Secretin pilot protein MxiM (MxiM) (MxiM)

MxiM is a specialized lipoprotein, categorized as a pilotin, that is essential for the assembly of the Type III secretion system (T3SS) in Shigella flexneri (UniProt: P0A204). Its primary biological function is to facilitate the proper localization and insertion of the secretin protein, MxiD, into the bacterial outer membrane (Lario et al., 2005). MxiM binds to the C-terminal S-domain of MxiD within the periplasm and guides it to the outer membrane, likely utilizing the Lol (localization of lipoprotein) pathway (Okuda et al., 2009). In the absence of MxiM, the MxiD secretin fails to form the multimeric pore-like structure required for the T3SS apparatus, leading to the degradation of MxiD and a complete loss of virulence (Schuch & Maurelli, 1997). Because the T3SS is the primary mechanism by which Shigella invades human intestinal epithelial cells to cause shigellosis, MxiM is considered a high-value target for novel antivirulence drugs. Inhibiting MxiM or its interaction with MxiD offers a strategy to disarm the pathogen without directly killing it, potentially reducing the selective pressure for antibiotic resistance (McDonough et al., 2021). This approach is particularly relevant given the increasing prevalence of multi-drug resistant Shigella strains globally. Research into small molecule inhibitors that disrupt the MxiM-MxiD interface is ongoing as a method to treat bacillary dysentery.

Other names

Lipoprotein MxiMPilotin MxiMMxiM lipoprotein

Disruption of the MxiM-MxiD interaction to prevent the assembly of the Type III secretion system secretin pore, thereby attenuating bacterial virulence.