Probing the role of heterogeneity in streptococcal interactions - PROJECT SUMMARY/ABSTRACT
Streptococci are the most abundant microbes in the human oral cavity, with most people harboring multiple
species, and often even multiple strains of the same species (1-6). Further, while most species of oral
streptococci are not pathogenic, studies with selected strains have shown that streptococci can influence the
physical location and the virulence factor expression of oral pathogens such as Porphyromonas gingivalis (Pg),
Aggregatibacter actinomycetemcomitans (Aa), and Fusobacterium nucleatum (2, 3, 7-11). These interactions
influence the progression and severity of disease, as well as its resistance to treatment (7, 12-16). However,
these interactions also rely are governed by the traits that are known to vary across the genus, such as cell
surface structures and secreted organic acids (17, 18). Further, transcriptional heterogeneity resulting in the
existence of subpopulations, can further alter the behavior of streptococci (19-23). Thus, while the abundant
streptococcal genus is thought of as an important mediator of pathogen behavior, it is not well understood how
streptococcal-pathogen interactions vary across the genomic and transcriptomic diversity of the genus. In this
study, the overarching hypothesis is that genomic, phenotypic, and transcriptional heterogeneity of commensal
streptococci alters interactions with pathogens and impacts infections. This proposal aims to expand our
understanding of streptococcal-pathogen interactions by investigating diversity at two levels: genomic and
transcriptional. First, it proposes to systematically characterize the interactions formed by taxonomically diverse
streptococci with the pathogens Pg and Aa in a phylogenomic framework (Aim 1). This work will identify the scale
at which interactions vary across the streptococcal genus and potentially identify new functions that mediate
interactions with these pathogens. Second, this proposal will characterize the transcriptional heterogeneity in
commensal streptococci that result in subpopulations and ask how subpopulations influence, and are influenced
by, interactions with oral pathogens (Aim 2). This aim will significantly advance our understanding of the role of
transcriptional heterogeneity in oral commensal streptococci, how it varies taxonomically, and how it is altered
by environmental changes. Further, both Aims will consider the interplay of streptococcal diversity and
interactions on spatial patterning at the micron-level. Overall, the proposed research will broaden our
understanding of the role of streptococci during oral disease.
