complicated urinary tract infections (UTIs), especially catheter-associated urinary tract infections. Clinically, PM can form a crystalline biofilm on the outer surface and inner cavity of the urethral indwelling catheter owing to its ureolytic biomineralization. This leads to catheter encrustation and blockage and, in most cases, is accompanied by urine retention and ascending UTI, causing cystitis, pyelonephritis, and the development of bladder or kidney stones, or even fatal complications such as septicemia and endotoxic shock. In this review, we discuss how PM is mediated by a catheter into the urethra, bladder, and then rose to the kidney causing UTI and the main virulence factors associated with different stages of infection, including flagella, pili or adhesins, urease, hemolysin, metal intake, and immune escape, encompassing both historical perspectives and current advances.
Topics: Catheter-Related Infections; Humans; Proteus Infections; Proteus mirabilis; Urinary Catheters; Urinary Tract Infections
PubMed: 33691318
DOI: 10.1159/000514097 -
Medicina (Kaunas, Lithuania) Feb 2022: and are related genera of opportunistic pathogens belonging to the family, often a cause of infections in the immunocompromised hosts, such as diabetic patients.... (Observational Study)
Observational Study
: and are related genera of opportunistic pathogens belonging to the family, often a cause of infections in the immunocompromised hosts, such as diabetic patients. Their clinical significance has increased due to their intrinsic resistance to polymyxins, which is often associated with acquired resistance mechanisms. In this study we evaluated the infections caused by and in two groups of patients, with diabetes (group 1) and without diabetes (group 2) admitted to the intensive care unit and surgical wards. The infections were investigated in terms of infection type, risk factors, clinical course, predictive factors for unfavourable outcomes and antibiotic resistance profile. : An observational, retrospective, cross-sectional study was conducted, comprising all patients infected with these pathogens. Bacterial identification and antibiotic sensitivity testing were performed using the Vitek2C automated system. : Comparison of the two groups showed that the statistically significant common infectious risk factors were found less frequently among diabetic patients when compared with non-diabetic patients, and that antimicrobial resistance was significantly lower in the diabetic patient group. However, survival rates did not differ between the two groups, drawing attention to the implications of diabetes as comorbidity. Additionally, with regard to the antibiotic resistance profile, 38.89% of strains isolated from diabetic patients belonged to the difficult-to-treat (DTR) phenotype, contributing to the severity of these infections compared with those caused by , of which 32% were wild type strains and 0% were DTR phenotype. The DTR/extended spectrum beta-lactamase producing isolates more than doubled the risk of mortality, while the presence of nasogastric nutrition tripled the risk. : infections that occurred in diabetic patients proved to be more difficult to treat, the majority of them being healthcare-associated bacteremias.
Topics: Cross-Sectional Studies; Diabetes Mellitus; Enterobacteriaceae Infections; Humans; Proteus Infections; Proteus mirabilis; Providencia; Retrospective Studies
PubMed: 35208593
DOI: 10.3390/medicina58020271 -
Clinical Trials (London, England) Jun 2022The assessment of patient-reported outcomes in clinical trials has enormous potential to promote patient-centred care, but for this potential to be realized, the...
BACKGROUND
The assessment of patient-reported outcomes in clinical trials has enormous potential to promote patient-centred care, but for this potential to be realized, the patient-reported outcomes must be captured effectively and communicated clearly. Over the past decade, methodologic tools have been developed to inform the design, analysis, reporting, and interpretation of patient-reported outcome data from clinical trials. We formed the PROTEUS-Trials Consortium (Patient-Reported Outcomes Tools: Engaging Users and Stakeholders) to disseminate and implement these methodologic tools.
METHODS
PROTEUS-Trials are engaging with patient, clinician, research, and regulatory stakeholders from 27 organizations in the United States, Canada, Australia, the United Kingdom, and Europe to develop both organization-specific and cross-cutting strategies for implementing and disseminating the methodologic tools. Guided by the Knowledge-to-Action framework, we conducted consortium-wide webinars and meetings, as well as individual calls with participating organizations, to develop a workplan, which we are currently executing.
