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In recent years, there has been an unprecedented advancement in in situ analytical approaches that contribute to the mechanistic understanding of microbial communities by explicitly incorporating ecology and studying their assembly. In this study, we have analyzed the temporal profiles of the healthy broiler cecal microbiome from day 3 to day 35 to recover the stable and varying components of microbial communities. During this period, the broilers were fed three different diets chronologically, and therefore, we have recovered signature microbial species that dominate during each dietary regime. Since broilers were raised in multiple pens, we have also parameterized these as an environmental condition to explore microbial niches and their overlap. All of these analyses were performed in view of different parameters such as body weight (BW-mean), feed intake (FI), feed conversion ratio (FCR), and age (days) to link them to a subset of microbes that these parameters have a bearing upon. We found that gut microbial communities exhibited strong and statistically significant specificity for several environmental variables. Through regression models, genera that positively/negatively correlate with the bird's age were identified. Some shortchain fatty acids (SCFAs)-producing bacteria, including Izemoplasmatales, Gastranaerophilales, and Roseburia, have a positive correlation with age. Certain pathogens, such as Escherichia-Shigella, Sporomusa, Campylobacter, and Enterococcus, negatively correlated with the bird's age, which indicated a high disease risk in the initial days. Moreover, the majority of pathways involved in amino acid biosynthesis were also positively correlated with the bird's age. Some probiotic genera associated with improved performance included Oscillospirales; UCG-010, Shuttleworthia, Bifidobacterium, and Butyricicoccaceae; UCG-009. In general, predicted antimicrobial resistance genes (piARGs) contributed at a stable level, but there was a slight increase in abundance when the diet was changed. To the best of the authors' knowledge, this is one of the first studies looking at the stability, complexity, and ecology of natural broiler microbiota development in a temporal setting. [ABSTRACT FROM AUTHOR]

Cytolethal distending toxin (CDT) is produced by a range of Gram-negative pathogenic bacteria such as Campylobacter jejuni. CDT represents an important virulence factor that is a heterotrimeric complex composed of CdtA, CdtB, and CdtC. CdtA and CdtC constitute regulatory subunits whilst CdtB acts as the catalytic subunit exhibiting phosphatase and DNase activities, resulting in cell cycle arrest and cell death. Extracellular vesicle (EV) secretion is an evolutionarily conserved process that is present throughout all kingdoms. Mammalian EVs play important roles in regular cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses. Here, we demonstrate that CDT targets the endo-lysosomal compartment, partially evading lysosomal degradation and exploiting unconventional secretion (EV release), which is largely involved in bacterial infections. CDT-like effects are transferred by Caco-2 cells to uninfected heterologous U937 and homologous Caco-2 cells. The journey of EVs derived from CDT-treated Caco-2 cells is associated with both intestinal and myeloid tumour cells. EV release represents the primary route of CDT dissemination, revealing an active toxin as part of the cargo. We demonstrated that bacterial toxins could represent suitable tools in cancer therapy, highlighting both the benefits and limitations. The global cell response involves a moderate induction of apoptosis and autophagic features may play a protective role against toxin-induced cell death. EVs from CDT-treated Caco-2 cells represent reliable CDT carriers, potentially suitable in colorectal cancer treatments. Our data present a potential bacterial-related biotherapeutic supporting a multidrug anticancer protocol. [ABSTRACT FROM AUTHOR]

Many neurotropic strains of Escherichia coli cause potentially lethal bacteraemia and meningitis in newborn infants by virtue of their capacity to elaborate the protective polysialic acid (polySia) K1 capsule. Recombinant capsule depolymerase, endosialidase E (endoE), selectively removes polySia from the bacterial surface; when administered intraperitoneally to infected neonatal rats, the enzyme interrupts the transit of E. coli K1 from gut to brain via the blood circulation and prevents death from systemic infection. We now show that experimental E. coli K1 infection is accompanied by extensive modulation of host gene expression in the liver, spleen and brain tissues of neonatal rats. Bacterial invasion of the brain resulted in a threefold or greater upregulation of approximately 400 genes, a large number of which were associated with the induction of inflammation and the immune and stress responses: these included genes encoding C-X-C and C-C chemokines, lipocalins, cytokines, apolipoproteins and enzymes involved in the synthesis of low-molecular-mass inflammatory mediators. Administration of a single dose of endoE, 24 h after initiation of systemic infection, markedly reduced, but did not completely abrogate, these changes in gene expression, suggesting that attenuation of E. coli K1 virulence by removal of the polySia capsule may minimize the attendant inflammatory processes that contribute to poor outcome in these severe systemic infections. DOI 10.1099/mic.0.036145-0

Campylobacter jejuni is the predominant cause of bacterial gastroenteritis worldwide, but traditional typing methods are unable to discriminate strains from different sources that cause disease in humans. We report the use of genomotyping (whole-genome comparisons of microbes using DNA microarrays) combined with Bayesian-based algorithms to model the phylogeny of this major food-borne pathogen. In this study 111 C. jejuni strains were examined by genomotyping isolates from humans with a spectrum of C. jejuni-associated disease (70 strains), chickens (17 strains), bovines (13 strains), ovines (5 strains), and the environment (6 strains). From these data, the Bayesian phylogeny of the isolates revealed two distinct clades unequivocally supported by Bayesian probabilities (P = 1); a livestock clade comprising 31/35 (88.6%) of the livestock isolates and a 'nonlivestock' clade comprising further clades of environmental isolates. Several genes were identified as characteristic of strains in the livestock clade. The most prominent was a cluster of six genes (cj1321 to cj1326) within the flagellin glycosylation locus, which were confirmed by PCR analysis as genetic markers in six additional chicken-associated strains. Surprisingly these studies show that the majority (39/70, 55.7%) of C. jejuni human isolates were found in the nonlivestock clade, suggesting that most C. jejuni infections may be from nonlivestock (and possibly nonagricultural) sources. This study has provided insight into a previously unidentified reservoir of C. jejuni infection that may have implications in disease-control strategies. The comparative phylogenomics approach described provides a robust methodological prototype that should be applicable to other microbes. microarray analysis | gastrointestinal pathogen | Bayesian-based algorithm