Streptococcus mutans, a dental pathogen, secretes different kinds of lantibiotic 
and nonlantibiotic bacteriocins. For self-protection, a bacteriocin producer 
strain must possess one or more cognate immunity mechanisms. We report here the 
identification of one such immunity complex in S. mutans strain GS-5 that 
confers protection against Smb, a two-component lantibiotic. The immunity 
complex that we identified is an ABC transporter composed of two proteins: SmbF 
(the ATPase component) and SmbT (the permease component). Both of the 
protein-encoding genes are located within the smb locus. We show that GS-5 
becomes sensitized to Smb upon deletion of smbT, which makes the ABC transporter 
nonfunctional. To establish the role SmbFT in providing immunity, we 
heterologously expressed this ABC transporter complex in four different 
sensitive streptococcal species and demonstrated that it can confer resistance 
against Smb. To explore the specificity of SmbFT in conferring resistance, we 
tested mutacin IV (a nonlantibiotic), nisin (a single peptide lantibiotics), and 
three peptide antibiotics (bacitracin, polymyxin B, and vancomycin). We found 
that SmbFT does not recognize these structurally different peptides. We then 
tested whether SmbFT can confer protection against haloduracin, another 
two-component lantibiotic that is structurally similar to Smb; SmbFT indeed 
conferred protection against haloduracin. SmbFT can also confer protection 
against an uncharacterized but structurally similar lantibiotic produced by 
Streptococcus gallolyticus. Our data suggest that SmbFT truly displays immunity 
function and confer protection against Smb and structurally similar 
lantibiotics.