Nisin H Is a New Nisin Variant Produced by the Gut-Derived Strain Streptococcus hyointestinalis DPC6484

Abstract

dAccumulating evidence suggests that bacteriocin production represents a probiotic trait for intestinal strains to promote dominance, fight infection, and even signal the immune system. In this respect, in a previous study, we isolated from the porcine intestine a strain of Streptococcus hyointestinalis DPC6484 that displays antimicrobial activity against a wide range of Grampositive bacteria and produces a bacteriocin with a mass of 3,453 Da. Interestingly, the strain was also found to be immune to a nisin-producing strain. Genome sequencing revealed the genetic determinants responsible for a novel version of nisin, designated nisin H, consisting of the nshABTCPRKGEF genes, with transposases encoded between nshP and nshR and between nshK and nshG. A similar gene cluster is also found in S. hyointestinalis LMG14581. Notably, the cluster lacks an equivalent of the nisin immunity gene, nisI. Nisin H is proposed to have the same structure as the prototypical nisin A but differs at 5 amino acid positions-Ile1Phe (i.e., at position 1, nisin A has Ile while nisin H has Phe), Leu6Met, Gly18Dhb (threonine dehydrated to dehydrobutyrine), Met21Tyr, and His31Lys--and appears to represent an intermediate between the lactococcal nisin A and the streptococcal nisin U variant of nisin. Purified nisin H inhibits a wide range of Gram-positive bacteria, including staphylococci, streptococci, Listeria spp., bacilli, and enterococci. It represents the first example of a natural nisin variant produced by an intestinal isolate of streptococcal origin.

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

“…Differences in nisin cluster gene arrangements have been described before [12,19,51] and have been proposed to be a consequence of horizontal gene transfer, but up to now only nisin H has been found to be different in its gene content, with the absence of a detectable nisI [12]. At the prepeptide level, the nsoA genes deviated from the conserved leader peptide and cleavage sequences found in other nisA genes.…”

“…However, it was interesting to note that the native producer B. obeum showed sensitivity to nisin A, suggesting that the immunity system may require induction. O'Connor et al [12] also found that the native nisin U-producing strain S. uberis was inhibited by supernatant from a nisin A producer.…”

“…The nisin A biosynthetic cluster is located within a 70 kb transposon named Tn5307, which has been shown to be transferrable by conjugation [11]. To date, eight natural forms of nisin have been identified from either lactococci (A, Z, F and Q) or streptococci (U, U2, P and H), with nisin H representing the first example from a gastrointestinal tract bacterium [12]. A related nisin homologue has also been identified in the thermophilic bacterium Geobacillus thermodenitrificans [13].…”

“…NisFEG and NisI control self-immunity, while the two-component sensor histidine kinase system NisRK allows self-induction of the nisA promoter by the mature nisin product [7]. The modified nisin A and U molecules have been shown to have the capacity to act as inducers of their own and each other's promoters, even when attached to their leader peptides [19], while cross-immunity has also been demonstrated between nisins A and Z [20] and A and H [12].…”

Isolation and Thermal Stabilization of Bacteriocin Nisin Derived from Whey for Antimicrobial Modifications of Polymers

“…The bacteriocins are designated nisin A, nisin Z, nisin Q, F nisin (Lactococcus lactis), and nisin U (Streptococcus uberis) [2][3][4][5][6]. Recently, nisin H variant produced by Streptococcus hyointestinalis was described by O'Connor et al [7].…”