Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a "fishy" odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria

Emerging Insights into Antibiotic-Associated Diarrhea and Clostridium difficile Infection through the Lens of Microbial Ecology

Antibiotics are the main, and often only, clinical intervention for prophylactic and active treatment of bacterial infections in humans. Perhaps it is not surprising that these drugs also shift the composition of commensal bacteria inside our bodies, especially those within the gut microbial community (microbiota). How these dynamics ultimately affect the function of the gut microbiota, however, is not fully appreciated. Likewise, how antibiotic induced changes facilitate the outgrowth and pathogenicity of certain bacterial strains remains largely enigmatic. Here, we discuss the merits of a microbial ecology approach toward understanding a common side effect of antibiotic use, antibiotic-associated diarrhea (AAD), and the opportunistic bacterial infections that sometimes underlie it. As an example, we discuss how this approach is being used to address complex disease dynamics during Clostridium difficile infection

Clostridium difficile ribotype diversity at six health care institutions in the United States

Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart

Characterization of the cryptic Escherichia lineages: rapid identification and prevalence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86967/1/j.1462-2920.2011.02519.x.pd

Correlation between Tick Density and Pathogen Endemicity, New Hampshire

To assess the endemicity of tick-borne pathogens in New Hampshire, we surveyed adult tick vectors. Pathogens were more prevalent in areas of high tick density, suggesting a correlation between tick establishment and pathogen endemicity. Infection rates in ticks correlated with disease frequency in humans

Escherichia coli Isolates That Carry vat, fyuA, chuA, and yfcV Efficiently Colonize the Urinary Tract

Extraintestinal Escherichia coli (ExPEC), a heterogeneous group of pathogens, encompasses avian, neonatal meningitis, and uropathogenic E. coli strains. While several virulence factors are associated with ExPEC, there is no core set of virulence factors that can be used to definitively differentiate these pathotypes. Here we describe a multiplex of four virulence factor-encoding genes, yfcV, vat,fyuA, and chuA, highly associated with uropathogenic E. coli strains that can distinguish three groups of E. coli: diarrheagenic and animal-associated E. colistrains, human commensal and avian pathogenic E. coli strains, and uropathogenic and neonatal meningitis E. coli strains. Furthermore, human intestinal isolates that encode all four predictor genes express them during exponential growth in human urine and colonize the bladder in the mouse model of ascending urinary tract infection in higher numbers than human commensal strains that do not encode the four predictor genes (P = 0.02), suggesting that the presence of the predictors correlates with uropathogenic potential

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

Emergence of carbapenemase-producing Klebsiella pneumoniae of sequence type 258 in Michigan, USA

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in our hospital increased beginning in 2009. We aimed to study the clinical and molecular epidemiology of these emerging isolates. We performed a retrospective review of all adult patients with clinical cultures confirmed as CPE by positive modified Hodge test from 5/2009-5/2010 at the University of Michigan Health System (UMHS). Clinical information was obtained from electronic medical records. Available CPE isolates were analyzed by polymerase chain reaction (PCR) and sequencing of the 16S rRNA encoding gene and blaKPC locus. Multilocus sequence typing (MLST) was used to characterize Klebsiella pneumoniae isolates. Twenty six unique CPE isolates were obtained from 25 adult patients. The majority were Klebsiella pneumoniae (n=17). Other isolates included K. oxytoca (n=3), Citrobacter freundii (n=2), Enterobacter cloacae (n=2), Enterobacter aerogenes (n=1) and Escherichia coli (n=1). Molecular characterization of 19 available CPE isolates showed that 13 (68%) carried the KPC-3 allele and 6 (32%) carried the KPC-2 allele. Among 14 available K. pneumoniae strains, 12 (86%) carried the KPC-3 allele and belonged to a common lineage, sequence type (ST) 258. The other 2 (14%) K. pneumoniae isolates carried the KPC-2 allele and belonged to two unique STs. Among these ST 258 strains, 67% were isolated from patients with prior exposures to health care settings outside of our institution. In contrast, all CPE isolates carrying the KPC-2 allele and all non ST 258 CPE isolates had acquisition attributable to our hospital. Molecular epidemiology of carbapenemase producing K. pneumoniae suggests that KPC-3 producing K. pneumoniae isolates of a common lineage, sequence type (ST 258), are emerging in our hospital. While ST 258 is a dominant sequence type throughout the United States, this study is the first to report its presence in Michigan

Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus

Background: In a murine model of inflammatory bowel disease (IBD), treatment of colitis in IL-10 gene-deficient mice with the parasitic helminth Heligmosomoides polygyrus ameliorates colonic inflammation. The cellular and molecular mechanisms driving this therapeutic host response are being studied vigorously. One proposed mechanism is that H. polygyrus infection favors the outgrowth or suppression of certain bacteria, which in turn help modulate host immunity. Methods: To quantify the effect of H. polygyrus infection on the composition of the gastrointestinal (GI) tract microbiota, we conducted two independent microbial ecology analyses of C57BL/6 mice. We obtained and analyzed 3,353 bacterial 16S rRNA encoding gene sequences from the ileum and cecum of infected and uninfected mice as well as incective H. polygyrus larvae at the outset of the second experiment and adult worms taken directly from the mouse duodenum at the end of the second experiment. Results: We found that a significant shift in the abundance and relative distribution of bacterial species in the ileum of mice is associated with H. polygyrus infection. Members of the bacterial family Lactobacillaceae significantly increased in abundance in the ileum of infected mice reproducibly in two independent experiments despite having different microbiotas present at the outset of each experiment. Conclusions: These data support the concept that helminth infection shifts the composition of intestinal bacteria. The clinical consequences of these shifts in intestinal flora are yet to be explored. (Inflamm Bowel Dis 2010)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78230/1/21299_ftp.pd

458 Influence of a Gastrointestinal Infection on Lung Immunity

OBJECTIVES/GOALS: We aim to characterize how Heligmosomoides polygyrus bakeri (H. poly) alleviates murine allergic asthma which shares many characteristics of human asthma. This approach of has already identified helminth-produced human immune cell ligand “mimics” that hold great potential for next-generation clinical biologics METHODS/STUDY POPULATION: We examined the lung tissue of C57BL/6 mice infected with H. poly for changes in the pulmonary microenvironment. At ten days post infection, four infected mice and two co-housed uninfected mice were sacrificed, and their lung tissue harvested for examination of RNA via RT-qPCR. This design allows for the comparison between the lung microenvironments of infected and naīve mice. In future experiments, we intend to characterize what small molecules produced by the helminth drive changes in the lung using germ-free models of H. poly infection. RESULTS/ANTICIPATED RESULTS: We found key differences in lung chemokines between mice infected with H. poly and naīve mice. Using a student t-test with naīve correction for variance, we were able to show significant differences in the expression of E cadherin (p = 0.0355), CXCL10 (p = 0.0025), CX3CL1 (p = 0.0029), CCR2 (p = 0.017), and IDO1 (0.0078). We also found that differences in the expression of CCL5 bordered on significant with a p-value of 0.066. The expression of most of these markers (CXCL10, CCR2, CCL5, and IDO1) was elevated in the lungs of infected mice compared to naīve controls. In contrast, E cadherin and CX3CL1 showed the opposite trend with naīve mice showing greater expression. These clear differences in lung tissue gene expression underscore the connection between the gastrointestinal and pulmonary mucosal immune compartments. DISCUSSION/SIGNIFICANCE: The changes are unexpected for an infection that has been shown to attenuate allergic inflammation in the lung with increases in the IFN-Y responsive genes IDO1 and CXCL10 and inflammatory lung markers, CCL5 and CCR2. In contrast, there were decreases in inflammatory lung marker CX3CL1 and the tight junction protein E cadherin in infected mice