RESUMO
Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) produces hemorrhagic colitis, hemolytic uremic syndrome (HUS), and acute encephalopathy. The mortality rate in HUS increases significantly when the central nervous system (CNS) is involved. Besides, EHEC also releases lipopolysaccharide (LPS). Many reports have described cognitive dysfunctions in HUS patients, the hippocampus being one of the brain areas targeted by EHEC infection. In this context, a translational murine model of encephalopathy was employed to establish the deleterious effects of Stx2 and the contribution of LPS in the hippocampus. The purpose of this work is to elucidate the signaling pathways that may activate the inflammatory processes triggered by Stx2, which produces cognitive alterations at the level of the hippocampus. Results demonstrate that Stx2 produced depression-like behavior, pro-inflammatory cytokine release, and NF-kB activation independent of the ERK1/2 signaling pathway, while co-administration of Stx2 and LPS reduced memory index. On the other hand, LPS activated NF-kB dependent on ERK1/2 signaling pathway. Cotreatment of Stx2 with LPS aggravated the pathologic state, while dexamethasone treatment succeeded in preventing behavioral alterations. Our present work suggests that the use of drugs such as corticosteroids or NF-kB signaling inhibitors may serve as neuroprotectors from EHEC infection.
Assuntos
Encefalopatias , Disfunção Cognitiva , Escherichia coli Êntero-Hemorrágica , Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Camundongos , Humanos , Animais , Toxina Shiga II/toxicidade , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , NF-kappa B , Encéfalo/patologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/patologia , Hipocampo/patologia , CogniçãoRESUMO
Escherichia coli is a leading cause of human enteric diseases worldwide. The rapid and accurate causal agent identification to a particular source represents a crucial step in the establishment of safety and health measures in the affected human populations and would thus provide insights into the relationship of traits that may contribute for pathogen persistence in a particular reservoir. The objective of the present study was to characterize over two hundred E. coli strains from different isolation sources in Mexico by conducting a correspondence analysis to explore associations with the detected phylogenetic groups. The results indicated that E. coli strains, recovered from distinct sources in Mexico, were classified into phylogroups B1 (35.8%), A (27.8%), and D (12.3%) and were clustered to particular clades according to the predicted phylogroups. The results from correspondence analysis showed that E. coli populations from distinct sources in Mexico, belonging to different phylogroups, were not dispersed randomly and were associated with a particular isolation source. Phylogroup A was strongly associated with human sources, and the phylogroup B1 showed a significant relationship with food sources. Additionally, phylogroup D was also related to human sources. Phylogroup B2 was associated with herbivorous and omnivorous mammals. Moreover, common virulence genes in the examined E. coli strains, assigned to all phylogroups, were identified as essential markers for survival and invasion in the host. Although virulence profiles varied among the detected phylogroups, E. coli strains belonging to phylogroup D, associated with humans, were found to contain the largest virulence gene repertoire conferring for persistence and survival in the host. In summary, these findings provide fundamental information for a better characterization of pathogenic E. coli, recovered from distinct isolation sources in Mexico and would assist in the development of better tools for identifying potential transmission routes of contamination.
Assuntos
Infecções por Escherichia coli , Escherichia coli , Animais , Humanos , Filogenia , Virulência/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/patologia , Fatores de Virulência/genética , MamíferosRESUMO
The agouti (Dasyprocta leporina) is a neotropical rodent which has the potential to be domesticated. As such, some research studies have been done on the biology of this animal. Recently, these animals are being kept in captivity as a source of animal protein. Animals which are kept in captivity may present diseases that would not have been reported in the wild due to lack of observation or the lack of occurrence. The aim of this short communication is to report a case of systemic bacterial infection that affected the lungs and liver of a captive agouti. Bacterial analysis revealed that the infection was caused by Escherichia coli. Bacterial infections have been reported in the mammary tissue as well as the skin of the agouti, but to the authors' knowledge, this is the first report of systemic infection in the agouti affecting several organs. This case was seen in a nine-month-old male agouti that was being housed at the University of the West Indies Field Station (UWI, UFS). The animal showed no apparent sign of disease except for lethargy and subsequently died before any treatment was administered. These findings showed that the agouti may have been under some stress (nutritional or environmental) which predisposed this animal to this infection. Future work has to address the nutritional requirements for the growing agouti as well as some treatment options for managements of similar cases in the future.
