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Type IV secretion systems (T4SSs) mediate horizontal gene transfer, thus contributing to genome plasticity, evolution of infectious pathogens, and dissemination of antibiotic resistance and other virulence traits. A gene cluster of the Haemophilus influenzae genomic island ICEHin1056 has been identified as a T4SS involved in the propagation of genomic islands. This T4SS is novel and evolutionarily distant from the previously described systems. Mutation analysis showed that inactivation of key genes of this system resulted in a loss of phenotypic traits provided by a T4SS. Seven of 10 mutants with a mutation in this T4SS did not express the type IV secretion pilus. Correspondingly, disruption of the genes resulted in up to 100,000-fold reductions in conjugation frequencies compared to those of the parent strain. Moreover, the expression of this T4SS was found to be positively regulated by one of its components, the tfc24 gene. We concluded that this gene cluster represents a novel family of T4SSs involved in propagation of genomic islands.

We classified diversity in eight new complete mitochondrial genome sequences and 41 partial sequences from living Aboriginal Australians into five haplogroups. Haplogroup AuB belongs to global lineage M, and AuA, AuC, AuD, and AuE to N. Within N, we recognize subdivisions, assigning AuA to haplogroup S, AuD to haplogroup O, AuC to P4, and AuE to P8. On available evidence, [sup.S]AuA and [sup.M]AuB are widespread in Australia. [.sup.P4]AuC is found in the Riverine region of western New South Wales, and was identified by others in northern Australia. [sup.O]AuD and [sup.P8]AuE were clearly identified only from central Australia. Our eight Australian full mt genome sequences, combined with 20 others (Ingman and Gyllensten [2003] Genome Res. 13:1600-1606) and compared with full mt genome sequences from regions to the north that include Papua New Guinea, Malaya, and Andaman and Nicobar Islands, show that ancestral connections between regions are deep and limited to clustering at the level of the N and M macrohaplogroups. The Australian-specific distribution of the five haplogroups identified indicates genetic isolation over a long period. Ancestral connections within Australia are deeper than those reflected by known linguistic or culturally based affinities. Applying a coalescence analysis to a gene tree for the coding regions of the eight genomic sequences, we made estimates of time depth that support a continuity of presence for the descendants of a founding population already established by 40,000 years ago. KEY WORDS mtDNA; phylogeography; coalescence model; population history

The population structure of group B streptococcus (GBS) from a low-incidence region for invasive neonatal disease (Israel) was investigated using multilocus genotype data. The strain collection consisted of isolates from maternal carriage (n = 104) and invasive neonatal disease (n = 50), resolving into 46 sequence types. The most prevalent sequence types were ST-1 (17-5%), ST-19 (10.4%), ST-17 (9.7%), ST-22 (8.4%) and ST-23 (6.5%). Serotype III was the most common, accounting for 29.2% of the isolates. None of the serotypes was significantly associated with invasive neonatal disease. BURST analysis resolved the 46 sequence types into seven lineages (clonal complexes), from which only lineage ST-17, expressing serotype III only, was significantly associated with invasive neonatal disease. Lineage ST-22 expressed mainly serotype II, and was significantly associated with carriage. The distribution of the various sequence types and lineages, and the association of lineage ST-17 with invasive disease, are consistent with the results of analyses from a global GBS isolate collection. These findings could imply that the global variation in disease incidence is independent of the circulating GBS populations, and may be more affected by other risk factors for invasive GBS disease, or by different prevention strategies.

The recent emergence of the human-pathogenic Vibrio vulnificus in Israel was investigated by using multilocus genotype data and modern molecular evolutionary analysis tools. We show that this pathogen is a [...]

Transferable antibiotic resistance in Haemophilus influenzae was first detected in the early 1970s. After this, resistance spread rapidly worldwide and was shown to be transferred by a large 40- to 60-kb conjugative element. Bioinformatics analysis of the complete sequence of a typical H. influenzae conjugative resistance element, ICEHin1056, revealed the shared evolutionary origin of this element. ICEHin1056 has homology to 20 contiguous sequences in the National Center for Biotechnology Information database. Systematic comparison of these homologous sequences resulted in identification of a conserved syntenic genomic island consisting of up to 33 core genes in 16 [beta]- and [gamma]-Proteobacteria. These diverse genomic islands shared a common evolutionary origin, insert into tRNA genes, and have diverged widely, with G+C contents ranging from 40 to 70% and amino acid homologies as low as 20 to 25% for shared core genes. These core genes are likely to account for the conjugative transfer of the genomic islands and may even encode autonomous replication. Accessory gene clusters were nestled among the core genes and encode the following diverse major attributes: antibiotic, metal, and antiseptic resistance; degradation of chemicals; type IV secretion systems; two-component signaling systems; Vi antigen capsule synthesis; toxin production; and a wide range of metabolic functions. These related genomic islands include the following well-characterized structures: SPI-7, found in Salmonella enterica serovar Typhi; PAP1 or pKLC102, found in Pseudomonas aeruginosa; and the clc element, found in Pseudomonas sp. strain B13. This is the first report of a diverse family of related syntenic genomic islands with a deep evolutionary origin, and our findings challenge the view that genomic islands consist only of independently evolving modules.

