Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “virulence evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources

Typing of Yersinia pestis isolates from the state of Ceará, Brazil.

AIMS: To investigate whether modifications in Yersinia pestis isolates from three plague foci from the state of Ceará, Brazil, had occurred over the years as a consequence of genetic adaptation to the environment. METHODS AND RESULTS: The isolates were studied with respect to susceptibility to antimicrobial drugs, plasmid and protein profiling, pigmentation on Congo red-agar plates, and the presence of some pathogenicity genes using PCR. Most of the expected virulence markers were detected in the cultures examined. There was no evidence of any alteration that could be associated with their origin (patients, rodents and fleas) or period of isolation (1971-1997). CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Phenotypic or genotypic changes were not detected in the cultures examined. However, the results obtained will serve as a reference to follow the evolution of Y. pestis in these foci.

Animals↗

Type III effector diversification via both pathoadaptation and horizontal transfer in response to a coevolutionary arms race.

The concept of the coevolutionary arms race holds a central position in our understanding of pathogen-host interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and HopZ3) distributed among approximately 45% of the strains. All alleles were sequenced and their expression was confirmed. Evolutionary analyses determined that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged via pathoadaptive mutational changes into three functional and two degenerate forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal transfer from other ecologically similar bacteria. A PAML selection analysis revealed that the C terminus of HopZ1 is under strong positive selection. Despite the extensive genetic variation observed in this family, all three homologs have cysteine-protease activity, although their substrate specificity may vary. The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele. These data indicate that the P. syringae HopZ family has undergone allelic diversification via both pathoadaptive mutational changes and horizontal transfer in response to selection imposed by the host defense system. This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range.

Adaptation, Biological↗

Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans.

Our earlier findings established that cyclic AMP-dependent protein kinase functions in a signaling cascade that regulates mating and virulence of Cryptococcus neoformans var. grubii (serotype A). Mutants lacking the serotype A protein kinase A (PKA) catalytic subunit Pka1 are unable to mate, fail to produce melanin or capsule, and are avirulent in animal models, whereas mutants lacking the PKA regulatory subunit Pkr1 overproduce capsule and are hypervirulent. Because other mutations have been observed to confer different phenotypes in two diverged varieties of C. neoformans (grubii variety [serotype A] and neoformans variety [serotype D]), we analyzed the functions of the PKA genes in the serotype D neoformans variety. Surprisingly, the Pka1 catalytic subunit was not required for mating, haploid fruiting, or melanin or capsule production of serotype D strains. Here we identify a second PKA catalytic subunit gene, PKA2, that is present in both serotype A and D strains of C. neoformans. The divergent Pka2 catalytic subunit was found to regulate mating, haploid fruiting, and virulence factor production in serotype D strains. In contrast, Pka2 has no role in mating, melanin production, or capsule formation in serotype A strains. Our studies illustrate how different components of signaling pathways can be co-opted and functionally specialized during the evolution of related but distinct varieties or subspecies of a human fungal pathogen.

Alleles↗

Common themes in microbial pathogenicity.

A bacterial pathogen is a highly adapted microorganism which has the capacity to cause disease. The mechanisms used by pathogenic bacteria to cause infection and disease usually include an interactive group of virulence determinants, sometimes coregulated, which are suited for the interaction of a particular microorganism with a specific host. Because pathogens must overcome similar host barriers, common themes in microbial pathogenesis have evolved. However, these mechanisms are diverse between species and not necessarily conserved; instead, convergent evolution has developed several different mechanisms to overcome host barriers. The success of a bacterial pathogen can be measured by the degree with which it replicates after entering the host and reaching its specific niche. Successful microbial infection reflects persistence within a host and avoidance or neutralization of the specific and nonspecific defense mechanisms of the host. The degree of success of a pathogen is dependent upon the status of the host. As pathogens pass through a host, they are exposed to new environments. Highly adapted pathogenic organisms have developed biochemical sensors exquisitely designed to measure and respond to such environmental stimuli and accordingly to regulate a cascade of virulence determinants essential for life within the host. The pathogenic state is the product of dynamic selective pressures on microbial populations.

Animals↗

Differences in virulence between isolates of feline Sporotrichosis.

Sporotrichosis is a chronic subcutaneous mycosis caused by Sporothrix schenckii. This work aimed to evaluate the virulence of two different isolates of S. schenckii from cutaneous (CUT) and systemic (SYS) forms of feline sporotrichosis. A standard inoculum with 2 x 10(3) yeast cells/ml was prepared from each of the isolates. The experimental infection was carried out with 0.1 ml of the inoculum from both isolates and then injected in the paw pads of Swiss albino mice of groups CUT and SYS. The clinical evolution of the disease and the diameter of the lesion at the inoculated sites were evaluated during nine weeks. Four necropsies were done to collect material from the lesions (p < 0.01). Group CUT demonstrated a more evident clinical evolution of the disease from week two to week five; large lesions in the paw pad on week four (p < 0.01); and a higher incidence of lesions in other parts of the body (p < 0.01) than group SYS (p < 0.01). S. schenckii was isolated from the inoculated site in groups SYS and CUT until days 30 and 45, respectively. Granulomas with yeast cells usually localized in the central area were observed in histopathology sections on days 15 and 30 post-inoculations. Those yeast cells decreased on day 45 being absent on day 62 when tissue repair initiated. The results showed that distinct clinical isolates of S. schenckii cause significant differences in the clinical evolution of sporotrichosis.

