Host as the variable: model hosts approach the immunological asymptote.
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Lyssaviruses are unsegmented RNA viruses causing rabies. Their vectors belong to the Carnivora and Chiroptera orders. We studied 36 carnivoran and 17 chiropteran lyssaviruses representing the main genotypes and variants. We compared their genes encoding the surface glycoprotein, which is responsible for receptor recognition and membrane fusion. The glycoprotein is the main protecting antigen and bears virulence determinants. Point mutation is the main force in lyssavirus evolution, as Sawyer's test and phylogenetic analysis showed no evidence of recombination. Tests of neutrality indicated a neutral model of evolution, also supported by globally high ratios of synonymous substitutions (d(S)) to nonsynonymous substitutions (d(N)) (>7). Relative-rate tests suggested similar rates of evolution for all lyssavirus lineages. Therefore, the absence of recombination and similar evolutionary rates make phylogeny-based conclusions reliable. Phylogenetic reconstruction strongly supported the hypothesis that host switching occurred in the history of lyssaviruses. Indeed, lyssaviruses evolved in chiropters long before the emergence of carnivoran rabies, very likely following spillovers from bats. Using dated isolates, the average rate of evolution was estimated to be roughly 4.3 x 10(-4) d(S)/site/year. Consequently, the emergence of carnivoran rabies from chiropteran lyssaviruses was determined to have occurred 888 to 1,459 years ago. Glycoprotein segments accumulating more d(N) than d(S) were distinctly detected in carnivoran and chiropteran lyssaviruses. They may have contributed to the adaptation of the virus to the two distinct mammal orders. In carnivoran lyssaviruses they overlapped the main antigenic sites, II and III, whereas in chiropteran lyssaviruses they were located in regions of unknown functions.
BACKGROUND: Mobile elements are involved in genomic rearrangements and virulence acquisition, and hence, are important elements in bacterial genome evolution. The insertion of some specific Insertion Sequences had been associated with repetitive extragenic palindromic (REP) elements. Considering that there are a sufficient number of available genomes with described REPs, and exploiting the advantage of the traceability of transposition events in genomes, we decided to exhaustively analyze the relationship between REP sequences and mobile elements. RESULTS: This global multigenome study highlights the importance of repetitive extragenic palindromic elements as target sequences for transposases. The study is based on the analysis of the DNA regions surrounding the 981 instances of Insertion Sequence elements with respect to the positioning of REP sequences in the 19 available annotated microbial genomes corresponding to species of bacteria with reported REP sequences. This analysis has allowed the detection of the specific insertion into REP sequences for ISPsy8 in Pseudomonas syringae DC3000, ISPa11 in P. aeruginosa PA01, ISPpu9 and ISPpu10 in P. putida KT2440, and ISRm22 and ISRm19 in Sinorhizobium meliloti 1021 genome. Preference for insertion in extragenic spaces with REP sequences has also been detected for ISPsy7 in P. syringae DC3000, ISRm5 in S. meliloti and ISNm1106 in Neisseria meningitidis MC58 and Z2491 genomes. Probably, the association with REP elements that we have detected analyzing genomes is only the tip of the iceberg, and this association could be even more frequent in natural isolates. CONCLUSION: Our findings characterize REP elements as hot spots for transposition and reinforce the relationship between REP sequences and genomic plasticity mediated by mobile elements. In addition, this study defines a subset of REP-recognizer transposases with high target selectivity that can be useful in the development of new tools for genome manipulation.
This study reports the effects of Trypanosoma cruzi infection induced in C3H/He male and female mice born to chagasic mice. An experimental model was established infecting female C3H/He mice with a low virulent T. cruzi clone. In this model, mating, fertilization, pregnancy evolution and delivery was carried out successfully. The offspring was infected at four, six and eighth weeks of age. The results showed that the offspring born to chagasic mothers present decreased resistance to acquired T. cruzi infection. This decreased resistance was expressed by higher levels of parasitaemia and higher mortality rates in offspring born to chagasic mothers than in controls. Age and sex were shown to be important factors of this phenomenon. The results suggest that maternal immune system products can modulate the immune response of the offspring.
