SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
We report the complete genome sequences of 38 Streptococcus sanguinis genomes, isolated from human oral and endocarditis-associated samples. These genomes are each comprised of a single chromosome that ranges from approximately 2.29 to 2.48 Mb in length, with an average GC content of 43.2%.
Streptococci may enter a physiological state called competence, during which they express a specific set of genes required for exogenous DNA uptake and its subsequent integration into the genome through homologous recombination. This process, termed natural transformation, facilitates the horizontal acquisition of genetic material, potentially conferring adaptive advantages that enhance bacterial survival under selective pressures. To make homologous DNA available in the surrounding environment, Streptococcus pneumoniae expresses a cell wall hydrolase (CbpD) that lyses and kills closely related species. This process has been coined fratricide, and the acting hydrolase a fratricin. A significant fraction of streptococcal species does not encode a CbpD-like protein, but another competence-induced peptidoglycan hydrolase LytF. It has been speculated that LytF serves the same purpose as CbpD, however, our investigations into the role of LytF in Streptococcus sanguinis revealed no evidence supporting LytF as a fratricin. Instead, we show that LytF is involved in natural transformation by promoting DNA uptake. An essential part of DNA uptake is the competence-induced type IV pilus, which facilitates DNA uptake by pulling nearby DNA toward the cell. By immunoblotting and microscopy imaging, we found that LytF increases the extracellular levels of the major pilus component ComGC, suggesting that LytF may modify peptidoglycan to promote pilus extrusion across the cell wall, thereby enhancing the efficiency of DNA uptake.
Infective endocarditis (IE) is a life-threatening disease most often caused by blood-borne bacteria that infect previously damaged cardiac tissue. Despite the importance of this disease, the genetic basis for IE-associated fitness remains poorly defined. Here, we present the first genome-wide in vivo analysis of bacterial fitness in a vertebrate model of IE. We identified 146 genes in Streptococcus sanguinis required for IE fitness, the majority of which had not previously been linked to endocarditis. These determinants cluster into conserved metabolic, cell envelope, transport, and regulatory pathways, representing a vast reservoir of potential targets for novel antimicrobial intervention. A subset of these genes was examined in Streptococcus mutans; all were found to be essential for IE fitness in this distantly related oral species as well, suggesting broad conservation. Using experimental evolution, we further show that disruption of key fitness pathways triggers reproducible compensatory "bypass" mechanisms. Together, these findings provide a comprehensive, genome-wide map of the bacterial niche-requirements for streptococcal infective endocarditis.