A single system detects and protects the beneficial oral bacterium Streptococcus sp. A12 from a spectrum of antimicrobial peptides

Abstract

The commensal bacterium Streptococcus sp. A12 has multiple properties that may promote the stability of health-associated oral biofilms, including overt antagonism of the dental caries pathogen Streptococcus mutans. A LanFEG-type ABC transporter, PcfFEG, confers tolerance to the lantibiotic nisin and enhances the ability of A12 to compete against S. mutans. Here, we investigated the regulation of pcfFEG and adjacent genes for a two-component system, pcfRK, to better understand antimicrobial peptide resistance by A12. Induction of pcfFEG-pcfRK was the primary mechanism to respond rapidly to nisin. In addition to nisin, PcfFEG conferred tolerance by A12 to a spectrum of lantibiotic and non-lantibiotic antimicrobial peptides produced by a diverse collection of S. mutans isolates. Loss of PcfFEG resulted in the altered spatiotemporal arrangement of A12 and S. mutans in a dual-species biofilm model. Deletion of PcfFEG or PcfK resulted in constitutive activation of pcfFEG and expression of pcfFEG was inhibited by small peptides in the pcfK mutant. Transcriptional profiling of pcfR or pcfK mutants combined with functional genomics revealed peculiarities in PcfK function and a novel panel of genes responsive to nisin. Collectively, the results provide fundamental insights that strengthen the foundation for the design of microbial-based therapeutics to control oral infectious diseases.

Synthesis of a Novel Lantibiotic Using Mutacin II Biosynthesis Apparatus

“…However, in a previous study, we showed that the immunity protein SmbFT of a two-peptide mutacin, SmbAB, can also recognize two other closely related two-peptide lantibiotics, haloduracin and gallolacticin, to provide protection ( 25 ). Furthermore, the MutFEG-type immunity complex is also known to provide protection broadly ( 50 ). Thus, immunity function might not be an issue for our system of expressing the type A-II class of lantibiotics.…”

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

“…A12. The results indicated that a novel set of genes (e.g., dipeptidase-PrsW-like protease, Ccma ABC transporter, and Man-PTS) was responsible for nisin resistance [46]. With respect to Listeria monocytogenes, a transposon library was used to identify transposants with significantly altered biofilm production levels when compared to a wild-type strain.…”

Anti‐caries Streptococcus spp.: A potential preventive tool for special needs patients

“…68 The resistance to antimicrobial peptides has recently been attributed to the regulation of the transporter gene PcfFEG, which improves the ability of S. A12 to compete with S. mutans. 69 Shields et al 70 designed a tool that allows for the monitoring of bacterial growth and the bacterial interaction in situ, differentiating among various bacteria that constitute the oral cavity biofilm. The number of S. mutans colonies after 72 h of monoculture was significantly larger than that of the cocultures with S. gordonii and S. A12.…”

“…The resistance to antimicrobial peptides has recently been attributed to the regulation of the transporter gene PcfFEG, which improves the ability of S . A12 to compete with S. mutans 69 …”