Streptococcus pneumoniae two-component regulatory systems: The interplay of the pneumococcus with its environment

Streptococcus pneumoniae is a human pathobiont possessing a diverse array of multifunctional proteins essential for bacterial fitness and virulence. Gene expression is tightly controlled by regulatory components and among the pneumococcal sensorial tools, two‑component regulatory systems (TCS) are the most widespread and conserved. This review aims to provide a comprehensive analysis of original studies on pneumococcal TCS on a functional level. Despite a rather chaotic nomenclature, the current available information on pneumococcal regulation by these systems can be conveniently addressed, according to the regulation of pathophysiological cell processes and the responses to detectable environmental signals. Pneumococcal pathophysiological processes driven by TCS can be further categorized into competence and fratricide, bacteriocin production, and virulence factors expression. Conversely, detectable environmental signals by pneumococci can be grouped into antibiotics and cell wall perturbations, environmental stress, and nutrients acquisition. This review summarizes the state of the art on pneumococcal TCS based on an integral approach and thus providing insights into the regulatory network(s) of S. pneumoniae.