Genomic characterisation of an endometrial pathogenic Escherichia coli strain reveals the acquisition of genetic elements associated with extra-intestinal pathogenicity

BackgroundStrains of Escherichia coli cause a wide variety of intestinal and extra-intestinal diseases in both humans and animals, and are also often found in healthy individuals or the environment. Broadly, a strong phylogenetic relationship exists that distinguishes most E. coli causing intestinal disease from those that cause extra-intestinal disease, however, isolates within a recently described subclass of Extra-Intestinal Pathogenic E. coli (ExPEC), termed endometrial pathogenic E. coli, tend to be phylogenetically distant from the vast majority of characterised ExPECs, and more closely related to human intestinal pathogens. In this work, we investigate the genetic basis for ExPEC infection in the prototypic endometrial pathogenic E. coli strain MS499. ResultsBy investigating the genome of MS499 in comparison with a range of other E. coli sequences, we have discovered that this bacterium has acquired substantial lengths of DNA which encode factors more usually associated with ExPECs and less frequently found in the phylogroup relatives of MS499. Many of these acquired factors, including several iron acquisition systems and a virulence plasmid similar to that found in several ExPECs such as APEC O1 and the neonatal meningitis E. coli S88, play characterised roles in a variety of typical ExPEC infections and appear to have been acquired recently by the evolutionary lineage leading to MS499. ConclusionsTaking advantage of the phylogenetic relationship we describe between MS499 and several other closely related E. coli isolates from across the globe, we propose a step-wise evolution of a novel clade of sequence type 453 ExPECs within phylogroup B1, involving the recruitment of ExPEC virulence factors into the genome of an ancestrally non-extraintestinal E. coli, which has repurposed this lineage with the capacity to cause extraintestinal disease. These data reveal the genetic components which may be involved in this phenotype switching, and argue that horizontal gene exchange may be a key factor in the emergence of novel lineages of ExPECs

Naive Realism about Operators

A source of much difficulty and confusion in the interpretation of quantum mechanics is a ``naive realism about operators.'' By this we refer to various ways of taking too seriously the notion of operator-as-observable, and in particular to the all too casual talk about ``measuring operators'' that occurs when the subject is quantum mechanics. Without a specification of what should be meant by ``measuring'' a quantum observable, such an expression can have no clear meaning. A definite specification is provided by Bohmian mechanics, a theory that emerges from Sch\"rodinger's equation for a system of particles when we merely insist that ``particles'' means particles. Bohmian mechanics clarifies the status and the role of operators as observables in quantum mechanics by providing the operational details absent from standard quantum mechanics. It thereby allows us to readily dismiss all the radical claims traditionally enveloping the transition from the classical to the quantum realm---for example, that we must abandon classical logic or classical probability. The moral is rather simple: Beware naive realism, especially about operators!Comment: 18 pages, LaTex2e with AMS-LaTeX, to appear in Erkenntnis, 1996 (the proceedings of the international conference ``Probability, Dynamics and Causality,'' Luino, Italy, 15-17 June 1995, a special issue edited by D. Costantini and M.C. Gallavotti and dedicated to Prof. R. Jeffrey

The endometrial transcriptomic response to pregnancy is altered in cows after uterine infection

Pregnancy induces changes in the transcriptome of the bovine endometrium from 15 days after insemination. However, pregnancy is less likely to occur if cows had a postpartum bacterial infection of the uterus, even after the resolution of disease. We hypothesized that uterine bacterial infection alters the endometrial transcriptomic signature of pregnancy after the resolution of disease. To examine the endometrial transcriptomic signature of pregnancy, cows were inseminated 130 days after intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes, subsequently endometrium was collected 16 days after insemination for RNA sequencing. We found 171 pregnancy regulated genes in cows 146 days after bacterial infection. When comparing our findings with previous studies that described the endometrial transcriptomic signature of pregnancy in healthy cows, 24 genes were consistently differentially expressed in pregnancy, including MX1, MX2 and STAT1. However, 12 pregnancy regulated genes were found only in the endometrium of healthy cows, including ISG15 and TRANK1. Furthermore, 28 pregnancy regulated genes were found only in the endometrium of cows following bacterial infection and these were associated with altered iNOS, TLR, and IL-7 signaling pathways. Although 94 predicted upstream regulators were conserved amongst the studies, 14 were found only in the endometrium of pregnant healthy cows, and 5 were found only in cows following bacterial infection, including AIRE, NFKBIA, and DUSP1. In conclusion, there were both consistent and discordant features of the endometrial transcriptomic signature of pregnancy 146 days after intrauterine bacterial infusion. These findings imply that there is an essential transcriptomic signature of pregnancy, but that infection induces long-term changes in the endometrium that affect the transcriptomic response to pregnancy

Lipopolysaccharide alters CEBPβ signaling and reduces estradiol production in bovine granulosa cells

BackgroundBacterial infection of the uterus in postpartum dairy cows limits ovarian follicle growth, reduces blood estradiol concentrations, and leads to accumulation of bacterial lipopolysaccharide (LPS) in ovarian follicular fluid. Although treating granulosa cells with LPS in vitro decreases the expression of the estradiol synthesis enzyme CYP19A1 and reduces estradiol secretion, the molecular mechanisms are unclear. The transcription factor CCAAT enhancer binding protein beta (CEBPβ) not only facilitates the transcription of LPS regulated cytokines, but also binds to the promoter region of CYP19A1 in humans, mice, and buffalo. We hypothesized that LPS alters CEBPβ signaling to reduce CYP19A1 expression, resulting in decreased estradiol secretion.MethodsBovine granulosa cells were isolated from small/medium or large follicles and treated with LPS in the presence of FSH and androstenedione for up to 24 h.ResultsTreatment with LPS increased CXCL8 and IL6 gene expression and reduced estradiol secretion in granulosa cells from both small/medium and large follicles. However, LPS only reduced CYP19A1 expression in granulosa cells from large follicles. Treatment with LPS increased CEBPB expression and reduced CEBPβ nuclear localization in granulosa cells from small/medium follicles, but not granulosa cells from large follicles.ConclusionsAlthough LPS reduces estradiol synthesis in bovine granulosa cells, the effects of LPS on CYP19A1 and CEBPβ are dependent on follicle size