title: A conserved streptococcal membrane protein, LsrS, exhibits a receptor-like function for lantibiotics.
abstract: Streptococcus mutans strain GS-5 produces a two-peptide lantibiotic, Smb, which displays inhibitory activity against a broad spectrum of bacteria, including other streptococci. For inhibition, lantibiotics must recognize specific receptor molecules present on the sensitive bacterial cells. However, so far no such receptor proteins have been identified for any lantibiotics. In this study, using a powerful transposon mutagenesis approach, we have identified in Streptococcus pyogenes a gene that exhibits a receptor-like function for Smb. The protein encoded by that gene, which we named LsrS, is a membrane protein belonging to the CAAX protease family. We also found that nisin, a monopeptide lantibiotic, requires LsrS for its optimum inhibitory activity. However, we found that LsrS is not required for inhibition by haloduracin and galolacticin, both of which are two-peptide lantibiotics closely related to Smb. LsrS appears to be a well-conserved protein that is present in many streptococci, including S. mutans. Inactivation of SMU.662, an LsrS homolog, in S. mutans strains UA159 and V403 rendered the cells refractory to Smb-mediated killing. Furthermore, overexpression of LsrS in S. mutans created cells more susceptible to Smb. Although LsrS and its homolog contain the CAAX protease domain, we demonstrate that inactivation of the putative active sites on the LsrS protein has no effect on its receptor-like function. This is the first report describing a highly conserved membrane protein that displays a receptor-like function for lantibiotics.
authors: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors: Saswati
authors: S
authors: Biswas
authors: Indranil
authors: I
authors: Biswas
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001430:Bacteriocins / Q000378:metabolism*; D004251:DNA Transposable Elements; D017353:Gene Deletion; D015870:Gene Expression; D008565:Membrane Proteins / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D011485:Protein Binding; D013295:Streptococcus mutans / Q000235:genetics / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D004251:DNA Transposable Elements; D008565:Membrane Proteins