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 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.
Similar content being viewed by others
References
Acedo JZ, Chiorean S, Vederas JC, van Belkum MJ (2018) The expanding structural variety among bacteriocins from Gram-positive bacteria. FEMS Microbiol Rev 42:805–828
Cotter PD, Ross RP, Hill C (2013) Bacteriocins—a viable alternative to antibiotics? Nat Rev Microbiol 11:95–105
Newstead LL, Varjonen K, Nuttall T, Paterson GK (2020) Staphylococcal-produced bacteriocins and antimicrobial peptides: their potential as alternative treatments for Staphylococcus aureus infections. Antibiotics 9:40
Coelho MLV, Duarte AFS, Bastos MCF (2017) Bacterial labionin-containing peptides and sactibiotics: unusual types of antimicrobial peptides with potential use in clinical settings (a review). Curr Top Med Chem 17:1177–1198
Diep DB, Skaugen M, Salehian Z, Holo H, Nes IF (2007) Common mechanisms of target cell recognition and immunity for class II bacteriocins. Proc Natl Acad Sci U S A 104:2384–2389
Giambiagi-de Marval M, Mafra MA, Penido EGC, Bastos MCF (1990) Distinct groups of plasmids correlated with bacteriocin production in Staphylococcus aureus. J Gen Microbiol 136:1591–1599
Netz DJA, Sahl H-G, Marcolino R, Nascimento JS, Oliveira SS, Soares MB, Bastos MCF (2001) Molecular characterisation of aureocin A70, a multi-peptide bacteriocin isolated from Staphylococcus aureus. J Mol Biol 311:939–949
Fagundes PC, Farias FM, Santos OCS, Paz JAS, Ceotto-Vigoder H, Alviano DS, Romanos MTV, Bastos MCF (2016) The four-component aureocin A70 as a promising agent for food biopreservation. Int J Food Microbiol 237:39–46
Gamon MR, Moreira EC, Oliveira SS, Teixeira LM, Bastos MCF (1999) Characterization of a novel bacteriocin-encoding plasmid found in clinical isolates of Staphylococcus aureus. Antonie van Leeuwenhoek 75:233–243
Nascimento JS, Santos KRN, Gentilini E, Sordelli D, Bastos MCF (2002) Phenotypic and genetic characterization of bacteriocin-producing strains of Staphylococcus aureus involved in bovine mastitis. Vet Microbiol 85:133–144
Nascimento JS, Fagundes PC, Brito MAVP, Bastos MCF (2005) Production of bacteriocins by coagulase-negative staphylococci involved in bovine mastitis. Vet Microbiol 106:61–71
Brito MAVP, Somkuti GA, Renye JA (2011) Production of antilisterial bacteriocins by staphylococci isolated from bovine milk. J Dairy Sci 94:1194–1200
Ceotto H, Nascimento JS, Brito MAVP, Bastos MCF (2009) Bacteriocin production by Staphylococcus aureus involved in bovine mastitis in Brazil. Res Microbiol 160:592–599
Bastos MCF, Ceotto H, Coelho MLV, Nascimento JS (2009) Staphylococcal antimicrobial peptides: relevant properties and potential biotechnological applications. Curr Pharm Biotechnol 10:38–61
Coelho MLV, Nascimento JS, Fagundes PC, Madureira DJ, Oliveira SS, Brito MAVP, Bastos MCF (2007) Activity of staphylococcal bacteriocins against Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis. Res Microbiol 158:625–630
Farias FM, Nascimento JS, Santos OCS, Bastos MCF (2019) Study of effectiveness of staphylococcins in biopreservation of Minas fresh (Frescal) cheese with a reduced sodium content. Int J Food Microbiol 304:19–31
Ceotto H, Brede DA, Salehian Z, Nascimento JS, Fagundes PC, Nes IF, Bastos MCF (2010) Aureocins 4185, bacteriocins produced by Staphylococcus aureus 4185: potential application in food preservation. Foodborne Pathog Dis 7:1255–1262
Nascimento JS, Coelho MLV, Ceotto H, Potter A, Fleming LR, Salehian Z, Nes IF, Bastos MCF (2012) Genes involved in immunity to and secretion of aureocin A53, an atypical class II bacteriocin produced by Staphylococcus aureus A53. J Bacteriol 194:875–883
Duarte AFS, Ceotto-Vigoder H, Barrias EM, Souto-Padrón TCBS, Nes IF, Bastos MCF (2018) Hyicin 4244, the first sactibiotic described in staphylococci, exhibits an anti-staphylococcal biofilm activity. Int J Antimicrob Agents 51:349–356
Brede DA, Faye T, Johnsborg O, Odegard I, Nes IF, Holo H (2004) Molecular and genetic characterization of propionicin F, a bacteriocin from Propionibacterium freudenreichii. Appl Environ Microbiol 70:7303–7310
Peters EC, Horn DM, Tully DC, Brock A (2001) A novel multifunctional labeling reagent for enhanced protein characterization with mass spectrometry. Rapid Commun Mass Spectrom 15:2387–2392
