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Characterization of effector proteins translocated via the SPI1 type III secretion system of Salmonella typhimurium.

Salmonella spp. employ a conserved type III secretion system encoded within the pathogenicity island 1 (SPI1; centisome 63) to translocate effector proteins into the host cytosol. The translocated effector proteins trigger diverse responses including bacterial internalization. In a mutation analysis we have defined the set of effector proteins mediating tissue culture cell invasion. This set includes sopE2 (centisome 40-42), sopB (SPI5, centisome 20) and in the case of S. typhimurium SL1344 also the phage-encoded effector sopE (SopEphi, centisome 59-60). A triple mutant SL1344 derivative deficient of SopE, SopE2 and SopB was more than 100-fold attenuated in tissue culture cell invasion. Phylogenetic analyses indicate that the last common ancestor of all contemporary Salmonella lineages already harbored all genes necessary for host cell invasion, namely the SPI1 type III secretion system, sopE2 and sopB. SopE, which is 70% identical to sopE2 is only present in some Salmonella strains and emerged later well after the divergence of the contemporary Salmonella lineages. Interestingly, S. typhimurium strains that harbor sopE are associated with epidemics, arguing that sopE is one of the factors determining the "fitness" of a strain. We found that SopE can specifically activate a different set of host cellular RhoGTPases than SopE2. This allows the bacteria to fine tune host cellular responses very precisely and may offer an explanation for the improved epidemic fitness of sopE-positive S. typhimurium strains.

Animals↗

Intracellular life.

Intracellular parasites and endosymbionts are present in almost all forms of life, including bacteria. Some eukaryotic organelles are believed to be derived from ancestral endosymbionts. Parasites and symbionts show several adaptations to intracellular life. A comparative analysis of their biology suggests some general considerations involved in adapting to intracellular life and reveals a number of independently achieved strategies for the exploitation of an intracellular habitat. Symbioses mainly based on a form of syntrophy may have led to the establishment of unique physiological systems. Generally, a symbiont can be considered to be an attenuated pathogen. The combination of morphological studies, molecular phylogenetic analyses, and palaeobiological data has led to considerable improvement in the understanding of intracellular life evolution. Comparing host and symbiont phylogenies could lead to an explanation of the evolutionary history of symbiosis. These studies also provide strong evidences for the endosymbiogenesis of the eukaryotic cell. Indeed, an eubacterial origin for mitochondria and plastids is well accepted and is suggested for other organelles. The expansion of intracellular living associations is presented, with a particular emphasis on peculiar aspects and/or recent data, providing a global evaluation.

Animals↗

Genome plasticity and ori-ter rebalancing in Salmonella typhi.

Genome plasticity resulting from frequent rearrangement of the bacterial genome is a fascinating but poorly understood phenomenon. First reported in Salmonella typhi, it has been observed only in a small number of Salmonella serovars, although the over 2,500 known Salmonella serovars are all very closely related. To gain insights into this phenomenon and elucidate its roles in bacterial evolution, especially those involved in the formation of particular pathogens, we systematically analyzed the genomes of 127 wild-type S. typhi strains isolated from many places of the world and compared them with the two sequenced strains, Ty2 and CT18, attempting to find possible associations between genome rearrangement and other significant genomic features. Like other host-adapted Salmonella serovars, S. typhi contained large genome insertions, including the 134 kb Salmonella pathogenicity island, SPI7. Our analyses showed that SPI7 disrupted the physical balance of the bacterial genome between the replication origin (ori) and terminus (ter) when this DNA segment was inserted into the genome, and rearrangement in individual strains further changed the genome balance status, with a general tendency toward a better balanced genome structure. In a given S. typhi strain, genome diversification occurred and resulted in different structures among cells in the culture. Under a stressed condition, bacterial cells with better balanced genome structures were selected to greatly increase in proportion; in such cases, bacteria with better balanced genomes formed larger colonies and grew with shorter generation times. Our results support the hypothesis that genome plasticity as a result of frequent rearrangement provides the opportunity for the bacterial genome to adopt a better balanced structure and thus eventually stabilizes the genome during evolution.

Evolution, Molecular↗

Pathogen adaptation under imperfect vaccination: implications for pertussis.

Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity.

Adaptation, Biological↗

The first filamentous fungal genome sequences: Aspergillus leads the way for essential everyday resources or dusty museum specimens?

The published Aspergillus genome sequences (A. nidulans, A. fumigatus, A. oryzae) and further sequence data from A. clavatus, Neosartorya fischeri, A. flavus, A. niger, A. parasiticus and A. terreus are the first from a group of related filamentous fungi. They indicate the gains possible from genomic approaches, but also problems that arise after the sequences are finished. Benefits include a greater understanding of genome structure and evolution, insights into gene regulation, predictions of new factors that may be relevant to pathogenicity and the discovery of novel enzymes with biotechnological value. Areas where further developments are needed include gene and structure-function predictions, methods for comparative genome analysis and the interfaces for access to genome information. In addition, strategies for continued maintenance and updating need to be developed at the start of the post-genomic era to increase the value of genome sequences into the future.

Aspergillus↗

Dynamics of the IncW genetic backbone imply general trends in conjugative plasmid evolution.

