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

Abstract

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 Leu 29 to Phe 29 when compared to AurD of aureocin A70. According to molecular mass determination and peptide sequencing, combined with genome sequencing data, aureocin 4181 is an Nformylated 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.

Comparative genomic analysis of Staphylococcus aureus isolates associated with either bovine intramammary infections or human infections demonstrates the importance of restriction-modification systems in host adaptation

“…Aureocin 4181 is known to exhibit strong antimicrobial activity against isolates of Micrococcus luteus , Streptococcus agalactiase , S. aureus , and other staphylococci [69]. This bacteriocin may modify the microbial composition of the udder skin and teat canal thus disturbing the native microbiome.…”

“…Indeed, we previously confirmed that CC151 ( agr type II) inhibited the quorum-sensing of CC97 ( agr type I) in co-culture conditions [ 60 ]. The pCC97-1 plasmid, which is most homologous to pRJ80 plasmid with 99.78 % identity, was found in CC97 isolates and encoded genes for aureocin 4181 products: aureocin peptides, known as heat-stable bacteriocins, bacteriocin immunity protein, bacteriocin regulatory protein, and bacteriocin exporter protein [ 69 ]. Aureocin 4181 is known to exhibit strong antimicrobial activity against isolates of Micrococcus luteus , Streptococcus agalactiase , S. aureus , and other staphylococci [ 69 ].…”

“…The pCC97-1 plasmid, which is most homologous to pRJ80 plasmid with 99.78 % identity, was found in CC97 isolates and encoded genes for aureocin 4181 products: aureocin peptides, known as heat-stable bacteriocins, bacteriocin immunity protein, bacteriocin regulatory protein, and bacteriocin exporter protein [ 69 ]. Aureocin 4181 is known to exhibit strong antimicrobial activity against isolates of Micrococcus luteus , Streptococcus agalactiase , S. aureus , and other staphylococci [ 69 ]. This bacteriocin may modify the microbial composition of the udder skin and teat canal thus disturbing the native microbiome.…”

Comprehensive Approaches for the Search and Characterization of Staphylococcins

“…As for bacteriocin production, several staphylococcins have been reported among staphylococci of livestock ( Table 1 and Table 2 ), frequently in those recovered from bovine mastitis (Aureocin 4181 [ 73 ], Aureocyclicin 4185 [ 80 ], Hyicin/Agneticin 4244 [ 82 ], Nukacin L217 [ 84 ], and Simulancin 3299 [ 93 ]). Moreover, several staphylococcins such as Aureocin 215FN [ 75 , 76 ], Staphylococcin 414 [ 77 ], Staphylococcin 462 [ 78 ], and BacCH91 [ 79 ] have also been detected in cow nares, turkey, mink, and poultry, respectively.…”

Biological Dark Matter Exploration using Data Mining for the Discovery of Antimicrobial Natural Products

“…In Staphylococcus aureus 4181, a strain involved in bovine mastitis, a bacteriocin-denominated aureocin 4181, is involved in resistance against multidrug-resistant (MDR) staphylococci. Interestingly, both BAGEL4 and antiSMASH v.5.0 were implemented in the identification of the gene cluster coding for aureocin 4181 45 , 46 . The findings were confirmed in the wet lab.…”