Bacterial pathogenicity islands

The information on the key pathogenicity factors of uropathogenic and enteropathogenic Escherichia coli, Shigella, Salmonella, Vibrio cholerae, Yersinia, Listeria and Helicobacter pylori is reviewed. The analysis of data on pathogenicity "islands" and "islets" of infective agents is given. The problems of the genetic control of pathogenicity factors and the functions of pathogenicity "islands", found in infective agents, are discussed.     

The factors of bacterial pathogenicity and their role in the development of the infectious process

The latest data concerning the characterization of the pathogenicity factors of bacteria and the evaluation of their role in the realization of definite phases of the development of the infectious process are presented. The infectious process is regarded as the result of the complicated simultaneous interaction of microorganisms and different cells and tissues of the host body. The problems of the polydeterminant character of pathogenicity factors, tho possibility of the joint action of different factors at one and the same stage of the development of the infectious process and, vice versa, the action of the same factors at different stages of the interaction of the infective agent and the susceptible host are discussed. Modern data on the genetic control of pathogenicity factors, on the localization of their genetic determinants on the chromosome and the virulence plasmids, information of pathogenicity "islets" which jointly determine the pathogenic potential of the infective agent are given. The emphasis is made on fact that the general principle of the genetic control of bacterial pathogenicity is complicated relationship between chromosomal and nonchromosomal determinants; some of them form a part of genetic pathogenicity "islets", simultaneously regulating and expressing the pathogenicity factors of the infective agent.     

Clinical strains of <Emphasis Type="Italic">Streptococcus agalactiae</Emphasis> carry two different variants of pathogenicity island XII

Streptococcus agalactiae or Group B streptococci (GBS) are a common cause of serious diseases of newborns and adults. GBS pathogenicity largely depends on genes located on the accessory genome including several pathogenicity islands (PAI). The present paper is focused on the structure and molecular epidemiological analysis of one of the GBS pathogenicity islands—the pathogenicity island PAI XII (Glaser et al. Mol Microbiol 45(6):1499–1513, 2002). This PAI was found to be composed of three different mobile genetic elements: a composite transposon (PAI-C), a genomic islet (PAI-B), and a pathogenicity island associated with gene sspB1 (PAI-A). PAI-A in GBS has a homolog——PAI-A1 with similar, but a different genetic constellation. PCR-based analysis of GBS collections from different countries revealed that a strains lineage with PAI-A is less common than PAI-A1 and was determined to be present only among the strains obtained from Russia. Our results suggest that PAI-A and PAI-A1 have the same progenitor, which evolved independently and appeared in the GBS genome as separate genetic events. Results of this study reflect specific geographical distribution of the GBS strains with the mobile genetic element under study.     

Participation of mobile elements in formation of properties of pathogenic bacteria]

Published reports about structural organization of genes coding for pathogenicity factors are reviewed. Many of such genes are often united into "virulence blocks" or "pathogenicity islands" and are surrounded by mobile genetic elements, promoting their transposition between related bacteria genomes and leading to changes in virulence in the course of evolution. Data on the similarity of nucleotide sequences of virulence genes in different bacteria are presented, despite differences in their localization in the relevant genomes. The role of rRNA genes in dissemination of virulence genes among different bacteria during transduction or conjugation is shown.     

Excision of an unstable pathogenicity island in Salmonella enterica serovar Enteritidis is induced during infection of phagocytic cells

The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis), a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated "regions of difference" (ROD). In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells.     

The molecular basis of infectious diseases: pathogenicity islands and other mobile genetic elements. A review

Bacterial genomes generally consist of stable regions termed core genome, and variable regions that form the so-called flexible gene pool. The flexible part is composed of bacteriophages, plasmids, transposons as well as unstable large regions that have been termed genomic islands. Genomic islands encoding virulence factors of pathogenic bacteria have been designated "pathogenicity islands". Pathogenicity islands were first discovered in uropathogenic Escherichia coli and presently more than 30 bacterial species carrying pathogenicity islands have been described. This review summarises the current knowledge on bacterial genomic islands and their general features, and discusses their putative role in the evolution of microbes in the light of genomics of pathogenic bacteria.     

