Cognitive Deficits Found in a Pro-inflammatory State are Independent of ERK1/2 Signaling in the Murine Brain Hippocampus Treated with Shiga Toxin 2 from Enterohemorrhagic Escherichia coli.

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.

Phylogenetic group and virulence profile classification in Escherichia coli from distinct isolation sources in Mexico.

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.

Systemic Bacterial Infection in a Captive Agouti (Dasyprocta leporina Linnaeus, 1758).

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.

The transcriptional activator of the bfp operon in EPEC (PerA) interacts with the RNA polymerase alpha subunit.

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.

Epidemiology and associated microbiota changes in deployed military personnel at high risk of traveler's diarrhea.

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.

Pic-Producing Escherichia coli Induces High Production of Proinflammatory Mediators by the Host Leading to Death by Sepsis.

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.

Impact of Escherichia coli infection in broiler breeder chicks: The effect of oxidative stress on weight gain.

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 (n = 10 per group): an intraperitoneally-infected group (1 mL containing 1.5 × 108 CFU of E. coli) and a control group that received 1 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.

Coordinated transient interaction of ZO-1 and afadin is required for pedestal maturation induced by EspF from enteropathogenic Escherichia coli.

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.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice.

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.

Etiology and severity of diarrheal diseases in infants at the semiarid region of Brazil: A case-control study.

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.

Virulence-related genes are associated with clinical and nutritional outcomes of Shigella/Enteroinvasive Escherichia coli pathotype infection in children from Brazilian semiarid region: A community case-control study.

Shigella/Enteroinvasive Escherichia coli (EIEC) pathotype is a major enteropathogen associated with diarrhea and malnutrition in children from developing countries. This study aimed to correlate Shigella/EIEC virulence-related genes (VRGs) with clinical symptoms, nutritional status and coenteropathogens in children from the Brazilian semiarid region. We designed a case-control study of community diarrhea in six cities of the Brazil semiarid region with 1200 children aging 2-36 months. Standardized questionnaire was applied for collecting sociodemographic, nutritional status and clinical information of the children. DNA samples were extracted from stools and diagnosed for Shigella/EIEC using PCR-based approaches. Positive samples were tested for 28 VRGs using four multiplex PCRs. Intestinal inflammation was determined by measuring fecal myeloperoxidase (MPO). Shigella/EIEC pathotype was detected in 5% of the children and was significantly associated with diarrhea. The genes sen (encoding Shigella enterotoxin 2), ipgB2, ipgB1 (both encoding type 3 secretion system-T3SS effectors that modulate actin filament), and ospF (encoding a T3SS effector involved in suppression of host responses) were further associated with diarrhea in Shigella/EIEC positive children. Among children presenting diarrhea, virA gene (encoding a T3SS effector that promotes microtubule destabilization) was associated with fever, while virB (encoding a major transcriptional activator) was associated with low height-for-age z-score. In addition, these VRGs were associated with increased fecal MPO, and coinfection with Salmonella spp. was associated with increased abdominal pain. These data reinforce the impact of Shigella/EIEC on diarrhea in children from Brazilian semiarid region and highlighted the contributions of specific virulence genes for its pathobiology.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice

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.

Enterotoxigenic Escherichia coli infection promotes apoptosis in piglets.

Enterotoxigenic Escherichia coli (ETEC), as a universal pathogen, often causes diarrhea in animals and humans. However, whether ETEC infection induces apoptosis in host remains controversial. Herein, we use ETEC-infected piglet to investigate apoptosis in the jejunum. Apoptosis and the activation of capase-3 are observed in piglet jejunum after ETEC infection. Additionally, ETEC infection induces the activation of caspase-8 pathway, but inhibits the activation of caspase-9 pathway in piglet jejunum. These findings demonstrate that ETEC infection may inhibit the intrinsic pathway and activate the extrinsic pathway of apoptosis in piglets.

Enteroaggregative Escherichia coli subclinical and clinical infections.

PURPOSE OF REVIEW: The current review is to update the results on epidemiology, pathobiology, and genes related to virulence, clinical presentation, molecular diagnosis, antimicrobial resistance, and extraintestinal infection of enteroaggregative Escherichia coli (EAEC). RECENT FINDINGS: EAEC subclinical infection was significantly associated with reduced length at 2 years of age and EAEC and coinfections were associated with reduced delta weight-for-length and weight-for-age z-scores in the first 6 months of age in the MAL-ED birth cohort study. EAEC was associated with malnutrition in children 6-24 months of age in prospective case-control studies in Bangladesh and Brazil. Virulence gene-based studies have suggested aggregative fimbriae II may be a major contributor to disease, whereas AggR-activated regulator a marker of less severe disease. The high ability of EAEC colonization likely exacerbates effects of other microbial virulence strategies. Molecular diagnosis has been useful for understanding EAEC burden, although different criteria may relate to different pathogenic outcomes. SUMMARY: EAEC gained special interest in the past few years, especially due to association with growth decrements in children with subclinical infections and its important role as a copathogen. Understanding of EAEC pathogenesis advanced but further research is needed for elucidating both microbial and host factors influencing infection outcomes.

