Pathogenic species in the Yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. The advent of large-scale population genomic ...studies has greatly accelerated the progress in this field, and Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. In this Review, we highlight the gene gain, gene loss and genome rearrangement events that have been identified by genomic studies in pathogenic Yersinia species, and we discuss how these findings are changing our understanding of pathogen evolution. Finally, as these traits are also found in the genomes of other species in the Enterobacteriaceae, we suggest that they provide a blueprint for the evolution of enteropathogenic bacteria.
The predation and engulfment of bacteria by
facilitates intimate interactions between host and prey. This process plays an important and underestimated role in the physiology, ecology and evolution ...of pathogenic bacteria.
species can be reservoirs for many important human pathogens including
is the leading cause of bacterial foodborne enteritis worldwide, despite being a microaerophile that is incapable of withstanding atmospheric levels of oxygen long-term. The persistence and transmission of this major pathogen in the natural environment outside its avian and mammalian hosts is not fully understood. Recent evidence has provided insight into the relationship of
and
spp. where
are a transient host for this pathogen. Mutations to the flagella components were shown to affect
interactions. Here, we show that the motility function of flagella is not a prerequisite for
interactions and that specific
-linked glycan modifications of the
major flagellin, FlaA, are important for the recognition, interaction and phagocytosis by
. Substitution of the
-linked glycosylated serine 415 and threonine 477 with alanine within FlaA abolished
interactions with
and these mutants were indistinguishable from a Δ
mutant. By contrast, mutation to serine 405 did not affect
11168H and
interactions. Given the abundance of flagella glycosylation among clinically important pathogens, our observations may have a wider implication for understanding host-pathogen interactions.
The ubiquitous unicellular eukaryote,
, is known to play a role in the survival and dissemination of
is the leading cause of bacterial foodborne gastroenteritis world-wide and is a major public ...health problem. The ability of
to interact and potentially invade epithelial cells is thought to be key for disease development in humans. We examined
grown under standard laboratory conditions, 11168H
with that harvested from within
(11168H
) or
(11168H
), and compared their ability to invade different cell lines.
harvested from within amoebae had a ~3.7-fold increase in invasiveness into T84 human epithelial cells and a striking ~11-fold increase for re-entry into
cells. We also investigated the invasiveness and survivability of six diverse representative
strains within
spp., our results confirm that invasion and survivability is likely host-cell-dependent. Our survival assay data led us to conclude that
spp. are a transient host for
and that survival within amoebae pre-adapts
and enhances subsequent cell invasion. This study provides new insight into
interactions with amoebae and its increased invasiveness potential in mammalian hosts.
is considered to be the most common bacterial cause of human gastroenteritis worldwide.
can cause bloody diarrhoea, fever and abdominal pain in humans along with post-infectious sequelae such as ...Guillain-Barré syndrome (a paralytic autoimmune complication).
infections can be fatal, particularly among young children.
are distributed in most warm-blooded animals, and therefore the main route of transmission is generally foodborne, via the consumption and handling of meat products (particularly poultry).
is microaerophilic and oxygen-sensitive, although it appears to be omnipresent in the environment, one of the many contradictions of
.
Glycoconjugate vaccines against bacteria are one of the success stories of modern medicine and have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. ...Glycoconjugate vaccines are produced by covalently linking a bacterial polysaccharide (usually capsule, or more recently O-antigen), to a carrier protein. Given the success of glycoconjugate vaccines, it is surprising that to date only vaccines against
type b,
and
have been fully licenced. This is set to change through the glycoengineering of recombinant vaccines in bacteria, such as
, that act as mini factories for the production of an inexhaustible and renewable supply of pure vaccine product. The recombinant process, termed Protein Glycan Coupling Technology (PGCT) or bioconjugation, offers a low-cost option for the production of pure glycoconjugate vaccines, with the in-built flexibility of adding different glycan/protein combinations for custom made vaccines. Numerous vaccine candidates have now been made using PGCT, which include those improving existing licenced vaccines (e.g., pneumococcal), entirely new vaccines for both Gram-positive and Gram-negative bacteria, and (because of the low production costs) veterinary pathogens. Given the continued threat of antimicrobial resistance and the potential peril of bioterrorist agents, the production of new glycoconjugate vaccines against old and new bacterial foes is particularly timely. In this review, we will outline the component parts of bacterial PGCT, including recent advances, the advantages and limitations of the technology, and future applications and perspectives.
Next-generation sequencing has ushered in a new era of microbial genomics, enabling the detailed historical and geographical tracing of bacteria. This is helping to shape our understanding of ...bacterial evolution.
Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with ...broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.
Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international ...emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies.
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