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Study Finds Small Genetic Changes Drive Evolution of ST-1 Group B Streptococcus

NEW YORK (GenomeWeb) – Whole-genome analysis of group B Streptococcus has revealed that a certain set of related and genetically highly similar strains of the bacteria are behind most adult infections in the US and Canada, researchers from the MD Anderson Cancer Center and elsewhere reported today in the Proceedings of the National Academy of Sciences.

The MD Anderson-led team collected nearly 230 serotype V group B Streptococcus strains from the blood of infected adults in the US and Canada between 1992 and 2013, and found that 92 percent of these strains were multilocus sequence type (ST) 1. GBS is an emerging cause of invasive disease in adults.

By sequencing a representative ST-1 strain, the researchers reported in PNAS that ST-1 is most similar to a GBS strain that infects mastitis. In addition, by comparing the sequences of various ST-1 strains, they noted that they are highly similar to one another and appear to undergo recombination infrequently, suggesting that small genetic changes drive the evolution of this disease.

"[W]e have discovered that the emergence of serotype V GBS-causing invasive disease in nonpregnant adults is primarily driven by ST-1 strains that are highly similar at the whole-genome level, but possess significant phenotypic diversity as a result of small genetic changes," MD Anderson's Samuel Shelburne and his colleagues wrote in their paper.

By sequencing a representative of the ST-1 strain using a combination of long Pacific Biosciences reads and paired-end Illumina short reads, the researchers assembled the strain genome and compared it to other GBS strains in the National Center for Biotechnology Information database. The strain was most closely related to a serotype V Swedish cow mastitis strain. The researchers reported the ST-1 GBS strain had more than 99 percent similarity to the mastitis strain and shared more than 99 percent of coverage, with the exception of a 40 kilobase region unique to the cow mastitis strain.

The ST-1 GBS strain itself had a unique gene located on a mobile genetic element that seemed to encode either a cell surface or secreted protein that could be linked to why this strain causes human disease, as it is lacking in non-ST-1 GBS strains. Shelburne and his colleagues dubbed this the AlpST-1 protein, as it resembles but appears distinct from, Alpha-like family proteins.

To gauge how the various ST-1 strains the researchers isolated are related to one another, they sequenced a further 201 ST-1 strains and compared them to the index strain at nearly 10,000 loci using two independent pipelines.

Eight strains showed greater phylogenetic divergence than the others, and these outlying strains exhibit signs of recombination with non-ST-1, non-serotype V GBS strains.

Despite that, Shelburne and his colleagues reported that recombination events otherwise appeared to occur infrequently in ST-1 strains.

The remaining 194 ST-1 strains the researchers sequenced were fairly similar to one another. More than 2,000 genes or 97 percent of the index strain genome was present in at least 192 of the 194 strains, indicating to the researchers that there are few differences in what genes are or are not present in the ST-1 strains. The core genome included the gene encoding the AlpST-1 protein, the researchers noted. Tetracycline-resistance genes were also common throughout ST-1 strains.

Further, Shelburne and his colleagues found that the average number of polymorphisms distinguishing any two ST-1 strains was 97, and that these differences seemed to be temporally, but not geographically, dependent.

Some 31 genes in the core ST-1 genome — including ones involved in polysaccharide capsule synthesis, pilus production regulation, and two-component gene regulatory systems — had significantly higher levels of genetic variations than other genes, indicating that they are undergoing adaptive evolution due to selective pressures.

The researchers also reported that strains with polymorphisms affecting known or suspected regulatory genes had distinctive transcriptomes. This, they said, underscores how small genetic variations can lead to significant phenotypic variations.

"These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans," Shelburne and his colleagues added.