致病岛及其分泌系统

致病岛是指细菌染色体上一段具有典型结构特征的基因簇,主要编码与细菌的毒力及代谢等功能相关的产物。病原菌必须要有一套高效的分泌系统才能将致病因子分泌到细菌表面或转运出细胞,并尽可能进入宿主细胞。现在已经发现了至少5套不同的蛋白分泌系统。本文就致病岛及其分泌系统的相关研究进展作一综述。     

PIPS: pathogenicity island prediction software

The adaptability of pathogenic bacteria to hosts is influenced by the genomic plasticity of the bacteria, which can be increased by such mechanisms as horizontal gene transfer. Pathogenicity islands play a major role in this type of gene transfer because they are large, horizontally acquired regions that harbor clusters of virulence genes that mediate the adhesion, colonization, invasion, immune system evasion, and toxigenic properties of the acceptor organism. Currently, pathogenicity islands are mainly identified in silico based on various characteristic features: (1) deviations in codon usage, G+C content or dinucleotide frequency and (2) insertion sequences and/or tRNA genetic flanking regions together with transposase coding genes. Several computational techniques for identifying pathogenicity islands exist. However, most of these techniques are only directed at the detection of horizontally transferred genes and/or the absence of certain genomic regions of the pathogenic bacterium in closely related non-pathogenic species. Here, we present a novel software suite designed for the prediction of pathogenicity islands (pathogenicity island prediction software, or PIPS). In contrast to other existing tools, our approach is capable of utilizing multiple features for pathogenicity island detection in an integrative manner. We show that PIPS provides better accuracy than other available software packages. As an example, we used PIPS to study the veterinary pathogen Corynebacterium pseudotuberculosis, in which we identified seven putative pathogenicity islands.     

Host specificity determinants as a genetic continuum

Host specificity is an important concept that underlies the interaction of all clinically and agriculturally relevant microbes with their hosts. Changes in the host specificity of animal pathogens, in particular, are often of greatest concern due to their immediate and unexpected impact on human health. Host switching or host jumps can often be traced to modification of key microbial pathogenicity factors that facilitate the formation of particular host associations. An increase in the number of genome-level studies has begun revealing that almost any type of change, from the simplest to the most complex, can potentially impact host specificity. This review highlights examples of host specificity determinants of viruses, bacteria and fungi, and presents them from within a genetic continuum that spans from the single residue through to entire genomic islands.     

Characterization and expression analysis of Staphylococcus aureus pathogenicity island 3. Implications for the evolution of staphylococcal pathogenicity islands

We describe the complete sequence of the 15.9-kb staphylococcal pathogenicity island 3 encoding staphylococcal enterotoxin serotypes B, K, and Q. The island, which meets the generally accepted definition of pathogenicity islands, contains 24 open reading frames potentially encoding proteins of more than 50 amino acids, including an apparently functional integrase. The element is bordered by two 17-bp direct repeats identical to those found flanking staphylococcal pathogenicity island 1. The island has extensive regions of homology to previously described pathogenicity islands, particularly staphylococcal pathogenicity islands 1 and bov. The expression of 22 of the 24 open reading frames contained on staphylococcal pathogenicity island 3 was detected either in vitro during growth in a laboratory medium or serum or in vivo in a rabbit model of toxic shock syndrome using DNA microarrays. The effect of oxygen tension on staphylococcal pathogenicity island 3 gene expression was also examined. By comparison with the known staphylococcal pathogenicity islands in the context of gene expression described here, we propose a model of pathogenicity island origin and evolution involving specialized transduction events and addition, deletion, or recombination of pathogenicity island "modules."     

