Biomedical subjects

D Ashley Robinson

Publications and source records attributed to D Ashley Robinson.

13 recordsLinked to original sources

PubMed2006

Evolution and global dissemination of macrolide-resistant group A streptococci.

Macrolide-resistant group A streptococci (MRGAS) have been recovered from many countries worldwide. However, the strain typing information that is available has been insufficient for estimating the total number of macrolide-resistant clones, their geographic distributions, and their evolutionary relationships. In this study, sequence-based strain typing was used to characterize 212 MRGAS isolates from 34 countries. Evaluation of clonal complexes, emm type, and resistance gene content [erm(A), erm(B), mef(A), and undefined] indicate that macrolide resistance was acquired by GAS organisms via > or independent genetic events. In contrast to other collections of mostly susceptible GAS, genetic diversification of MRGAS clones has occurred primarily by mutation rather than by recombination. Twenty-two MRGAS clonal complexes were recovered from more than one continent; intercontinental strains represent nearly 80% of the MRGAS isolates under study. The findings suggest that horizontal transfer of macrolide resistance genes to numerous genetic backgrounds and global dissemination of resistant clones and their descendants are both major components of the present-day macrolide resistance problem found within this species.

Biological Evolution↗

PubMed2006

Multilocus sequence typing scheme for Enterococcus faecalis reveals hospital-adapted genetic complexes in a background of high rates of recombination.

A multilocus sequence typing (MLST) scheme based on seven housekeeping genes was used to investigate the epidemiology and population structure of Enterococcus faecalis. MLST of 110 isolates from different sources and geographic locations revealed 55 different sequence types that grouped into four major clonal complexes (CC2, CC9, CC10, and CC21) by use of eBURST. Two of these clonal complexes, CC2 and CC9, are particularly fit in the hospital environment, as CC2 includes the previously described BVE clonal complex identified by an alternative MLST scheme and CC9 includes exclusively isolates from hospitalized patients. Identical alleles were found in genetically diverse isolates with no linkage disequilibrium, while the different MLST loci gave incongruent phylogenetic trees. This demonstrates that recombination is an important mechanism driving genetic variation in E. faecalis and suggests an epidemic population structure for E. faecalis. Our novel MLST scheme provides an excellent tool for investigating local and short-term epidemiology as well as global epidemiology, population structure, and genetic evolution of E. faecalis.

Alleles↗

PubMed2005

Evolution of transcription regulatory genes is linked to niche specialization in the bacterial pathogen Streptococcus pyogenes.

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of approximately 25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown.

Bacterial Proteins↗

PubMed2005

Evolutionary genetics of the accessory gene regulator (agr) locus in Staphylococcus aureus.

The accessory gene regulator (agr) locus influences the expression of many virulence genes in the human pathogen Staphylococcus aureus. Four allelic groups of agr, which generally inhibit the regulatory activity of each other, have been identified within the species. Interference in virulence gene expression caused by different agr groups has been suggested to be a mechanism for isolating bacterial populations and a fundamental basis for subdividing the species. To test the hypothesis that the species is phylogenetically structured according to agr groups, we mapped agr groups onto a clone phylogeny inferred from partial sequences of 14 genes from 27 genetically diverse strains. Shimodaira-Hasegawa and parametric bootstrap tests rejected the hypotheses that the species is subdivided into three or five monophyletic agr groups but failed to reject the hypothesis that the species is subdivided into two groups that each consist of multiple clonal complexes and multiple agr groups. Additional evidence for agr recombination is found from clustered polymorphisms in complete agr sequences. However, agr recombination has not occurred frequently or randomly through time, because the topology and branch lengths of the clone phylogeny are reflected within each agr group. To account for these observations, we propose a new evolutionary model that involves a genetically polymorphic ancestral population of S. aureus that horizontally transferred agr groups between two subspecies groups near the time that these subspecies groups diverged.

Bacterial Proteins↗

PubMed2005

Genetic background affects stability of mecA in Staphylococcus aureus.

The staphylococcal methicillin resistance determinant, mecA, resides on a mobile genetic element, staphylococcus chromosomal cassette mec (SCCmec). The distribution of SCCmec in nature is limited to relatively few clonal complexes of related methicillin-resistant Staphylococcus aureus (MRSA). We have previously reported that some genetic backgrounds are restrictive of mecA and penicillin-binding protein 2a expression, which could account for the restricted clonal distribution of SCCmec in nature. In this study, we investigate the potential role of the host chromosome in the transformability and expression of mecA in 103 naturally occurring methicillin-susceptible S. aureus clinical isolates. The isolates, which had been genotyped previously by multilocus sequence typing, were classified into one of two mutually exclusive categories based on whether the isolates belonged to "major" MRSA lineages or to "other" lineages that are never or occasionally MRSA. We introduced mecA expressed on the low-copy-number plasmid pYK20 into each MSSA strain and assayed the phenotype of resistance to nafcillin by population analysis to assess the relationship between the stability of mecA expression and genetic background. Strains from the major MRSA lineages were more transformable with pYK20 and better able to maintain the plasmid and express resistance in comparison to strains from other lineages. These data support the hypothesis that the presence of mecA within relatively few clonal complexes is partly due to genetic factors that are permissive of mecA and its gene product.

Bacterial Proteins↗

PubMed2005

Global spread of vancomycin-resistant Enterococcus faecium from distinct nosocomial genetic complex.

Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomycin-resistance gene (vanA) has crossed genus boundaries to methicillin-resistant Staphylococcus aureus. Spread of VRE, therefore, represents an immediate threat for patient care and creates a reservoir of mobile resistance genes for other, more virulent pathogens. Evolutionary genetics, population structure, and geographic distribution of 411 VRE and vancomycin-susceptible Enterococcus faecium isolates, recovered from human and nonhuman sources and community and hospital reservoirs in 5 continents, identified a genetic lineage of E. faecium (complex-17) that has spread globally. This lineage is characterized by 1) ampicillin resistance, 2) a pathogenicity island, and 3) an association with hospital outbreaks. Complex-17 is an example of cumulative evolutionary processes that improved the relative fitness of bacteria in hospital environments. Preventing further spread of this epidemic E. faecium subpopulation is critical, and efforts should focus on the early disclosure of ampicillin-resistant complex-17 strains.

Africa↗

PubMed2004

Evolutionary genetics of the capsular locus of serogroup 6 pneumococci.

The evolution of the capsular biosynthetic (cps) locus of serogroup 6 Streptococcus pneumoniae was investigated by analyzing sequence variation within three serotype-specific cps genes from 102 serotype 6A and 6B isolates. Sequence variation within these cps genes was related to the genetic relatedness of the isolates, determined by multilocus sequence typing, and to the inferred patterns of recent evolutionary descent, explored using the eBURST algorithm. The serotype-specific cps genes had a low percent G+C, and there was a low level of sequence diversity in this region among serotype 6A and 6B isolates. There was also little sequence divergence between these serotypes, suggesting a single introduction of an ancestral cps sequence, followed by slight divergence to create serotypes 6A and 6B. A minority of serotype 6B isolates had cps sequences (class 2 sequences) that were approximately 5% divergent from those of other serotype 6B isolates (class 1 sequences) and which may have arisen by a second, more recent introduction from a related but distinct source. Expression of a serotype 6A or 6B capsule correlated perfectly with a single nonsynonymous polymorphism within wciP, the rhamnosyl transferase gene. In addition to ample evidence of the horizontal transfer of the serotype 6A and 6B cps locus into unrelated lineages, there was evidence for relatively frequent changes from serotype 6A to 6B, and vice versa, among very closely related isolates and examples of recent recombinational events between class 1 and 2 cps serogroup 6 sequences.

Amino Acid Sequence↗

PubMed2004

Evolution of Staphylococcus aureus by large chromosomal replacements.

Conjugative transfer and replacement of hundreds of kilobases of a bacterial chromosome can occur in vitro, but replacements in nature are either an order of magnitude smaller or involve the movement of mobile genetic elements. We discovered that two lineages of Staphylococcus aureus, including a pandemic methicillin-resistant lineage, were founded by single chromosomal replacements of at least approximately 244 and approximately 557 kb representing approximately 10 and approximately 20% of the chromosome, respectively, without the obvious involvement of mobile genetic elements. The replacements are unprecedented in natural populations of bacteria because of their large size and unique structure and may have a dramatic impact on bacterial evolution.

Base Sequence↗

PubMed2003

Evolutionary models of the emergence of methicillin-resistant Staphylococcus aureus.

Five major lineages of methicillin-resistant Staphylococcus aureus (MRSA) have evolved since the introduction of methicillin for the treatment of infections caused by penicillin-resistant S. aureus in 1959. The clones of these lineages are responsible for the vast majority of hospital-acquired MRSA disease globally. We have constructed high-resolution evolutionary models for each lineage using a parsimony approach with 15 partial gene sequences from 147 geographically diverse isolates. On the basis of these models, we infer that MRSA has emerged at least 20 times upon acquisition of the methicillin resistance determinant, which is carried on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec). The acquisition of SCCmec by sensitive clones was four times more common than the replacement of one SCCmec with another. Notably, SCCmec type IV was found in twice as many clones as any other SCCmec type, and it is this SCCmec type which is commonly found in clones from patients with community-acquired MRSA disease. Our findings suggest that most clones of MRSA arise by the acquisition of SCCmec type IV by methicillin-sensitive isolates.

Amino Acid Sequence↗

PubMed2003

How clonal is Staphylococcus aureus?

Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable "core" genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.

Alleles↗

PubMed2002

The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries. We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, BURST, we analyzed an international collection of 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using BURST, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes. Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.

Alleles↗

PubMed2002

Evolution and virulence of serogroup 6 pneumococci on a global scale.

To study the evolution and virulence of pneumococcal populations, we used multilocus sequence typing to identify the major clones among 212 carriage and invasive isolates expressing capsular serogroup 6 from 39 countries. The global population consisted of 8 major complexes and 6 minor complexes of related clones and 32 clones of diverse origin. Surprisingly, serotype 6A clones evolved by mutation nearly as often as by recombination, whereas serotype 6B clones evolved almost exclusively by recombination (P = 0.0029). This is the first report of population genetic differences among serotypes of this species. The largest clonal complex was associated with invasive disease (P = 0.019) and included a common ancestor for five previously identified drug-resistant clones. The putative ancestors of the major clonal complexes were represented by a greater proportion of carriage isolates than were their descendents (P = 0.001), and the ancestors tended to be less virulent than their descendents in a mouse model of infection. These data suggested that virulent serogroup 6 clones have evolved multiple times from less-virulent ancestral clones.

Adolescent↗

PubMedDate not supplied

Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone.

During the 1950s, the notorious penicillin-resistant clone of Staphylococcus aureus known as phage type 80/81 emerged and caused serious hospital-acquired and community-acquired infections worldwide. This clone was largely eliminated in the 1960s, concurrent with the widespread use of penicillinase-resistant beta lactams. We investigated whether early 80/81 isolates had the genes for Panton-Valentine leucocidin, a toxin associated with virulence in healthy young people. Multilocus sequence analysis suggested that descendants of 80/81 have acquired meticillin resistance, are re-emerging as a community-acquired meticillin-resistant S aureus (MRSA) clone, and represent a sister lineage to pandemic hospital-acquired MRSA.

Australia↗