A physical doctor with a PhD in Pathology, Euzenir Nunes Sarno studies the immunology factors of Hansen's disease, one of the oldest chronic infections and that is an exclusively human disease. Staff member of an ambulatory that has become a reference on the disease in Brazil with 220 to 250 new patients per year, Euzenir emphasizes that the fact one cannot cultivate Mycobacterium leprae brings about some everlasting questions in relation to the transmission of and the sensitivity to the disease. There are also many epidemiology questions that remain unanswered. Estimates show that, among those who have contact with multi-bacilli patients, 90% are infected but only about 8% get sick. The high infection rate of those who live with multi-bacilli patients but never fall sick shows that just a small number of individuals are sensitive to Mycobacterium leprae. This is one of the questions immunology has not been able to answer. Why do some people resist to it and some don't? The figures are even lower when compared to those who are in contact with patients that are paucibacillus-infected, i.e. a manifestation of the disease with few bacilli. Hansen's disease is known as a skin malady. But, according to the specialist, its first damage is to the nerve, when the area becomes insensitive. Besides damaging the sensitive skin nerves, the disease can lead to motor disability and irreversible deformities, which sometimes lead to the amputation of limbs and protruded parts of the body. Mycobacterium leprae was one of the first pathogenic bacteria whose genome sequence has been entirely mapped. Only now we have the capacity to have more precise assessments. The disease is not inherited, and only in 1986 health services in Brazil began to take the responsibility for both the disease and its patients. During the twenty-year military dictatorship the country underwent, the health system was dismantled. In 1991, the one-year treatment with three drugs - Dapsone, Rifanpicine and Clofazimine- was introduced in our country. Just 30% of the cases get to negative results after the treatment. according to the interviewee, whereas tuberculosis is a highly virulent multi-bacilli disease, leprosy bacillus is not virulent, is a 'lazy' germ at the end of its evolutional process. One third of its genome does not work.
Problems of microorganism's persistence in infectious pathology are discussed in this work. Persistence of bacteria as the form of procaryotic and eucaryotic cells symbiosis unlimitedly long coexistence is considered. Questions of the microbial evolution formed in constant collision of the infective agent with macroorganism defense mechanisms are discussed. The spectrum of known mechanisms bacterial survival in conditions of an infected organism is considered. For discussion the problem of microbial persistence it is offered to include as model alongside with an independent cell, a microbial population as complex self-organizing system--the original "superorganism" having universal chemical regulation, the determining density of a population and equation of some physiological functions. It is offered to consider the host colonization resistance as a phenomenon of general biology directed on maintenance of a microecological homeostasis as a result of symbiotic interactions of an organism and it autochthonous microflora with the "key" kinds of biotope protection. The use of persistence characteristics of microorganisms is proved as a target in conditions of intermicrobial interaction of its allochthonous and autochthonous microflorae. Practical value of such approach in infectious pathology is shown.
Cellular microbiology is a newly developing science born from the realization that many different aspects of eukaryotic cell biology are targeted by microbial virulence mechanisms. One example of this is the emerging evidence that several bacteria can interfere, directly or indirectly, with the eukaryotic cell cycle. This article discusses the cell-cycle effects of bacterially generated molecules, their role in virulence and their possible therapeutic potential.
The origin of virulence in environmental fungi that have no requirement for animal hosts in their life cycle is enigmatic. Cryptococcus neoformans is a human pathogenic fungus with virulence factors for mammalian pathogenesis that also contribute to environmental survival. C. neoformans virulence may originate from selection pressures imposed by environmental predators.