李斯特菌毒力因子及其进化

李斯特菌属包含6个种,毒力各有差异。在细菌耐受外界环境、黏附侵袭及细胞内感染过程中,毒力因子各司其职又相互协作。毒力基因常聚集为毒力岛,其中PrfA依赖型毒力基因簇(LIPI-1)与内化素岛(LIPI-2)是致病种最重要的两个毒力岛。李斯特菌各个种可能来源于同一个携带有完整毒力岛的祖先,在长期进化过程中,通过基因水平转移或重组、整合等事件,演化为目前流行的6个种。噬菌体、转座子、质粒等可能扮演着毒力进化执行者的角色。一些天然非典型菌株是目前研究的热点,如含有LIPI-1的无害李斯特菌和缺失LIPI-1的塞氏李斯特菌,其演化进程可能尚未达到或已超越目前流行的状态,为李斯特菌毒力进化的研究提供了重要线索。     

Genome sequence of Streptococcus agalactiae,a pathogen causing invasive neonatal disease

Streptococcus agalactiae is a commensal bacterium colonizing the intestinal tract of a significant proportion of the human population. However, it is also a pathogen which is the leading cause of invasive infections in neonates and causes septicaemia, meningitis and pneumonia. We sequenced the genome of the serogroup III strain NEM316, responsible for a fatal case of septicaemia. The genome is 2 211 485 base pairs long and contains 2118 protein coding genes. Fifty-five per cent of the predicted genes have an ortholog in the Streptococcus pyogenes genome, representing a conserved backbone between these two streptococci. Among the genes in S. agalactiae that lack an ortholog in S. pyogenes, 50% are clustered within 14 islands. These islands contain known and putative virulence genes, mostly encoding surface proteins as well as a number of genes related to mobile elements. Some of these islands could therefore be considered as pathogenicity islands. Compared with other pathogenic streptococci, S. agalactiae shows the unique feature that pathogenicity islands may have an important role in virulence acquisition and in genetic diversity.     

The Pseudomonas aeruginosa Pathogenicity Island PAPI-1 Is Transferred via a Novel Type IV Pilus

Pseudomonas aeruginosa is a major cause of nosocomial infections, particularly in immunocompromised patients or in individuals with cystic fibrosis. The notable ability of P. aeruginosa to inhabit a broad range of environments, including humans, is in part due to its large and diverse genomic repertoire. The genomes of most strains contain a significant number of large and small genomic islands, including those carrying virulence determinants (pathogenicity islands). The pathogenicity island PAPI-1 of strain PA14 is a cluster of 115 genes, and some have been shown to be responsible for virulence phenotypes in a number of infection models. We have previously demonstrated that PAPI-1 can be transferred to other P. aeruginosa strains following excision from the chromosome of the donor. Here we show that PAPI-1 is transferred into recipient P. aeruginosa by a conjugative mechanism, via a type IV pilus, encoded in PAPI-1 by a 10-gene cluster which is closely related to the genes in the enterobacterial plasmid R64. We also demonstrate that the precursor of the major pilus subunit, PilS2, is processed by the chromosomally encoded prepillin peptidase PilD but not its paralog FppA. Our results suggest that the pathogenicity island PAPI-1 may have evolved by acquisition of a conjugation system but that because of its dependence on an essential chromosomal determinant, its transfer is restricted to P. aeruginosa or other species capable of providing a functional prepilin peptidase.The genomes of a number of microorganisms, primarily those that have a capability of changing and adapting to a wide range of environments, evolve by acquisition of novel genetic information in blocks of genes via a process referred to as horizontal gene transfer (HGT). Other bacterial species change their genetic repertoire minimally, principally those that have adapted to a particular environment and, in the case of pathogenic bacteria, to a specific host. For HGT-mediated acquisition of genes to occur, a recipient has to be in an environment where donor genetic material is available, such as different strains of the same species cohabitating a shared niche or growing in a large and diverse community of several hundred different microorganisms. Moreover, for bacteria to become successful recipients of foreign genetic material, they have to posses one of three mechanisms of HGT: natural competence for uptake of foreign DNA (transformation), the ability to be infected by transducing bacteriophages (transduction), or serving as recipients during conjugation of plasmids or mobilized chromosomal DNA (conjugation). Acquired genetic material can consist of individual genes, where they recombine into homologous sequences in the recipient genome and thus increase the genetic diversity. However, large blocks of hundreds of contiguous genes in elements called genomic islands can be also transferred between bacteria, allowing the recipient microorganisms to acquire a number of new traits by a single HGT event.Previous studies comparing genomes of the opportunistic pathogen Pseudomonas aeruginosa pointed toward HGT as an important factor in its evolution (23). The genomes of all strains sequenced to date contain a significant fraction of horizontally acquired genes, in genomic islands and prophages, consisting of a few to several hundred. These islands can be recognized by the presence of certain signature features, such as an atypical nucleotide composition relative to the rest of the genome, location within predicted sites of chromosomal integration (att sites), and the presence of genes encoding bacteriophages and conjugation machineries. We have recently demonstrated that PAPI-1, a large P. aeruginosa genomic (pathogenicity) island, can be excised from its tRNA att site and that a copy can be transferred into a recipient, where it integrates into the same tRNA gene (27). Inspection of the genes in PAPI-1 and features of the transfer process, namely, an integrase-dependent excision and formation of a circular intermediate, suggested that PAPI-1 is an integrative and conjugative element and that it is likely transferred by a conjugative mechanism.Here we extended our analysis of PAPI-1 by testing its transfer from a preselected group of P. aeruginosa PA14 mutants with insertions in each of the genes on the island. Among those mutants that were defective in PAPI-1 transfer, one group of genes encode homologs of type IV pilus proteins. While type IV pili have been found to be involved primarily in bacterial adhesion and twitching motility (24), the PAPI-1-encoded pilus is closely related to the conjugative apparatus of plasmid R64 (14). Moreover, we show that an essential posttranslational modification reaction, converting the precursor of the major pilin subunit encoded in PAPI-1 into a mature protein, is carried out by an enzyme encoded in the chromosome of the donor cells. The acquisition and adaptation of groups of genes and subsequent loss of an essential function may represent a novel evolutionary strategy, limiting horizontal transfer to a specific bacterial species.     

