1.C.84 The Subtilosin (Subtilosin) Family

Subtilosin A is an antimicrobial peptide produced by Bacillus subtilis. It possesses bactericidal activity against a diverse range of bacteria, including Listeria monocytogenes (Maqueda et al., 2008). Structural studies have found that subtilosin A is posttranslationally modified. It interacts with the lipid head group region of bilayer membranes, and at high concentrations, induces leakage from lipid bilayers. Subtilosin A adopts a partially buried orientation in lipid bilayers, inducing conformational changes in the lipid headgroups and disordering in the hydrophobic regions of bilayers. Lipid perturbation is the consequence of subtilosin A binding to lipid bilayers, which results in membrane permeabilization at high peptide concentrations (Thennarasu et al., 2005). Mutational variants of Subtilosin A with increased hemolytic activity have been isolated (Huang et al., 2009). 

The sactibiotic subclass of bacteriocins contain characteristic cysteine sulphur to α-carbon linkages mediated through post-translational modifications.  They include subtilosin, thuricinCD, thuricin H, and propionicin F (TC# 1.C.94).  Thuricin CD is a narrow spectrum anit-Clostridium difficile sactibiotic.  Others target Listeria monocytogenes, Gardnerella vaginalis and other pathogens (Mathur et al. 2015).

The generalized transport reaction believed to be catalyzed by sactibiotics is:

small molecules (in) → small molecules (out)



This family belongs to the Circular Bacterial Bacteriocin (CBB) Superfamily.

 

References:

Huang T., Geng H., Miyyapuram VR., Sit CS., Vederas JC. and Nakano MM. (2009). Isolation of a variant of subtilosin A with hemolytic activity. J Bacteriol. 191(18):5690-6.

Maqueda, M., M. Sánchez-Hidalgo, M. Fernández, M. Montalbán-López, E. Valdivia, M. Martínez-Bueno. (2008). Genetic features of circular bacteriocins produced by Gram-positive bacteria. FEMS Microbiol. Rev. 32(1):2-22.

Mathur, H., M.C. Rea, P.D. Cotter, C. Hill, and R.P. Ross. (2015). The sactibiotic subclass of bacteriocins: an update. Curr. Protein. Pept. Sci. 16: 549-558.

Thennarasu, S., D.K. Lee, A. Poon, K.E. Kawulka, J.C. Vederas, and A. Ramamoorthy. (2005). Membrane permeabilization, orientation, and antimicrobial mechanism of subtilosin A. Chem. Phys. Lipids. 137(1-2):38-51.

Examples:

TC#NameOrganismal TypeExample
1.C.84.1.1

Leakage-promoting cyclic peptide, Subtilosin (43aas)

Gram-positive bacteria

Subtilosin of Bacillus subtilis (O07623)

 
1.C.84.1.2

Subilosin A

Firmicutes

Subtilosin A of Streptococcus constellatus (Gemella morbillorum)