Injectosomes in Gram-Positive Bacteria

Gram-positive bacteria are enclosed by a single membrane and therefore have apparently not evolved or acquired secretion systems similar to the type I, III, and IV systems found in the gram-negative bacteria. Although type III and IV systems are not found in gram-positive bacterial pathogens, these pathogens still translocate effectors into eukaryotic cells. This chapter examines the structure-function aspects of the cholesterol-dependent cytolysins (CDCs) and how the CDC mechanism has been adapted for use by Streptococcus pyogenes to form its injectosome. The most recognizable feature of the CDC primary structure is the conserved undecapeptide that is located near the carboxy terminus of the CDCs. The CDCs are highly soluble proteins once released from the secretion system of the bacterial cell; and they undergo a remarkable transition that results in their conversion from soluble molecules into a supramolecular pore-forming membrane complex. The S. pyogenes injectosome is composed of two known components, SLO and the Sec-dependent secretion pathway; in combination, they are necessary for the translocation of the NAD+ glycohydrolase (SPN) from S. pyogenes into the cytoplasm of human keratinocytes. SPN is a 52-kDa protein that contains a typical signal peptide for a Sec-dependent protein and is found in the supernatant of cultured organisms. No SPN-related enzymes have been identified in other gram-positive bacteria, and SPN is not structurally related to any known protein. The injectosome of S. pyogenes is a paradigm that will impact several areas of biology because of the many interesting questions posed by this system.