Hybrid pathogenicity island PAGI-5 contributes to the highly virulent phenotype of a Pseudomonas aeruginosa isolate in mammals

Most known virulence determinants of Pseudomonas aeruginosa are remarkably conserved in this bacterium's core genome, yet individual strains differ significantly in virulence. One explanation for this discrepancy is that pathogenicity islands, regions of DNA found in some strains but not in others, contribute to the overall virulence of P. aeruginosa. Here we employed a strategy in which the virulence of a panel of P. aeruginosa isolates was tested in mouse and plant models of disease, and a highly virulent isolate, PSE9, was chosen for comparison by subtractive hybridization to a less virulent strain, PAO1. The resulting subtractive hybridization sequences were used as tags to identify genomic islands found in PSE9 but absent in PAO1. One 99-kb island, designated P. aeruginosa genomic island 5 (PAGI-5), was a hybrid of the known P. aeruginosa island PAPI-1 and novel sequences. Whereas the PAPI-1-like sequences were found in most tested isolates, the novel sequences were found only in the most virulent isolates. Deletional analysis confirmed that some of these novel sequences contributed to the highly virulent phenotype of PSE9. These results indicate that targeting highly virulent strains of P. aeruginosa may be a useful strategy for identifying pathogenicity islands and novel virulence determinants.     

细菌中基因组岛的转移与调控机制研究进展

基因水平转移可导致细菌不同种属间个体DNA的交换,从而使细菌对环境的适应性增强,是细菌进化的重要途径之一。基因组岛是基因水平转移的重要载体,可移动的基因组岛能够整合到宿主的染色体上,并在特定的条件下切除,进而通过转化、接合或转导等方式转移到新的宿主中。基因组岛具有多种生物学功能,如抗生素抗性、致病性、异源物质降解、重金属抗性等。基因组岛的转移造成可变基因在不同种属细菌间的广泛传播,例如毒力和耐药基因的传播导致了多重耐药细菌的产生,威胁人类健康。基因组岛由整合酶介导转移,同时在转移的过程受到多种不同转录因子的调控。本文对细菌中基因组岛的结构特点、转移和调控机制以及预测等方面进行了综述,并最终阐明基因组岛的转移及其调控机制是遏制基因组岛传播的重要策略。     