There has been considerable recent interest in understanding the way in which recombination rates vary over small physical distances, and the extent of recombination hotspots, in various genomes. Here we adapt, apply, and assess the power of recently developed coalescent-based approaches to estimating recombination rates from sequence polymorphism data. We apply full-likelihood estimation to study rate variation in and around a well-characterized recombination hotspot in humans, in the [beta]-globin gene cluster, and show that it provides similar estimates, consistent with those from sperm studies, from two populations deliberately chosen to have different demographic and selectional histories. We also demonstrate how approximate-likelihood methods can be used to detect local recombination hotspots from genomic-scale SNP data. In a simulation study based on 80 100-kb regions, these methods detect 43 out of 60 hotspots (ranging from 1 to 2 kb in size), with only two false positives out of 2000 subregions that were tested for the presence of a hotspot. Our study suggests that new computational tools for sophisticated analysis of population diversity data are valuable for hotspot detection and fine-scale mapping of local recombination rates.

A computer simulation model proposed for the genesis of a locus of variable numbers of tandern repeats (VNTRs) facilitated the analyses of additional rates as well as distinct constraints of recombination. The analyses, confined to population genetics of VNTRs, hypothesize the neutrality of VNTRs and the initial evanescence of VNTR polymorphism. The validation of the intrinsically poor fit to the infinite alleles models of simulated VNTR variations and estimated VNTR polymorphism derivatives of two Papua New Guinean populations.

A model describing the evolutionary persistence of single tandemly repetitive DNA (TR-DNA) is analyzed. The study assumes that variable numbers of tandem repeats (VNTRs) can be grouped with satellite DNAs to create a class of TR-DNA. The evolutionary process is likewise assumed to flow from an unbiased recombinational process. Results show that misalignment constraint generates VNTR loci evolution including minisatellites. The results support nonrandom VNTR and other TR-DNA distributions in the human genome.

The pattern of allelic sequence polymorphism in part of the gene for the pyruvate dehydrogenase E1 alpha subunit (PDHA1) exhibits an unusual characteristic. The alleles at the PDHA1 locus completely segregate between samples of 16 Africans and 19 non-Africans. Furthermore, the levels of diversity are entirely discordant between these samples. PDHA1 is on the X chromosome which, previous to this study, had been deemed similar to the polymorphic patterns of the loci from autosomal chromosomes.

Background: Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea and is endemic in hospitals, hindering the identification of sources and routes of transmission based on shared time and space alone. This may compromise rational control despite costly prevention strategies. This study aimed to investigate ward-based transmission of C. difficile, by subdividing outbreaks into distinct lineages defined by multi-locus sequence typing (MLST). Methods and Findings: All C. difficile toxin enzyme-immunoassay-positive and culture-positive samples over 2.5 y from a geographically defined population of ~600,000 persons underwent MLST. Sequence types (STs) were combined with admission and ward movement data from an integrated comprehensive healthcare system incorporating three hospitals (1,700 beds) providing all acute care for the defined geographical population. Networks of cases and potential transmission events were constructed for each ST. Potential infection sources for each case and transmission timescales were defined by prior ward-based contact with other cases sharing the same ST. From 1 September 2007 to 31 March 2010, there were means of 102 tests and 9.4 CDIs per 10,000 overnight stays in inpatients, and 238 tests and 15.7 CDIs per month in outpatients/primary care. In total, 1,276 C. difficile isolates of 69 STs were studied. From MLST, no more than 25% of cases could be linked to a potential ward-based inpatient source, ranging from 37% in renal/transplant, 29% in haematology/oncology, and 28% in acute/elderly medicine to 6% in specialist surgery. Most of the putative transmissions identified occurred shortly (≤ 1 wk) after the onset of symptoms (141/218, 65%), with few >8 wk (21/218, 10%). Most incubation periods were ≤ 4 wk (132/218, 61%), with few >12 wk (28/218, 13%). Allowing for persistent ward contamination following ward discharge of a CDI case did not increase the proportion of linked cases after allowing for random meeting of matched controls. Conclusions: In an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic enzyme-immunoassay-positive patients cannot account for most new CDI cases. Please see later in the article for the Editors' Summary., Introduction Infection with Clostridium difficile is a leading cause of healthcare-associated diarrhoea, which is almost exclusively precipitated by antibiotic exposure that disturbs the normal intestinal flora, allowing C. difficile to [...]

Society's health care puts demands on clinical medicine that motivate basic scientific research. In return, scientific research informs clinical medicine, defining our society's health care options. Unless there is communication, [...]