Staphylococcins: an update on antimicrobial peptides produced by staphylococci and their diverse potential applications.

Staphylococcins are antimicrobial peptides or proteins produced by staphylococci. They can be separated into different classes, depending on their amino acid composition, structural complexity, and steps involved in their production. In this review, an overview of the current knowledge on staphylococcins will be presented with emphasis on the information collected in the last decade, including a brief description of new peptides. Most staphylococcins characterized to date are either lantibiotics or linear class II bacteriocins. Recently, gene clusters coding for production of circular bacteriocins, sactipeptides, and thiopeptides have been mined from the genome of staphylococcal isolates. In contrast to class II bacteriocins, lantibiotics, sactipeptides, and thiopeptides undergo post-translational modifications that can be quite extensive, depending on the peptide. Few staphylococcins inhibit only some staphylococcal species, but most of them have proven to target pathogens belonging to different genera and involved in a variety of infectious diseases of clinical or agronomic importance. Therefore, these peptides exhibit potential application as anti-infective drugs in different areas. This review will also cover this diverse and remarkable potential. To be commercialized, however, staphylococcin production should be cost-effective and result in high bacteriocin yields, which are not generally achieved from the culture supernatant of their native producers. Such low yields make their production quite costly and not suitable at large industrial scale. Efforts already made to overcome this limitation, minimizing costs and time of production of some staphylococcins and employing either chemical synthesis or in vivo biosynthesis, will be addressed in this review as well. KEY POINTS: • Staphylococci produce a variety of antimicrobial peptides known as staphylococcins. • Most staphylococcins are post-translationally modified peptides. • Staphylococcins exhibit potential biotechnological applications. Graphical abstract.

Molecular characterization of aureocin 4181: a natural N-formylated aureocin A70 variant with a broad spectrum of activity.

Bacteriocins are ribosomally synthesized antimicrobial peptides produced by prokaryotes. Here, the molecular characterization of aureocin 4181, a bacteriocin produced by Staphylococcus aureus 4181, a strain involved in bovine mastitis, is presented. Aureocin 4181 gene cluster (aurRID1CBAT) was mined from scaffold 15 of the draft genome of its producer strain. Three (AurABC) out of the four structural peptides of aureocin 4181 are identical to those of aureocin A70, except for AurD1 of aureocin 4181, which showed a conservative substitution of Leu29 to Phe29 when compared to AurD of aureocin A70. According to molecular mass determination and peptide sequencing, combined with genome sequencing data, aureocin 4181 is an N-formylated variant of aureocin A70. The analysis of its antimicrobial spectrum was extended to include strains of the two major contagious pathogens involved in bovine mastitis, S. aureus and Streptococcus agalactiae. Aureocin 4181 exhibited a striking activity against S. aureus, inhibiting most strains tested. Besides having a broader spectrum of activity, aureocin 4181 exhibited a stronger bacteriolytic action against the target strains and proved to be from two- to fourfold more active than aureocin A70 against S. aureus. Aureocin 4181 has potential to become an alternative drug for prevention and control of mastitic staphylococci, a pathogen that imposes a huge economic burden to dairy industry worldwide. It also represents the third four-component bacteriocin described in the literature, the second in staphylococci.

Bacterial Labionin-Containing Peptides and Sactibiotics: Unusual Types of Antimicrobial Peptides with Potential Use in Clinical Settings (a Review).

One of the biggest challenges faced presently by clinicians is the emergence of multidrug -resistant pathogens that can infect humans and animals. To control the infections caused by such pathogens the development of new drugs is required. Bacteria are a rich source of ribosomally -synthesized antimicrobial peptides known as bacteriocins, which are characterized by the presence of a self-defense immunity system. Labionin-containing lantibiotics and sactibiotics are posttranslationally modified bacteriocins with peculiar features. Labionin-containing peptides belong to subclass Ic lantibiotics in which the carbacyclic triamino triacid labionin, a structural variant of lanthionine, and a methyl-substitute labionin derivative are found, giving the molecule a labyrinthine structure. Sactibiotics are circular or linear peptides belonging to a distinct bacteriocin class (class V) which is characterized by the presence of cross-linkages formed by the thiol group of cysteine residues and the α-carbon of acceptor amino acids. A few examples of these bacteriocins have been described in the literature to date, although putative gene clusters with the potential to encode such peptides can be found in the genome of many bacterial species. Some peptides already under study exhibit potential biotechnological applications because of their remarkable antibacterial or antiviral activities, as well as their analgesic activity. Therefore, in this review, the main findings concerning these peptides will be addressed and discussed, with an emphasis on their potential use in clinical settings.

Mobilization functions of the bacteriocinogenic plasmid pRJ6 of Staphylococcus aureus.

Plasmid pRJ6 is the first known bacteriocinogenic mobilizable (Mob) plasmid of Staphylococcus aureus. Its Mob region is composed of four mob genes (mobCDAB) arranged as an operon, a genetic organization uncommon among S. aureus Mob plasmids. oriT (pRJ6) was detected in a region of 431 bp, positioned immediately upstream of mobC. This region, when cloned into pCN37, was able to confer mobilization to the re-combinant plasmid only in the presence of pRJ6. The entire Mob region, including oriT (pRJ6), is much more similar to Mob regions from several coagulase-negative staphylococci plasmids, although some remarkable similarities with S. aureus Mob plasmids can also be noted. These similarities include the presence within oriT (pRJ6) of the three mcb (MobC binding sites), firstly described in pC221 and pC223, an identical nick site also found in these same plasmids, and a nearly identical sra(pC223) site (sequence recognized by MobA). pRJ6 was successfully transferred to S. epidermidis by conjugation in the presence of the conjugative plasmid pGOl. Altogether these findings suggest that pRJ6 might have been originally a coagulase-negative staphylococci plasmid that had been transferred successfully to S. aureus.

Activity of staphylococcal bacteriocins against Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis.

The inhibitory activity of seven bacteriocins produced by Staphylococcus aureus (aureocins A70, A53, and 215FN) and Staphylococcus epidermidis (Pep5, epidermin, epilancin K7 and epicidin 280) was tested against strains of both S. aureus (165 strains) and Streptococcus agalactiae (74 strains) isolated from udders of cows suffering from bovine mastitis. Most strains of the two species were inhibited by epidermin (>85%), aureocin A53 (>67%) and by a combination of aureocins A70 and A53 (>91%), co-expressed in the genetic background of strain A70, the native producer of aureocin A70. Synergy between aureocins A70 and A53 was also demonstrated, which broadened the spectrum of strains inhibited. The remaining staphylococcins inhibited either none of, or a lower percentage (<48%) of, the mastitis-causing pathogens tested. Our results therefore show that the use of epidermin and/or a combination of aureocins A53 and A70 may represent a new non-antibiotic alternative for successfully inhibiting both mastitic staphylococci and streptococci.