A group of avian reoviruses comprising serially passaged S1133 strains and their vaccine derivatives was examined biochemically to study the temporal evolution of the viruses and biologically to assess their relative pathogenicities. The strains fell into three groups of differing virulence, the viruses becoming less pathogenic the longer they were passaged. Protein and RNA profiles of the strains showed no distinct patterns of evolution nor any trend that could be correlated with pathogenicity. Nucleic acid hybridization studies of the strains indicated that all the genes were altered to some extent during passage. The S1 and M3 genes appeared to change the most during the first half of passage history, but later, as the virus was cold-adapted or passaged extensively, the M2, S2, and S3 genes also appeared to vary. When viruses were grouped according to virulence, the greatest changes were seen in the S1, M2, and M3 genes, suggesting that these may be associated with the virulence of a given avian reovirus strain.
Yersinia pestis, the causative agent of plague, seems to have evolved from a gastrointestinal pathogen, Yersinia pseudotuberculosis, in just 1,500-20,000 years--an 'eye blink' in evolutionary time. The third pathogenic Yersinia, Yersinia enterocolitica, also causes gastroenteritis but is distantly related to Y. pestis and Y. pseudotuberculosis. Why do the two closely related species cause remarkably different diseases, whereas the distantly related enteropathogens cause similar symptoms? The recent availability of whole-genome sequences and information on the biology of the pathogenic yersiniae have shed light on this paradox, and revealed ways in which new, highly virulent pathogens can evolve.
Two highly infectious bordetellae, Bordetella pertussis and B. parapertussis, have emerged in historical times as co-dominant in human populations. Both of these cause acute disease (whooping cough), whereas their progenitor, B. bronchiseptica, is of variable virulence in a wide variety of animals. The remarkably close phylogenetic relatedness of these three bordetellae and the two independent jumps to humans provide a unique opportunity to examine the evolution and genetics involved in the emergence of acute human pathogens. We hypothesize that the more virulent strains in humans reflects how acutely infectious pathogens might be favored in communities with large contact networks. Furthermore, we suggest that the differential expression of the various virulence factors by the two human pathogens can be explained by immune-mediated competition between the strains. The evolutionarily favored strategies of both of the human bordetellae result in immunizing infections and acute epidemics.
Streptococcal fibronectin-binding protein is an important virulence factor involved in colonization and invasion of epithelial cells and tissues by Streptococcus pyogenes. In order to investigate the mechanisms involved in the evolution of sfbI, the sfbI genes from 54 strains were sequenced. Thirty-four distinct alleles were identified. Three principal mechanisms appear to have been involved in the evolution of sfbI. The amino-terminal aromatic amino acid-rich domain is the most variable region and is apparently generated by intergenic recombination of horizontally acquired DNA cassettes, resulting in a genetic mosaic in this region. Two distinct and divergent sequence types that shared only 61 to 70% identity were identified in the central proline-rich region, while variation at the 3' end of the gene is due to deletion or duplication of defined repeat units. Potential antigenic and functional variabilities in SfbI imply significant selective pressure in vivo with direct implications for the microbial pathogenesis of S. pyogenes.
Streptococcus thermophilus is a major dairy starter used for the manufacture of yoghurt and cheese. The access to three genome sequences, comparative genomics and multilocus sequencing analyses suggests that this species recently emerged and is still undergoing a process of regressive evolution towards a specialised bacterium for growth in milk. Notably, S. thermophilus has maintained a well-developed nitrogen metabolism whereas its sugar catabolism has been subjected to a high level of degeneracy due to a paucity of carbon sources in milk. Furthermore, while pathogenic streptococci are recognised for a high capacity to expose proteins at their cell surface in order to achieve cell adhesion or to escape the host immune system, S. thermophilus has nearly lost this unique feature as well as many virulence-related functions. Although gene decay is obvious in S. thermophilus genome evolution, numerous small genomic islands, which were probably acquired by horizontal gene transfer, comprise important industrial phenotypic traits such as polysaccharide biosynthesis, bacteriocin production, restriction-modification systems or oxygen tolerance.