An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: cross-sectional study.

BACKGROUND: Uropathogenic Escherichia coli (UPEC) are one of the main bacteria causing urinary tract infections (UTIs). The rates of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically in recent years and could difficult the treatment. METHODS: The aim of the study was to determine multidrug-resistant bacteria, antibiotic resistance profile, virulence traits, and genetic background of 110 E. coli isolated from community (79 isolates) and hospital-acquired (31 isolates) urinary tract infections. The plasmid-mediated quinolone resistance genes presence was also investigated. A subset of 18 isolates with a quinolone-resistance phenotype was examined for common virulence genes encoded in diarrheagenic and extra-intestinal pathogenic E. coli by a specific E. coli microarray. RESULTS: Female children were the group most affected by UTIs, which were mainly community-acquired. Resistance to trimethoprim-sulfamethoxazole, ampicillin, and ampicillin-sulbactam was most prevalent. A frequent occurrence of resistance toward ciprofloxacin (47.3%), levofloxacin (43.6%) and cephalosporins (27.6%) was observed. In addition, 63% of the strains were multidrug-resistant (MDR). Almost all the fluoroquinolone (FQ)-resistant strains showed MDR-phenotype. Isolates from male patients were associated to FQ-resistant and MDR-phenotype. Moreover, hospital-acquired infections were correlated to third generation cephalosporin and nitrofurantoin resistance and the presence of kpsMTII gene. Overall, fimH (71.8%) and fyuA (68.2%), had the highest prevalence as virulence genes among isolates. However, the profile of virulence genes displayed a great diversity, which included the presence of genes related to diarrheagenic E. coli. Out of 110 isolates, 25 isolates (22.7%) were positive to qnrA, 23 (20.9%) to qnrB, 7 (6.4%) to qnrS1, 7 (6.4%) to aac(6')lb-cr, 5 (4.5%) to qnrD, and 1 (0.9%) to qnrC genes. A total of 12.7% of the isolates harbored blaCTX-M genes, with blaCTX-M-15 being the most prevalent. CONCLUSIONS: Urinary tract infection due to E. coli may be difficult to treat empirically due to high resistance to commonly used antibiotics. Continuous surveillance of multidrug resistant organisms and patterns of drug resistance are needed in order to prevent treatment failure and reduce selective pressure. These findings may help choosing more suitable treatments of UTI patients in this region of Mexico.

The Periplasmic Trehalase Affects Type 1 Fimbria Production and Virulence of Extraintestinal Pathogenic Escherichia coli Strain MT78.

Extraintestinal pathogenic Escherichia coli (ExPEC) is responsible for various infections outside the gastrointestinal tract in humans and other animals. ExPEC strain MT78 is invasive to various nonphagocytic cells and highly virulent in vivo To identify genes required for invasion of nonphagocytic cells by this strain, we applied signature-tagged mutagenesis to generate a library of mutants and tested them for invasion of avian fibroblasts. Mutants showing reduced cellular invasion included those with insertions in the fim operon, encoding type 1 fimbriae. Another attenuated mutant showed a disruption in the treA gene, which encodes a periplasmic trehalase. The substrate of TreA, trehalose, can be metabolized and used as a carbon source or can serve as an osmoprotectant under conditions of osmotic stress in E. coli K-12. We generated and characterized mutant MT78ΔtreA In contrast to the wild type, MT78ΔtreA was able to grow under osmotic stress caused by 0.6 M urea but not in minimal M9 medium with trehalose as the only carbon source. It presented decreased association and invasion of avian fibroblasts, decreased yeast agglutination titer, and impaired type 1 fimbria production. In a murine model of urinary tract infection, MT78ΔtreA was less able to colonize the bladder. All phenotypes were rescued in the complemented mutant. Our results show that the treA gene is needed for optimal production of type 1 fimbriae in ExPEC strain MT78 and that loss of treA significantly reduces its cell invasion capacity and colonization of the bladder in a murine model of urinary tract infection.

Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS).

