Anti-Whole Serum polyclonal antibody

Although enteroaggregativeE.coli(EAEC) has been implicated as a common cause of diarrhea in multiple settings, neither its essential genomic nature nor its role as an enteric pathogen are fully understood. The current definition of this pathotype requires demonstration of cellular adherence; a working molecular definition encompassesE.coliwhich do not harbor the heat-stable or heat-labile toxins of enterotoxigenicE.coli(ETEC) and harbor the genesaaiC,aggR, and/oraatA. In an effort to improve the definition of this pathotype, we report the most definitive characterization of the pan-genome of EAEC to date, applying comparative genomics and functional characterization on a collection of 97 EAEC strains isolated in the course of a multicenter case-control diarrhea study (Global Enteric Multi-Center Study, GEMS). Genomic analysis revealed that the EAEC strains mapped to all phylogenomic groups ofE.coli. Circa 70% of strains harbored one of the five described AAF variants; there were no additional AAF variants identified, and strains that lacked an identifiable AAF generally did not have an otherwise complete AggR regulon. An exception was strains that harbored an ETEC colonization factor (CF) CS22, like AAF a member of the chaperone-usher family of adhesins, but not phylogenetically related to the AAF family. Of all genes scored,sepAyielded the strongest association with diarrhea (P= 0.002) followed by the increased serum survival gene,iss(p = 0.026), and the outer membrane protease geneompT(p = 0.046). Notably, the EAEC genomes harbored several genes characteristically associated with otherE.colipathotypes. Our data suggest that a molecular definition of EAEC could compriseE.colistrains harboring AggR and a complete AAF(I-V) or CS22 gene cluster. Further, it is possible that strains meeting this definition could be both enteric bacteria and urinary/systemic pathogens. Author summary EnteroaggregativeE.coli(EAEC) has been implicated as a common cause of diarrhea in multiple settings and associated with linear growth faltering among children in low-income countries. Unlike otherE.colipathotypes EAEC stands alone in employing a phenotypic, rather than genotypic, definition. Therefore, the lack of a formally recognized genetic definition for EAEC serves to complicate its epidemiologic investigation. In an effort to improve the definition of this pathotype, we generated the most definitive characterization of the pan-genome of EAEC by performing whole genome sequencing on a collection of strains isolated from different geographic settings. We identified a genetic signature of EAEC which could comprise ofE.colistrains harboring the EAEC transcriptional activator and its adhesin dependent factors. Further, we found that EAEC strains harbor additional putative virulence genes previously reported in extraintestinal pathogenicE.coli(ExPEC) and, therefore, strains meeting the re-definition could be both enteric bacteria and urinary/systemic pathogens.

Despite pre-clinical evidence for the role of inflammation in traumatic brain injury (TBI), there is limited data on inflammatory biomarkers in mild TBI (mTBI). In this study, we describe the profile of plasma inflammatory cytokines and explore associations between these cytokines and neuropsychological outcomes after mTBI. Patients with mTBI with negative computed tomography and orthopedic injury (OI) controls without mTBI were prospectively recruited from emergency rooms at three trauma centers. Plasma inflammatory cytokine levels were measured from venous whole-blood samples that were collected at enrollment (within 24 h of injury) and at 6 months after injury. Neuropsychological tests were performed at 1 week, 1 month, 3 months, and 6 months after the injury. Multivariate regression analysis was performed to identify associations between inflammatory cytokines and neuropsychological outcomes. A total of 53 mTBI and 24 OI controls were included in this study. The majority of patients were male (62.3%), and injured in motor vehicle accidents (37.7%). Plasma interleukin (IL)-2 (p = 0.01) and IL-6 (p = 0.01) within 24 h post-injury were significantly higher for mTBI patients compared with OI controls. Elevated plasma IL-2 at 24 h was associated with more severe 1-week post-concussive symptoms (p = 0.001). At 6 months, elevated plasma IL-10 was associated with greater depression scores (p = 0.004) and more severe post-traumatic stress disorder (PTSD) symptoms (p = 0.001). Plasma cytokine levels (within 24 h and at 6 months post-injury) were significantly associated with early and late post-concussive symptoms, PTSD, and depression scores after mTBI. These results highlight the potential role of inflammation in the pathophysiology of post-traumatic symptoms after mTBI.