The Role of Gram-Positive Surface Proteins in Bacterial Niche- and Host-Specialization

Gram-positive bacterial pathogens have an array of proteins on their cell surface that mediate interactions with the hostenvironment. In particular, bacterial cell wall-associated (CWA) proteins play key roles in both colonization and pathogenesis.Furthermore, some CWA proteins promote specialization for host-species or mediate colonization of specific anatomical nicheswithin a host. In this mini review, we provide examples of the many ways by which major pathogens, such as Staphylococci,Streptococci and Listeria monocytogenes, utilize CWA proteins for both host- and niche-specialization. We describe differentbiological mechanisms mediated by CWA proteins including: the acquisition of iron from hemoglobin in the bloodstream, adherence to and invasion of host cells, and innate immune evasion through binding to the plasma proteins fibrinogen, immunoglobulin G, and complement. We also discuss the limitations of using animal models for understanding the role of specific CWA proteins in host-specialization and how transformative technologies, such as CRISPR-Cas, offer tremendous potential for developing transgenic models that simulate the host environment of interest. Improved understanding of the role of CWA proteins in niche- or host-specificity will allow the design of new therapeutic approaches which target key host-pathogen interactions underpinningGram-positive bacterial infections