Assuntos
Dasyproctidae/microbiologia , Infecções por Escherichia coli/veterinária , Animais , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/patologia , Evolução Fatal , Hepatopatias/microbiologia , Hepatopatias/patologia , Hepatopatias/veterinária , Pneumopatias/microbiologia , Pneumopatias/patologia , Pneumopatias/veterinária , Masculino , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/patologia , Dermatopatias Bacterianas/veterináriaRESUMO
Enteropathogenic E. coli virulence genes are under the control of various regulators, one of which is PerA, an AraC/XylS-like regulator. PerA directly promotes its own expression and that of the bfp operon encoding the genes involved in the biogenesis of the bundle-forming pilus (BFP); it also activates PerC expression, which in turn stimulates locus of enterocyte effacement (LEE) activation through the LEE-encoded regulator Ler. Monomeric PerA directly binds to the per and bfp regulatory regions; however, it is not known whether interactions between PerA and the RNA polymerase (RNAP) are needed to activate gene transcription as has been observed for other AraC-like regulators. Results showed that PerA interacts with the alpha subunit of the RNAP polymerase and that it is necessary for the genetic and phenotypic expression of bfpA. Furthermore, an in silico analysis shows that PerA might be interacting with specific alpha subunit amino acids residues highlighting the direction of future experiments.
Assuntos
RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli Enteropatogênica/genética , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/genética , Proteínas Repressoras/metabolismo , RNA Polimerases Dirigidas por DNA/química , Escherichia coli Enteropatogênica/isolamento & purificação , Escherichia coli Enteropatogênica/metabolismo , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Óperon , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Virulência/genéticaRESUMO
Travelers' diarrhea (TD) is the most prevalent illness encountered by deployed military personnel and has a major impact on military operations, from reduced job performance to lost duty days. Frequently, the etiology of TD is unknown and, with underreporting of cases, it is difficult to accurately assess its impact. An increasing number of ailments include an altered or aberrant gut microbiome. To better understand the relationships between long-term deployments and TD, we studied military personnel during two nine-month deployment cycles in 2015-2016 to Honduras. To collect data on the prevalence of diarrhea and impact on duty, a total of 1173 personnel completed questionnaires at the end of their deployment. 56.7% reported reduced performance and 21.1% reported lost duty days. We conducted a passive surveillance study of all cases of diarrhea reporting to the medical unit with 152 total cases and a similar pattern of etiology. Enteroaggregative E. coli (EAEC, 52/152), enterotoxigenic E. coli (ETEC, 50/152), and enteropathogenic E. coli (EPEC, 35/152) were the most prevalent pathogens detected. An active longitudinal surveillance of 67 subjects also identified diarrheagenic E. coli as the primary etiology (7/16 EPEC, 7/16 EAEC, and 6/16 ETEC). Eleven subjects were recruited into a nested longitudinal substudy to examine gut microbiome changes associated with deployment. A 16S rRNA amplicon survey of fecal samples showed differentially abundant baseline taxa for subjects who contracted TD versus those who did not, as well as detection of taxa positively associated with self-reported gastrointestinal distress. Disrupted microbiota was also qualitatively observable for weeks preceding and following the incidents of TD. These findings illustrate the complex etiology of diarrhea amongst military personnel in deployed settings and its impacts on job performance. Potential factors of resistance or susceptibility can provide a foundation for future clinical trials to evaluate prevention and treatment strategies.