Pathogenicity islands in opportunistic Enterobacteria

The presence of fragments of genomes hlyA, hlyB, papAH, papC, sfaG, sfaA and kps MT, associated with the pathogenicity islands of Escherichia coli, in clinical strains of other genera of the family Enterobacteriaceae, has been experimentally evaluated with the use of PCR. The presence of DNA fragments specific to the known genes of the pathogenicity clusters of E. coli in representatives of the genera Citrobacter, Enterobacter, Hafnia, Klebsiella, Morganella, Proteus, Providencia, Serratia and Yersinia of rarely occurring groups has been established. In Enterobacteriaceae cultures isolated from the intestine amplicons homologous to hlyB were detected significantly less frequently than among strains of nonintestinal origin. In Enterobacteriaceae strains isolated in respiratory pathology amplicons of the pili gene (sfaG) were detected significantly more frequently than in collection cultures. The total evaluation of the detection rate of the genes of pathogenicity islands among Enterobacteriaceae clinical strains under study in comparison with E. coli showed that they occurred significantly less frequently. Klebsiella spp. were found to differ most essentially from E. coli as regards the occurrence of fragments of the genes of pathogenicity islands. The conclusion was made on the high probability of genetic exchange in DNA fragments between different species of bacteria with corresponding changes in their pathogenicity.     

Evolutionary perspective on the origin of Haitian cholera outbreak strain

Cholera epidemic has not been reported in Haiti for at least 100 years, although cholera has been present in Latin America since 1991. Surprisingly, the recent cholera epidemic in Haiti (October 2010) recorded more than 250,000 cases and 4000 deaths in the first 6 months and became one of the most explosive and deadly cholera outbreak in recent history. In the present study, we conducted genomic analyses of pathogenicity islands of three Haitian Vibrio cholerae strains and compared them with nine different V. cholerae O1 El Tor genomes. Although CIRS101 is evolutionarily most similar to the Haitian strains, our study also provides some important differences in the genetic organization of pathogenicity islands of Haitian strains with CIRS101. Evolutionary analysis suggests that unusual functional constraints have been imposed on the Haitian strains and we hypothesize that amino acid substitution is more deleterious in Haitian strains than in nonHaitian strains.     

Adjacent location of thebac gene and two-component regulatory system genes within the putativeStreptococcus agalactiae pathogenicity island

A chromosomal DNA fragment of 8992 bp in size that has not been previously identified in Streptococcus agalactiae, was cloned and sequenced from strain 98-D60C. In particular, this 8992-bp fragment contained genes homologous to the sensor histidine kinase gene and the DNA-binding response-regulator gene of Streptococcus pneumoniae, and S. agalactiae bac gene. Structural and genetic features of the 8992-bp fragment were highly similar to those specific for bacterial pathogenicity islands. Analysis of epidemiologically unrelated S. agalactiae strains revealed that this fragment was present only in bac gene-positive strains. The possible origin of the 8992-bp fragment in S. agalactiae and its significance for molecular mechanisms of "bacteria-host" interactions are discussed.     

Genomic analysis of ICEVchBan8: An atypical genetic element in Vibrio cholerae

Genomic islands (GIs) and integrative conjugative elements (ICEs) are major players in bacterial evolution since they encode genes involved in adaptive functions of medical or environmental importance. Here we performed the genomic analysis of ICEVchBan8, an unusual ICE found in the genome of a clinical non-toxigenic Vibrio cholerae O37 isolate. ICEVchBan8 shares most of its genetic structure with SXT/R391 ICEs. However, this ICE codes for a different integration/excision module is located at a different insertion site, and part of its genetic cargo shows homology to other pathogenicity islands of V. cholerae.     

Evolutionary perspective on the origin of Haitian cholera outbreak strain

Cholera epidemic has not been reported in Haiti for at least 100?years, although cholera has been present in Latin America since 1991. Surprisingly, the recent cholera epidemic in Haiti (October 2010) recorded more than 250,000 cases and 4000 deaths in the first 6?months and became one of the most explosive and deadly cholera outbreak in recent history. In the present study, we conducted genomic analyses of pathogenicity islands of three Haitian Vibrio cholerae strains and compared them with nine different V. cholerae O1 El Tor genomes. Although CIRS101 is evolutionarily most similar to the Haitian strains, our study also provides some important differences in the genetic organization of pathogenicity islands of Haitian strains with CIRS101. Evolutionary analysis suggests that unusual functional constraints have been imposed on the Haitian strains and we hypothesize that amino acid substitution is more deleterious in Haitian strains than in nonHaitian strains.