Biomedical subjects

Brian G Spratt

Publications and source records attributed to Brian G Spratt.

3 recordsLinked to original sources

PubMed2005

Fuzzy species among recombinogenic bacteria.

BACKGROUND: It is a matter of ongoing debate whether a universal species concept is possible for bacteria. Indeed, it is not clear whether closely related isolates of bacteria typically form discrete genotypic clusters that can be assigned as species. The most challenging test of whether species can be clearly delineated is provided by analysis of large populations of closely-related, highly recombinogenic, bacteria that colonise the same body site. We have used concatenated sequences of seven house-keeping loci from 770 strains of 11 named Neisseria species, and phylogenetic trees, to investigate whether genotypic clusters can be resolved among these recombinogenic bacteria and, if so, the extent to which they correspond to named species. RESULTS: Alleles at individual loci were widely distributed among the named species but this distorting effect of recombination was largely buffered by using concatenated sequences, which resolved clusters corresponding to the three species most numerous in the sample, N. meningitidis, N. lactamica and N. gonorrhoeae. A few isolates arose from the branch that separated N. meningitidis from N. lactamica leading us to describe these species as 'fuzzy'. CONCLUSION: A multilocus approach using large samples of closely related isolates delineates species even in the highly recombinogenic human Neisseria where individual loci are inadequate for the task. This approach should be applied by taxonomists to large samples of other groups of closely-related bacteria, and especially to those where species delineation has historically been difficult, to determine whether genotypic clusters can be delineated, and to guide the definition of species.

Cluster Analysis↗

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

Influence of recombination and niche separation on the population genetic structure of the pathogen Streptococcus pyogenes.

The throat and skin of the human host are the principal reservoirs for the bacterial pathogen Streptococcus pyogenes. The emm locus encodes structurally heterogeneous surface fibrils that play numerous roles in virulence, depending on the strain. Isolates harboring the emm pattern A-C marker exhibit a strong tendency to cause throat infection, whereas emm pattern D strains are usually recovered from impetigo lesions; as a group, emm pattern E organisms fail to display obvious tissue tropisms. The peak incidence for streptococcal pharyngitis and impetigo varies with season and locale, leading to wide spatial and temporal distances between throat and skin strains. To assess any impact of niche separation on genetic variation, the extent of recombinational exchange between emm pattern A-C, D, and E subpopulations was evaluated. Analysis of nucleotide sequence data for internal portions of seven housekeeping loci from 212 isolates provides evidence of extensive recombination between strains belonging to different emm pattern subpopulations. Furthermore, no fixed nucleotide differences were found between emm pattern A-C and D strains. Thus, despite some niche separation created by distinct epidemiological trends and innate tissue tropisms there is little evidence for neutral gene divergence between throat and skin strains. Maintenance of a relationship between emm pattern and tissue tropism in the face of underlying recombination suggests that tissue tropism is associated with emm or a closely linked gene.

Alleles↗