1.C.41 The Tripartite Haemolysin BL (HBL) Family

The HBL family includes a tipartite haemolysin from Bacillus cereus (Beecher and Wong 2000). The three components are homologous but distantly related to each other. They are called HBL component B, HBL component L1 and HBL component L2. The toxin forms pores and has also been called the enterotoxic, necrotizing, vascular, permeability toxin, a likely virulence factor of B. cereus diarrheal food poisoning and necrotic infections (Sastalla et al. 2013). Two distinct sets of all three HBL components have been isolated from a single B. cereus isolate, MGBC145. Both exhibit haemolytic and vascular permeability activities, and the homologues could function interchangeably. In addition to B. cereus, a homologue, called Haemolysin YhlA has been isolated and characterized from Edwardsiella tarda (Chen et al. 1996).

Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Fox et al. 2020 showed non-haemolytic enterotoxin (NHE) from the human foodborne pathogen, Bacillus cereus, is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative TMS, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunits B and A, thus forming a tripartite lytic pore that allows efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome (Fox et al. 2020).

The generalized transport reaction catalyzed by HBL is:

Solutes (in) ⇌ solutes (out)