By exploiting the ability of Pseudomonas aeruginosa to infect a variety of vertebrate and nonvertebrate hosts, we have developed model systems that use plants and nematodes as adjuncts to mammalian models to help elucidate the molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable degree of conservation in the virulence mechanisms used by P. aeruginosa to infect hosts of divergent evolutionary origins.
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Although the causative agent has long been identified and a safe, effective vaccine is available, yellow fever still poses a threat in South America and tropical areas of Africa where it mainly affects young people. The presentation of yellow fever has changed relatively little since description of the first outbreaks, but study has entered a new age thanks to development of more accurate techniques for characterization of viral strains. Comparison of the RNA sequences of virus from different geographical regions has demonstrated the existence of several stable genotypes which have been designated as topotypes. These topotypes have yet to be correlated with different viral activity but their recognition has allowed better epidemiologic surveillance of the disease. Study of the viral genome has also allowed improvement of diagnostic techniques, identification of factors influencing virulence, and enhancement of understanding of viral mutations. Ultimately knowledge of the processes underlying viral evolution could assist development of effective preventive strategies.
Human skeletal evidence for the emergence of chronic infectious disease in northern Vietnam is examined. The sample includes the remains of 192 individuals representing the Mid-Holocene and Bronze to Iron Ages. The objective is to see if the transition from sedentary, foraging, coastally oriented economies to centralized chiefdoms with attendant development and intensification of agriculture, trade, metal technologies, warfare, and population increase was accompanied by an emergence of and/or increase in infectious disease. It was found that skeletal evidence for infectious disease was absent in the Mid-Holocene, while over 10% of the Metal period sample exhibited lesions consistent with either infectious disease or immune system disorders. Factors potentially contributing to the emergence of infectious disease in northern Vietnam in the Metal period include: increased contact with bacterial or fungal pathogens either directly or by way of vertebrate and/or arthropod vectors; higher levels of debilitation and/or decreased levels of immunocompetence in the Metal period; and evolution of pathogens present in Mid-Holocene human hosts into more virulent forms in the Metal period. The first two factors may be related to historically and archaeologically documented major demographic (Han colonizing efforts) and economic (agricultural intensification) changes in the region during the Metal period.
To probe the evolution of internalins with confirmed or suspected roles in Listeria monocytogenes virulence we sequenced the full inlB, inlC2, inlC, inlD, inlE, inlF, inlG, and inlH ORFs from 40 L. monocytogenes isolated from human (n=10) and animal (n=10) clinical cases, foods (n=10), and the natural environment (n=10). inlB and inlE were present in all isolates, representing 26 and 20 alleles, respectively. inlC was found in all lineage I and II isolates and represented 21 alleles. inlC2 and inlD represented 22 and 24 alleles, respectively, and were found in all L. monocytogenes isolates, with the exception of three lineage II isolates, which carried inlH, an apparent fusion of the 5' end of inlC2 with the 3' end of inlD. inlF and inlG were absent from lineage I isolates and represented 16 and 11 alleles, respectively. Average pairwise nucleotide differences per site (pi) ranged from 0.00849 (inlF) to 0.07020 (inlE). Phylogenetic trees generally showed clustering of internalin genes into two major evolutionary lineages consistent with lineages I and II previously assigned by ribotyping. In addition to detection of recombination events within each internalin gene, inlB, inlC, inlC2, and inlF showed significant evidence for positive selection (i.e., selection for an advantageous mutant allele). Overall, our data indicated that (i) internalin genes are highly diverse, (ii) internalin gene sequences cluster consistent with the phylogenetic lineages of L. monocytogenes, (iii) both intragenic recombination and positive selection have contributed to the evolution of L. monocytogenes internalins, and (iv) L. monocytogenes internalins show distinct evolutionary histories.