Type VIIb secretion systems in Lactobacillales: insights from streptococci and enterococci
ABSTRACT The type VII secretion system (T7SS) is an ATPase-powered molecular machine encoded by Actinomycetota (T7SSa) and Bacillota (T7SSb) that exports small alpha-helical effectors with functions in interbacterial competition, host colonization, and virulence. While T7SSb has been well characterized in Staphylococcus aureus and Bacillus subtilis, its presence and function within the order Lactobacillales have only been thoroughly investigated within the past decade. Experimental evidence for T7SSb function has now been established in select Streptococcus and Enterococcus species. Here, we review the current understanding of T7SSb in these genera, covering core machinery and secreted substrates, including LXG toxins and WXG100 proteins. We discuss the roles of T7SSb during interbacterial antagonism and host-pathogen interactions, including contributions to cytotoxicity and virulence, as well as mucosal colonization and persistence. We further review known regulators of the T7SSb and evaluate the ecological significance of T7SSb-mediated competition for microbial community stability. Finally, we highlight outstanding questions in the field, including mechanisms of effector delivery, structural determination of the apparatus, impact of effectors on host immunity, and potential therapeutic targeting of T7SSb components.