Animals↗

A baseline model for the apparent competition between many host strains: the evolution of host resistance to microparasites.

The purpose of this article is to establish and analyse a baseline model for the apparent competition between many host strains attempting to avoid a uniform microparasitic population. The model is formulated and analysed using invasion criteria in the main text. The results are verified by more formal methods in the appendix. Cases in which the microparasite can invade are distinguished geometrically from those in which it cannot using threshold and strain composition conditions. A major result obtained when the pathogen persists is a competitive exclusion principle for host resistance. For non-lethal infections, the winning strain is that which affords the pathogen maximum threshold density; for possibly lethal infections, a somewhat generalized version of this criterion is presented and discussed. The tension is highlighted between these results and the baseline behaviour of many pathogen strains and a uniform host population-here the winning pathogen strain is that with minimum threshold density.

Animals↗

Pheromone-inducible conjugation in Enterococcus faecalis: a model for the evolution of biological complexity?

Pheromone-inducible transfer of the plasmid pCF10 in Enterococcus faecalis is regulated using a complicated network of proteins and RNAs. The plasmid itself has been assembled from parts garnered from a variety of sources, and many aspects of the system resemble a biological kluge. Recently several new functions of various pCF10 gene products that participate in regulation of plasmid transfer have been identified. The results indicate that selective pressures controlling the evolution of the plasmid have produced a highly complex regulatory network with multiple biological functions that may serve well as a model for the evolution of biological complexity.

Bacterial Proteins↗

Eukaryotic genes in Mycobacterium tuberculosis could have a role in pathogenesis and immunomodulation.

Acquisition of new genetic material through horizontal gene transfer has been an important feature in the evolution of many pathogenic bacteria. Here, we report the presence of 19 genes of eukaryotic origin in the genome of Mycobacterium tuberculosis, some of which are unique to the M. tuberculosis complex. These genes, having been retained in the genome through selective advantage, most probably have key functions in the organism and in mammalian tuberculosis. We explore the role these genes might have in manipulation of the host immune system by altering the balance of steroid hormones.

Amino Acid Sequence↗

The Yersinia high-pathogenicity island: an iron-uptake island.

Highly pathogenic Yersinia carry a pathogenicity island termed high-pathogenicity island (HPI). The Yersinia HPI comprises genes involved in the synthesis of the siderophore yersiniabactin and can thus be regarded as an iron-uptake island. A unique characteristic of the HPI is its wide distribution among different enterobacteria such as Escherichia coli, Klebsiella, Citrobacter and Salmonella. Other types of iron-uptake systems are also carried by different pathogenicity islands in enterobacteria.

Animals↗

Rapid cell variation can determine the establishment of a persistent viral infection.

Evidence for a mechanism of initiation of viral persistence in which the cell, and not the virus, plays a critical role has been obtained using the important animal pathogen foot-and-mouth disease virus (FMDV). We have developed a virulence assay consisting of quantification of the ability of virus to kill cells and of cells to divide in the presence of virus and to initiate a carrier state. Cells were cured of FMDV at early times following a cytolytic infection of BHK-21 monolayers with FMDV. When cured cells were subjected to the virulence assay they showed an increased ability to survive a second infection by FMDV but not by other RNA viruses. This altered phenotype was maintained as a stable genetic trait. When the virus present in such early surviving cells was used to infect BHK-21 cells, it proved to be as virulent as the initial cytolytic FMDV and, furthermore, its ability to kill BHK-21 cells increased upon replication in the surviving cells. Both the level of genetic heterogeneity and the rate of evolution of FMDV were similar to those previously documented during acute and persistent FMDV infections. The results suggest that, in contrast to most other viral systems, the critical element in the establishment of a persistent infection of BHK-21 cells with FMDV is the ability of the host cells to vary genetically and phenotypically, which promotes selection of cells with increased resistance to virus. The possible relevance of this mechanism to viral persistence in vivo is discussed.

Animals↗

Describing ancient horizontal gene transfers at the nucleotide and gene levels by comparative pathogenicity island genometrics.

MOTIVATION: Lateral gene transfer is a major mechanism contributing to bacterial genome dynamics and pathovar emergence via pathogenicity island (PAI) spreading. However, since few of these genomic exchanges are experimentally reproducible, it is difficult to establish evolutionary scenarios for the successive PAI transmissions between bacterial genera. Methods initially developed at the gene and/or nucleotide level for genomics, i.e. comparisons of concatenated sequences, ortholog frequency, gene order or dinucleotide usage, were combined and applied here to homologous PAIs: we call this approach comparative PAI genometrics. RESULTS: YAPI, a Yersinia PAI, and related islands were compared with measure evolutionary relationships between related modules. Through use of our genometric approach designed for tracking codon usage adaptation and gene phylogeny, an ancient inter-genus PAI transfer was oriented for the first time by characterizing the genomic environment in which the ancestral island emerged and its subsequent transfers to other bacterial genera.