Hemolytic uremic syndrome (HUS) is defined as a triad of noninmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The most frequent presentation is secondary to Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, which is termed postdiarrheal, epidemiologic or Stx-HUS, considering that Stx is the necessary etiological factor. After ingestion, STEC colonize the intestine and produce Stx, which translocates across the intestinal epithelium. Once Stx enters the bloodstream, it interacts with renal endothelial and epithelial cells, and leukocytes. This review summarizes the current evidence about the involvement of inflammatory components as central pathogenic factors that could determine outcome of STEC infections. Intestinal inflammation may favor epithelial leakage and subsequent passage of Stx to the systemic circulation. Vascular damage triggered by Stx promotes not only release of thrombin and increased fibrin concentration but also production of cytokines and chemokines by endothelial cells. Recent evidence from animal models and patients strongly indicate that several immune cells types may participate in HUS physiopathology: neutrophils, through release of proteases and reactive oxygen species (ROS); monocytes/macrophages through secretion of cytokines and chemokines. In addition, high levels of Bb factor and soluble C5b-9 (sC5b-9) in plasma as well as complement factors adhered to platelet-leukocyte complexes, microparticles and microvesicles, suggest activation of the alternative pathway of complement. Thus, acute immune response secondary to STEC infection, the Stx stimulatory effect on different immune cells, and inflammatory stimulus secondary to endothelial damage all together converge to define a strong inflammatory status that worsens Stx toxicity and disease.

Cathelicidin modulates synthesis of Toll-like Receptors (TLRs) 4 and 9 in colonic epithelium.

Cathelicidin are innate antimicrobial peptides with broad immunomodulatory functions; however, their role in regulating intestinal defenses is not well characterized. This study aimed to investigate the role of cathelicidin modulating expression of Toll-like receptors (TLRs) 4 and 9 in colonic epithelium in response to bacterial patterns. We demonstrated herein that intestinal epithelial cells, when primed by bacterial lipopolysaccharide (LPS), responded to cathelicidin by increased transcription and protein synthesis of TLR4. This cathelicidin-induced response required the interaction of LPS-TLR4 and activation of MAPK signalling pathways. However, cathelicidin blocked TLR9 responses induced by TLR9 ligand CpG oligodeoxynucleotide (CpG ODN) in these colonic epithelial cells. Modulations of TLRs triggered by cathelicidin in intestinal epithelium occurred mainly in the apical compartment of intestinal cells. Activation of TLR4 by ligands in combination with cathelicidin promoted CXCL8 chemokine secretion and epithelial antimicrobial defenses against Escherichia coli. We concluded that cathelicidin selectively modulated synthesis of TLR4 and 9 in intestinal epithelium, but only when cells were exposed to virulence factors, mostly from apical surfaces. Enhanced TLR4 expression promoted by cathelicidin in intestinal epithelium may be crucial for controlling enteric infectious diseases.

Distribution of serine protease autotransporters of Enterobacteriaceae in typical and atypical enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is an agent of acute and persistent diarrhea worldwide, categorized in typical or atypical subgroups. Some EAEC virulence factors are members of the serine protease autotransporters of Enterobacteriaceae (SPATE). The presence of SPATE-encoding genes of different E. coli pathotypes was searched in a large collection of EAEC strains, and a possible association between SPATEs and E. coli phylogroups was investigated. Among 108 typical and 85 atypical EAEC, pic was the most prevalent gene, detected in 47.1% of the strains, followed by sat (24.3%), espI (21.2%), pet (19.2%), sepA (13.5%), sigA (4.1%), eatA (4.1%), vat (1.0%), espP and tsh, detected in one strain (0.5%) each; while epeA and espC were not detected. Phylogenetic analysis demonstrated that 39.9% of the strains belonged to group A, 23.3% to B1, 10.9% to B2, 7.8% to D, 8.8% to E and 1.5% to F. The majority of the SPATE genes were distributed in typical and atypical strains without association with any phylogroup. In addition, pic and pet were strongly associated with typical EAEC and sepA was detected in close association with atypical EAEC. Our data indicate that SPATEs may represent important virulence traits in both subgroups of EAEC.

Colibacillosis in a New Zealand white rabbit (Oryctolagus cuniculus).

Colibacillosis is a disease caused by Escherichia coli in a variety of animals, including humans. Rabbit colibacillosis is infrequent or with an incipient description in Chile. Here, we describe an E. coli case in a white New Zealand rabbit at an animal facility in Santiago, Chile. Necropsy, histology, bacteriology, and 16S sequencing indicated an E. coli systemic infection. Phylogenetic analysis suggested that this E. coli J305 isolate is closely related to Shigella spp.