Plasmids cannot be understood as mere tools for genetic exchange: they are themselves subject to the forces of evolution. Their genomic and phylogenetic features have been less studied in this respect. Focusing on the IncW incompatibility group, which includes the smallest known conjugative plasmids, we attempt to unveil some common trends in plasmid evolution. The functional modules of IncW genetic backbone are described, with emphasis on their architecture and relationships to other plasmid groups. Some plasmid regions exhibit strong phylogenetic mosaicism, in striking contrast to others of unusual synteny conservation. The presence of genes of unknown function that are widely distributed in plasmid genomes is also emphasized, exposing the existence of ill-defined yet conserved plasmid functions. Conjugation is an essential hallmark of IncW plasmid biology and special attention is given to the organization and evolution of its transfer modules. Genetic exchange between plasmids and their hosts is analysed by following the evolution of the type IV secretion system. Adaptation of the trw conjugative machinery to pathogenicity functions in Bartonella is discussed as an example of how plasmids can change their host modus vivendi. Starting from the phage paradigm, our analysis articulates novel concepts that apply to plasmid evolution.

Animals↗

Genes lost and genes found: evolution of bacterial pathogenesis and symbiosis.

Traditionally, evolutionary biologists have viewed mutations within individual genes as the major source of phenotypic variation leading to adaptation through natural selection, and ultimately generating diversity among species. Although such processes must contribute to the initial development of gene functions and their subsequent fine-tuning, changes in genome repertoire, occurring through gene acquisition and deletion, are the major events underlying the emergence and evolution of bacterial pathogens and symbionts. Furthermore, pathogens and symbionts depend on similar mechanisms for interacting with hosts and show parallel trends in genome evolution.

Animals↗

The co-evolved Helicobacter pylori and gastric cancer: trinity of bacterial virulence, host susceptibility and lifestyle.

Helicobacter pylori is an important yet unproven etiological agent of gastric cancer. H. pylori infection is more prevalent in developing Asian countries like India and it is usually acquired at an early age. It has been two decades since Marshall and Warren (1984) first described curved bacilli in the stomach of ulcer and gastritis patients. This discovery has won them the Nobel Prize recently, but the debate whether H. pylori is a pathogen or a commensal organism is still hot. Associations with disease-specific factors remain elusive years after the genome sequences were made available. Cytotoxin-associated antigen A (CagA) and the so-called plasticity region cluster genes are implicated in pathogenesis of the carcinoma of stomach. Another virulence factor VacA whose role is still debatable, has recently been projected in pathology of gastric cancer. Studies of the evolution through genetic variation in H. pylori populations have provided a window into the history of human population migrations and a possible co-evolution of this pathogen with its human host. Possible symbiotic relationships were seriously debated since the discovery of this pathogen. The debate has been further intensified as some studies proposed H. pylori infection to be beneficial in some humans. In this commentary, we attempt to briefly discuss about H. pylori as a human pathogen, and some of the important issues linked to its pathophysiology in different hosts. 'We dance around in a ring and suppose, the secret sits in the middle and knows'--Robert Frost.

Journal Article↗

Is pertussis actually reemerging? Insights from an individual-based model.

In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc.), human population structure (individual risk, age structure, interaction matrices, immune response, etc.), as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

Adolescent↗

[Leprosy. Developmental modalities].

The very broad clinical spectrum of the Mycobacterium leprae infection is due to the diversity of the underlying immunological and genetic factors. The evolutive modalities of leprosy are mainly determined by a dual pathogenesis: An infectious disease due to a bacillus of low virulence which, even when dead, persists in the body for several years, independently of the antibiotic therapy prescribed. A dysimmune disease maintained by a chronic discharge of antigens. Neuropathies and leprous reactions are still the most troublesome episodes in the course of the disease. They constitute the principal prognostic factor in both pauci- and multibacillary forms of leprosy.

Humans↗

The genetic basis of thermal reaction norm evolution in lab and natural phage populations.

Two major goals of laboratory evolution experiments are to integrate from genotype to phenotype to fitness, and to understand the genetic basis of adaptation in natural populations. Here we demonstrate that both goals are possible by re-examining the outcome of a previous laboratory evolution experiment in which the bacteriophage G4 was adapted to high temperatures. We quantified the evolutionary changes in the thermal reaction norms--the curves that describe the effect of temperature on the growth rate of the phages--and decomposed the changes into modes of biological interest. Our analysis indicated that changes in optimal temperature accounted for almost half of the evolutionary changes in thermal reaction norm shape, and made the largest contribution toward adaptation at high temperatures. Genome sequencing allowed us to associate reaction norm shape changes with particular nucleotide mutations, and several of the identified mutations were found to be polymorphic in natural populations. Growth rate measures of natural phage that differed at a site that contributed substantially to adaptation in the lab indicated that this mutation also underlies thermal reaction norm shape variation in nature. In combination, our results suggest that laboratory evolution experiments may successfully predict the genetic bases of evolutionary responses to temperature in nature. The implications of this work for viral evolution arise from the fact that shifts in the thermal optimum are characterized by tradeoffs in performance between high and low temperatures. Optimum shifts, if characteristic of viral adaptation to novel temperatures, would ensure the success of vaccine development strategies that adapt viruses to low temperatures in an attempt to reduce virulence at higher (body) temperatures.

Base Sequence↗