Silva NCC, Guimarães FF, Manzi MP, Budri PE, Gómez-Sanz E, Benito D, Langoni H, Rall VLM, Torres C (2013) Molecular characterization and clonal diversity of methicillin-susceptible Staphylococcus aureus in milk of cows with mastitis in Brazil. J Dairy Sci 96:6856–6862
Ceotto H, Dias RCS, Nascimento JS, Brito MAVP, Giambiagi-deMarval M, Bastos MCF (2012) Aureocin A70 production is disseminated amongst genetically unrelated Staphylococcus aureus involved in bovine mastitis. Lett Appl Microbiol 54:455–461
Jack RW, Tagg JR, Ray B (1995) Bacteriocins of Gram-positive bacteria. Microbiol Rev 59:171–200
Ruegg PL (2017) A 100-year review: mastitis detection, management, and prevention. J Dairy Sci 100:10381–10397
Gomes F, Henriques M (2015) Control of bovine mastitis: old and recent therapeutic approaches. Curr Microbiol 72:377–382
Nascimento JS, Abrantes J, Giambiagi-deMarval M, Bastos MCF (2004) Growth conditions required for bacteriocin production by strains of Staphylococcus aureus. World J Microbiol Biotechnol 20:941–947
Coelho MLV, Ceotto H, Madureira DJ, Nes I, Bastos MCF (2009) Mobilization functions of the bacteriocinogenic plasmid pRJ6 of Staphylococcus aureus. J Microbiol 47:327–336
Coelho MLV, Fleming LR, Bastos MCF (2016) Insights into aureocin A70 regulation: participation of regulator AurR, alternative transcription factor σB and phage ϕ11 regulator cI. Res Microbiol 167:90–102
Coelho MLV, Coutinho BG, Santos OCS, Nes IF, Bastos MCF (2014) Immunity to the Staphylococcus aureus leaderless four-peptide bacteriocin aureocin A70 is conferred by AurI, an integral membrane protein. Res Microbiol 165:50–59
Ovchinnikov KV, Chi H, Mehmeti I, Holo H, Nes IF, Diep DB (2016) Novel group of leaderless multipeptide bacteriocins from Gram-positive bacteria. Appl Environ Microbiol 82:5216–5224
de Vos WM, Mulders JWM, Siezen RJ, Hugenholtz J, Kuipers OP (1993) Properties of nisin Z and distribution of its gene, nisZ, in Lactococcus lactis. Appl Environ Microbiol 59:213–218
Hanchi H, Hammami R, Fernandez B, Kourda R, Ben Hamida J, Fliss I (2016) Simultaneous production of formylated and nonformylated enterocins L50A and L50B as well as 61A, a new glycosylated durancin, by Enterococcus durans 61A, a strain isolated from artisanal fermented milk in Tunisia. J Agric Food Chem 64:3584–3590
Netz DJA, Pohl R, Beck-Sinckinger AG, Selmer T, Pierik AJ, Bastos MCF, Sahl H-G (2002) Biochemical characterization and genetic analysis of aureocin A53, a new, atypical bacteriocin from Staphylococcus aureus. J Mol Biol 319:745–756
Wladyka B, Piejko M, Bzowska M, Pieta P, Krzysik M, Mazurek L, Guevara-Lora I, Bukowski M, Sabat AJ, Friedrich AW, Bonar E, Miedzobrodzki J, Dubin A, Ma P (2015) A peptide factor secreted by Staphylococcus pseudintermedius exhibits properties of both bacteriocins and virulence factors. Sci Rep 5:14569
Ryan MP, Flynn J, Hill C, Ross RP, Meaney WJ (1999) The natural food grade inhibitor, lacticin 3147, reduced the incidence of mastitis after experimental challenge with Streptococcus dysgalactiae in nonlactating dairy cows. J Dairy Sci 82:2208–2114
Acknowledgments
SLSMB and GSA were recipients of scholarships from CAPES/Brazil (Finance Code 001) and PIBIC/UFRJ, respectively. PCF is recipient of a fellowship from FAPERJ/Brazil. Genome sequencing was performed at the University of the State of Rio de Janeiro (UERJ), Brazil.
Funding
This work was supported by a research program funded by the National Council for Scientific and Technological Development (CNPq, 303.602/2015-5), Brazil, to MCFB.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declared that they have no conflict of interest.
Additional information
Responsible Editor: Gisele Monteiro
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOC 1672 kb)
Rights and permissions
About this article
Cite this article
Salustiano Marques-Bastos, S.L., Varella Coelho, M.L., Ceotto-Vigoder, H. et al. Molecular characterization of aureocin 4181: a natural N-formylated aureocin A70 variant with a broad spectrum of activity. Braz J Microbiol 51, 1527–1538 (2020). https://doi.org/10.1007/s42770-020-00315-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42770-020-00315-z