RESULTS
Six methodologic tools serve as the foundation for PROTEUS-Trials dissemination and implementation efforts: the Standard Protocol Items: Recommendations for Interventional Trials-patient-reported outcome extension for writing protocols with patient-reported outcomes, the International Society for Quality of Life Research Minimum Standards for selecting a patient-reported outcome measure, Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium recommendations for patient-reported outcome data analysis, the Consolidated Standards for Reporting of Trials-patient-reported outcome extension for reporting clinical trials with patient-reported outcomes, recommendations for the graphic display of patient-reported outcome data, and a Clinician's Checklist for reading and using an article about patient-reported outcomes. The PROTEUS-Trials website (www.TheProteusConsortium.org) serves as a central repository for the methodologic tools and associated resources. To date, we have developed (1) a roadmap to visually display where each of the six methodologic tools applies along the clinical trial trajectory, (2) web tutorials that provide guidance on the methodologic tools at different levels of detail, (3) checklists to provide brief summaries of each tool's recommendations, (4) a handbook to provide a self-guided approach to learning about the tools and recommendations, and (5) publications that address key topics related to patient-reported outcomes in clinical trials. We are also conducting organization-specific activities, including meetings, presentations, workshops, and webinars to publicize the existence of the methodologic tools and the PROTEUS-Trials resources. Work to develop communications strategies to ensure that PROTEUS-Trials reach key audiences with relevant information about patient-reported outcomes in clinical trials and PROTEUS-Trials is ongoing.
DISCUSSION
The PROTEUS-Trials Consortium aims to help researchers generate patient-reported outcome data from clinical trials to (1) enable investigators, regulators, and policy-makers to take the patient perspective into account when conducting research and making decisions; (2) help patients understand treatment options and make treatment decisions; and (3) inform clinicians' discussions with patients regarding treatment options. In these ways, the PROTEUS Consortium promotes patient-centred research and care.
Topics: Clinical Trials as Topic; Decision Making; Humans; Patient Reported Outcome Measures; Proteus; Quality of Life; Research Design; United States
PubMed: 35094586
DOI: 10.1177/17407745221077691 -
Mediators of Inflammation 2020Cancer causes a major health concern worldwide due to high incidence and mortality rates. To accomplish this purpose, the Scopus, PubMed, and Web of Science databases... (Review)
Review
Cancer causes a major health concern worldwide due to high incidence and mortality rates. To accomplish this purpose, the Scopus, PubMed, and Web of Science databases were searched using the keywords bacteria and cancer. Most of published research addressed several different factors that induced cancer, such as toxins, medications, smoking, and obesity. Nonetheless, few studies are dealing with cancer induction via bacterial infection. In addition, mechanisms of cancer induction via bacterial infections are not well understood. Therefore, in this review, we will shed light on different bacteria that induced cancer via different molecular mechanisms. Among the bacterial infection that induced cancer, was the first recognized bacteria which caused gastric cancer and might be also linked to extragastric cancer in humans. has been associated with adenocarcinoma in the distal stomach by its ability to cause severe inflammations. It has been found that inflammations induced cancer via different mechanisms including induction of cell proliferation and production of high levels of free radicals. Recently, free radicals were found to induce and cause various types of cancer. has been found to be associated with gallbladder carcinoma (GBC). Also, intercellular infection of lungs with Chlamydia pneumoniae was found to contribute as one of the ethological factors of lung cancer. Moreover, infection of the urinary tract with , spp., and has been found to cause bladder cancer. These microorganisms produce a high level of N-nitrosamines which are metabolically activated leading to the generation of alkylating agents that damage DNA and other macromolecules. It is concluded that a certain bacterium is linked with induction of a specific type of cancer via different molecular and biochemical mechanisms as discussed in the text in details. This infection could potentially affect human health in different ways. In addition, it is important to know the possible factors involved in cancer induction for better treatment of cancer patients.
Topics: Gallbladder Neoplasms; Helicobacter pylori; Humans; Incidence; Proteus mirabilis; Salmonella typhi; Staphylococcus aureus; Urinary Bladder Neoplasms
PubMed: 32724295
DOI: 10.1155/2020/4070419 -
Veterinary Medicine and Science Nov 2022Pyoderma is a purulent skin infection usually caused by bacteria and can be divided into primary and secondary categories based on histology. In the present study, an...
Pyoderma is a purulent skin infection usually caused by bacteria and can be divided into primary and secondary categories based on histology. In the present study, an 18-month-old female mixed breed sheep was examined for pyoderma at the injection site of the enterotoxemia vaccine. After routine bacteriology and histopathology procedures, secondary pyoderma caused by Proteus mirabilis was diagnosed. The bacterium analysed using genome sequencing and new strain called AJJ 2021 was diagnosed. This is the first report of pyoderma caused by Proteus mirabilis in sheep.
Topics: Female; Sheep; Animals; Proteus mirabilis; Pyoderma; Sheep Diseases
PubMed: 36049140
DOI: 10.1002/vms3.926