Assuntos
Diarreia/epidemiologia , Disenteria/epidemiologia , Escherichia coli Enteropatogênica/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Adulto , Diarreia/genética , Diarreia/microbiologia , Disenteria/genética , Disenteria/microbiologia , Disenteria/patologia , Escherichia coli Enteropatogênica/genética , Escherichia coli Enteropatogênica/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Honduras/epidemiologia , Humanos , Masculino , Militares , RNA Ribossômico 16S/genética , Fatores de Risco , Viagem , Doença Relacionada a ViagensRESUMO
Escherichia coli is an important pathogen responsible for a variety of diseases. We have recently shown that Pic, a serine protease secreted by E. coli, mediates immune evasion by the direct cleavage of complement molecules. The aim of this study was to investigate the action of a Pic-producing bacteria in a murine model of sepsis. Mice were infected with Pic-producing E. coli (F5) or F5∆pic mutant. Animal survival was monitored for five days, and a subset of mice was euthanized after 12 h for sample acquisition. The inoculation of Pic-producing bacteria induced 100% death within 24 h. The colony forming units count in the organs was significantly higher in F5. Hematological analysis showed a decrease of total leukocytes. Nitric oxide and cytokines were detected in serum, as well as on peritoneal lavage of the F5 group in higher levels than those detected in the other groups. In addition, immunophenotyping showed a decrease of activated lymphocytes and macrophages in the F5 group. Therefore, Pic represents an important virulence factor, allowing the survival of the bacterium in the bloodstream and several organs, as well as inducing a high production of proinflammatory mediators by the host, and concomitantly a cellular immunosuppression, leading to sepsis and death.
Assuntos
Citocinas/metabolismo , Infecções por Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Sepse/metabolismo , Serina Endopeptidases/metabolismo , Animais , Citocinas/genética , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/genética , Feminino , Inflamação/genética , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Camundongos , Sepse/genética , Sepse/microbiologia , Sepse/patologia , Serina Endopeptidases/genéticaRESUMO
The aim of this study was to determine whether oxidative stress occurs in Escherichia coli-infected broiler breeder chicks, as well as the impact of this infection on bird growth. Twenty birds, 25-day-old female birds were divided into two groups (nâ¯=â¯10 per group): an intraperitoneally-infected group (1â¯mL containing 1.5â¯×â¯108â¯CFU of E. coli) and a control group that received 1â¯mL of culture medium (uninfected birds). Birds were weighed individually at the beginning and at the end of the experiment, and samples were collected on days 0, 5 and 10 post-infection (PI). No clinical signs were observed throughout the experimental period; nevertheless, on day 10 PI, there was lower growth and weight gain in infected birds than in the control group. The infected birds showed pericarditis and liver congestion, as well as moderate periportal inflammatory infiltrates with predominance of neutrophils. Significantly higher numbers of total leukocytes, lymphocytes, heterophils and monocytes were observed in the infected group on days 5 and 10 PI, as well as significantly higher total protein and globulin levels; albumin values significantly decreased over the same period. Levels of serum oxidative biomarkers (lipid peroxidation (TBARS) and free radicals (ROS)) were significantly higher at 10 PI, as was glutathione S-transferase (GST) activity during the same period. Hepatic ROS and protein thiol levels were significantly higher in E. coli-infected birds, as well as activities of the antioxidant enzymes catalase, superoxide dismutase. In the spleen, only GST activity was significantly higher for the infected group, unlike the brain, where SOD activity, ROS and non-protein thiol levels were significantly higher in infected birds than in the control group. These data suggested that colibacillosis causes oxidative stress in broiler breeder chicks, negatively affecting their weight gain.
