Bio-Engineered Nisin with Increased Anti-Staphylococcus and Selectively Reduced Anti-Lactococcus Activity for Treatment of Bovine Mastitis

Abstract

Bovine mastitis is a significant economic burden for dairy enterprises, responsible for premature culling, prophylactic and therapeutic antibiotic use, reduced milk production and the withholding (and thus wastage) of milk. There is a desire to identify novel antimicrobials that are expressly directed to veterinary applications, do not require a lengthy milk withholding period and that will not have a negative impact on the growth of lactic acid bacteria involved in downstream dairy fermentations. Nisin is the prototypical lantibiotic, a family of highly modified antimicrobial peptides that exhibit potent antimicrobial activity against many Gram-positive microbes, including human and animal pathogens including species of Staphylococcus and Streptococcus. Although not yet utilized in the area of human medicine, nisin is currently applied as the active agent in products designed to prevent bovine mastitis. Over the last decade, we have harnessed bioengineering strategies to boost the specific activity and target spectrum of nisin against several problematic microorganisms. Here, we screen a large bank of engineered nisin derivatives to identify novel derivatives that exhibit improved specific activity against a selection of staphylococci, including mastitis-associated strains, but have unchanged or reduced activity against dairy lactococci. Three such peptides were identified; nisin A M17Q, nisin A T2L and nisin A HTK.

Biopolymer‐based antimicrobial coatings for aquatic food products: A review

“…Chemical structures of nisin A, EPL, and different essential oil compounds (Burt, 2004; Field et al, 2021; Hinchliffe et al, 2021)…”

“…The mechanism of action of AMPs starts with the strong electrostatic membrane interactions between the positively charged moieties of the peptide and negatively charged constituents on the outer surface of the bacterial cell (Moravej et al, 2018). This kind of electrostatic membrane interaction results in a strong bond formation between the positively and negatively charged molecules, which F I G U R E 1 Chemical structures of nisin A, EPL, and different essential oil compounds (Burt, 2004;Field et al, 2021;Hinchliffe et al, 2021) F I G U R E 2 Schematic diagram of the antimicrobial mechanism of peptides (adapted from [Kumar et al, 2018;Liu, Sameen et al, 2021a]) leads to the transport of the antimicrobial peptides through the bacterial cell. In gram-negative bacteria, antimicrobial peptides demonstrate an uptake mechanism that is self-regulated.…”

“…Nisin is an antimicrobial peptide (bacteriocin) belonging to Class I bacteriocin, known as lantibiotics (Field et al, 2021; Santos et al, 2018) (Figure 1). Lantibiotics are characterized as small peptides having unusual amino acids such as β‐methyl‐lanthionine, lanthionine, and several dehydrated amino acids (Małaczewska & Kaczorek‐Łukowska, 2021).…”

Probiotics and Postbiotics as Substitutes of Antibiotics in Farm Animals: A Review

“…It has been shown to reduce the growth inhibition of commensal bacteria naturally occurring in milk, such as lactobacilli and lactococci. This is the next step in the development of substitutes for antibiotic therapies on farms [ 101 ].…”

Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens

“…Several studies have shown that nisin and nisin variants have efficacy against clinical pathogens, including multi-drug resistant organisms [ 31 , 32 , 33 ]. Notably, variants nisin T (K22T) and nisin PV, were reported to have increased activity against clinical S. agalactiae isolates [ 29 , 31 ], while other derivatives, such as nisin HTK, nisin M17Q and nisin T2L have demonstrated increased potency against Staphylococcus aureus strains [ 34 ]. Some nisin variants have both anti-biofilm and antimicrobial activity against clinical isolates of Staphylococcus pseudintermedius and Streptococcus uberis [ 32 , 33 , 34 , 35 ].…”