Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

Abstract

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

Keywords: Gram-negative bacteria; Gram-positive bacteria; antimicrobial activities; bacteriocins; multidrug-resistant bacteria.

Figure 1

Classification of bacteriocins produced by Gram-positive (A) and Gram-negative (B) bacteria.

Figure 2

Structures of some unusual amino acids retrieved in bacteriocins produced by Gram-positive bacteria.

Figure 3

Transport mechanisms involved in the export of BGPB (A) and BPGN (B) from the producer strain.

Figure 4

Mechanisms of action of nisin and lactococcin A. (A) By targeting lipid II, nisin can inhibit peptidoglycan biosynthesis and form pores in the bacterial membrane. (B) Lactococcin A uses the mannose phosphotransferase system (Man-PTS) as a receptor, leading to uncontrolled opening of this receptor and thereby forming a pore in the bacterial membrane.

Figure 5

Mechanisms of microcins’ entry inside sensitive bacterial strains and their inner membrane (A) and intracellular (B) targets.

Figure 6

Structure of microcin C precursor and site of cleavage by deformylase (1), aminopeptidases enzymes (2) and serine proteases (3). Microcin C is double processed in bacterial targeted cells, first by deformylase and then by specific aminopeptidase, releasing the active microcin C which is an aspartyl-AMP analogue that competes with this natural substrate and inhibits tRNA-synthetase in sensitive strains. Specific serine proteases can deactivate microcin C in some resistant strains.

Figure 7

Colicin A entry inside sensitive bacterial strains. Colicin A first binds to the ButB outer membrane receptor and then uses the OmpF translocator to cross the outer membrane. Colicin A is then guided by the TolA-Pal system and its pore-forming domain is inserted into the inner membrane.

Figure 8

Self- immunity and transport mechanisms of mersacidin (A) and lactoccocin A (B) that target lipid II and Man-PTS, respectively. Proteins employed for self-immunity and transport of these bacteriocins are distinct and encoded by different genetic elements, as presented.