Chromosome Mapping↗

Intimate interactions of enteropathogenic Escherichia coli at the host cell surface.

Unlike many gastrointestinal pathogens, enteropathogenic Escherichia coli orchestrates the modulation of host cellular and immune responses from the exterior of the infected cell, chiefly via the secreted and translocated components of a type III secretion system. Close inspection of these enteropathogenic Escherichia coli proteins and the interactions they mediate provides an increasingly coherent picture of the pathogenic mechanisms that enteropathogenic Escherichia coli uses to exploit its host.

Adhesins, Bacterial↗

Pseudogene accumulation might promote the adaptive microevolution of Yersinia pestis.

Plague is a natural focus-based disease, and for better understanding of this disease it is crucial to determine the molecular mechanisms of its pathogen, Yersinia pestis, for adapting to different foci. Gene inactivation, loss and acquisition are the main mechanisms that contribute to a pathogen's fitness. Determination of the whole-genome sequences of three Y. pestis strains, CO92, KIM and 91001, provided a good opportunity to probe into its genome in minute detail. Many genetic variations were found between the three strains. The present work focused on adaptive microevolutionary analysis of Y. pestis from different natural plague foci in China based on pseudogene profiles. Twenty-four mutations that led to inactivation in the corresponding genes were analysed, and a PCR-based screening method was employed to investigate the distribution of these mutations among Y. pestis isolates from different foci and also among seven strains of Yersinia pseudotuberculosis. It was found that Y. pestis isolates from the same focus had identical mutation profiles, and 260 isolates of Y. pestis were divided into eight genotypes, while Y. pseudotuberculosis harboured wild-type alleles for all the mutations. The isolates of three known biovars were grouped into distinct branches in the phylogenetic tree, which supports the proposition that biovars mediaevalis and orientalis directly arose from biovar antiqua individually. The constructed phylogenetic tree suggests that the isolates from focus B should be the oldest lineage of Y. pestis in China except for isolates from foci L and M, which might be a special lineage of Y. pestis and originated differently to the others.

Adaptation, Physiological↗

Evolutionary relationships in the genus Bordetella.

The nucleotide sequence of the pertussis toxin operon of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica, has shown that the last two species contain many common mutations and are likely to derive from a common ancestor (Aricò and Rappuoli, 1987). To elucidate further the evolutionary relationships between the Bordetella species, we have cloned and sequenced the promoter region and the gene coding for the S1 subunit of pertussis toxin from additional B. pertussis strains, such as the type strain BP 18323 and two recent clinical isolates, namely strain BP 13456 from Sweden and strain BP SA1 from Italy. While the strains BP SA1 and BP 13456 are shown to differ from the published B. pertussis sequences by only one base pair, the type strain BP 18323 contains a total of 11 base-pair substitutions. Remarkably, 9 of the 11 substitutions found in BP 18323 are also common to B. parapertussis and B. bronchiseptica, strongly suggesting that this strain derives from the same ancestor as B. parapertussis and B. bronchiseptica. Computer analysis of the sequence data allows the construction of an evolutionary 'tree' showing that the B. pertussis strains are very homogeneous and significantly distant from B. parapertussis and B. bronchiseptica. Therefore the proposed conversion from B. parapertussis to B. pertussis appears highly improbable.

Amino Acid Sequence↗

Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of extraintestinal pathogenic Escherichia coli.

Type 1 fimbriae of Escherichia coli mediate mannose-specific adhesion to host epithelial surfaces and consist of a major, antigenically variable pilin subunit, FimA, and a minor, structurally conserved adhesive subunit, FimH, located on the fimbrial tip. We have analysed the variability of fimA and fimH in strains of vaginal and other origin that belong to one of the most prominent clonal groups of extraintestinal pathogenic E. coli, comprised of O1:K1-, O2:K1- and O18:K1-based serotypes. Multiple locus sequence typing (MLST) of this group revealed that the strains have identical (at all but one nucleotide position) eight housekeeping loci around the genome and belong to the ST95 complex defined by the publicly available E. coli MLST database. Multiple highly diverse fimA alleles have been introduced into the ST95 clonal complex via horizontal transfer, at a frequency comparable to that of genes defining the major O- and H-antigens. However, no further significant FimA diversification has occurred via point mutation after the transfers. In contrast, while fimH alleles also move horizontally (along with the fimA loci), they acquire point amino acid replacements at a higher rate than either housekeeping genes or fimA. These FimH mutations enhance binding to monomannose receptors and bacterial tropism for human vaginal epithelium. A similar pattern of rapid within-clonal structural evolution of the adhesive, but not pilin, subunit is also seen, respectively, in papG and papA alleles of the di-galactose-specific P-fimbriae. Thus, while structurally diverse pilin subunits of E. coli fimbriae are under selective pressure for frequent horizontal transfer between clones, the adhesive subunits of extraintestinal E. coli are under strong positive selection (Dn/Ds > 1 for fimH and papG) for functionally adaptive amino acid replacements.

Adhesins, Escherichia coli↗