The Non-Lantibiotic Bacteriocin Garvicin Q Targets Man-PTS in a Broad Spectrum of Sensitive Bacterial Genera

Aleksandra Tymoszewska,Paulina Wirtek,Dzung B Diep,Tamara Aleksandrzak-Piekarczyk

doi:10.1038/s41598-017-09102-7

Abstract

Mannose phosphotransferase system (Man-PTS) is the main mannose permease in bacteria but it is also a known receptor for subclass IIa bacteriocins (pediocin-like group) as well as subclass IId lactococcin A (LcnA) and lactococcin B (LcnB) (LcnA-like group). Subclass IIa bacteriocins exhibit a strong activity against Listeria spp. but they are not against Lactococcus spp. In contrast, the LcnA-like bacteriocins act only against Lactococcus lactis strains. Garvicin Q (GarQ) is a subclass IId bacteriocin with minor similarity to LcnA-like bacteriocins and a relatively broad antimicrobial spectrum including, among others, Listeria and Lactococcus spp. To identify the GarQ receptor, we obtained GarQ-resistant mutants of Lactococcus garvieae IBB3403 and L. lactis IL1403 and sequenced their genomes that revealed mutations in genes encoding the membrane-bound Man-PTS IIC or IID subunits encoded by ptnCD in L. lactis and manCD in L. garvieae. This is the first time that a bacteriocin outside the pediocin- and LcnA-like groups is shown to target Man-PTS. The interaction between GarQ and Man-PTS may occur through a new binding pattern involving specific amino acids highly conserved among the GarQ-sensitive bacterial species located in the N-terminal part and extracellular loops of subunit IID and in transmembrane region of IIC.

Highlights

The bacteriocins differ from each other by their inhibitory spectra, each targeting a defined set of bacteria, which suggests that they recognize specific receptors on the target cells[6]
We experimentally identify the amino acids of Mannose phosphotransferase system (Man-PTS) from L. lactis and L. garvieae potentially responsible for Garvicin Q (GarQ) binding and show that they are not involved in the binding of lactococcin A (LcnA)-group bacteriocins
Like other bacteriocins produced by Gram-positive bacteria, they can be used to combat certain infections caused by Gram-positive pathogens other than L. garvieae

Summary

Introduction

The bacteriocins differ from each other by their inhibitory spectra, each targeting a defined set of bacteria, which suggests that they recognize specific receptors on the target cells[6]. Studies showed that Man-PTS, apart from its principal sugar-transporter function, could serve as a receptor for subclass IIa bacteriocins. Region α is indispensable for specific binding of subclass IIa bacteriocins and has been found to be present in the sensitive L. monocytogenes strains and absent in the resistant L. lactis strains. A distinct spectrum of activity has been observed for Man-PTS-targeting subclass IId bacteriocins LcnA and LcnB active only against L. lactis species[18]. GarQ is a subclass IId bacteriocin produced by Lactococcus garvieae BCC 43578 isolated from fermented-pork sausage[19]. It uses a so called double-glycine leader for secretion and the mature peptide is 50 amino acids long. Despite lacking the YGNGVXC motif characteristic for pediocin-like bacteriocins, GarQ is active against L. monocytogenes[19]

Methods

Results

Conclusion