Assuntos
Infecções por Escherichia coli/metabolismo , Estresse Oxidativo/fisiologia , Doenças das Aves Domésticas/metabolismo , Aumento de Peso/fisiologia , Animais , Antioxidantes/análise , Biomarcadores/sangue , Encéfalo/metabolismo , Encéfalo/patologia , Catalase/sangue , Galinhas , Escherichia coli , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/patologia , Feminino , Radicais Livres , Glutationa Transferase/sangue , Peroxidação de Lipídeos , Fígado/metabolismo , Fígado/patologia , Doenças das Aves Domésticas/sangue , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/patologia , Baço/metabolismo , Baço/patologia , Superóxido Dismutase , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Enteropathogenic Escherichia coli (EPEC) infection causes a histopathological lesion including recruitment of F-actin beneath the attached bacteria and formation of actin-rich pedestal-like structures. Another important target of EPEC is the tight junction (TJ), and EspF induces displacement of TJ proteins and increased intestinal permeability. Previously, we determined that an EPEC strain lacking EspF did not cause TJ disruption; meanwhile, pedestals were located on the TJ and smaller than those induced by the wild-type strain. Therefore, EspF could be playing an important role in both phenotypes. Here, using different cell models, we found that EspF was essential for pedestal maturation through ZO-1 disassembly from TJ, leading to (a) ZO-1 recruitment to the pedestal structure; no other main TJ proteins were required. Recruited ZO-1 allowed the afadin recruitment. (b) Afadin recruitment caused an afadin-ZO-1 transient interaction, like during TJ formation. (c) Afadin and ZO-1 were segregated to the tip and the stem of pedestal, respectively, causing pedestal maturation. Initiation of these three discrete phases for pedestal maturation functionally and physically required EspF expression. Pedestal maturation process could help coordinate the epithelial actomyosin function by maintaining the actin-rich column composing the pedestal structure and could be important in the dynamics of the pedestal movement on epithelial cells.
Assuntos
Escherichia coli Enteropatogênica/fisiologia , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/genética , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Actinas/metabolismo , Células Epiteliais/metabolismo , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/metabolismo , Imunofluorescência , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Permeabilidade , Fosfoproteínas/metabolismo , Ligação ProteicaRESUMO
BACKGROUND: Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. METHODS: Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. RESULT: In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. CONCLUSION: Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.
Assuntos
Infecções por Escherichia coli/patologia , Mutação/genética , Lesões Pré-Cancerosas/genética , Prostatite/genética , Animais , Doença Crônica , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Prostatite/microbiologia , Prostatite/patologiaRESUMO
BACKGROUND: Diarrheal diseases are an important cause of morbidity and mortality among children in developing countries. We aimed to study the etiology and severity of diarrhea in children living in the low-income semiarid region of Brazil. METHODOLOGY: This is a cross-sectional, age-matched case-control study of diarrhea in children aged 2-36 months from six cities in Brazil's semiarid region. Clinical, epidemiological, and anthropometric data were matched with fecal samples collected for the identification of enteropathogens. RESULTS: We enrolled 1,200 children, 596 cases and 604 controls. By univariate analysis, eight enteropathogens were associated with diarrhea: Norovirus GII (OR 5.08, 95% CI 2.10, 12.30), Adenovirus (OR 3.79, 95% CI 1.41, 10.23), typical enteropathogenic Escherichia coli (tEPEC), (OR 3.28, 95% CI 1.39, 7.73), enterotoxigenic E. coli (ETEC LT and ST producing toxins), (OR 2.58, 95% CI 0.99, 6.69), rotavirus (OR 1.91, 95% CI 1.20, 3.02), shiga toxin-producing E. coli (STEC; OR 1.77, 95% CI 1.16, 2.69), enteroaggregative E. coli (EAEC), (OR 1.45, 95% CI 1.16, 1.83) and Giardia spp. (OR 1.39, 95% CI 1.05, 1.84). By logistic regression of all enteropathogens, the best predictors of diarrhea were norovirus, adenovirus, rotavirus, STEC, Giardia spp. and EAEC. A high diarrhea severity score was associated with EAEC. CONCLUSIONS: Six enteropathogens: Norovirus, Adenovirus, Rotavirus, STEC, Giardia spp., and EAEC were associated with diarrhea in children from Brazil's semiarid region. EAEC was associated with increased diarrhea severity.