Suicin 3908, a New Lantibiotic Produced by a Strain of Streptococcus suis Serotype 2 Isolated from a Healthy Carrier Pig

Abstract

While Streptococcus suis serotype 2 is known to cause severe infections in pigs, it can also be isolated from the tonsils of healthy animals that do not develop infections. We hypothesized that S. suis strains in healthy carrier pigs may have the ability to produce bacteriocins, which may contribute to preventing infections by pathogenic S. suis strains. Two of ten S. suis serotype 2 strains isolated from healthy carrier pigs exhibited antibacterial activity against pathogenic S. suis isolates. The bacteriocin produced by S. suis 3908 was purified to homogeneity using a three-step procedure: ammonium sulfate precipitation, cationic exchange HPLC, and reversed-phase HPLC. The bacteriocin, called suicin 3908, had a low molecular mass; was resistant to heat, pH, and protease treatments; and possessed membrane permeabilization activity. Additive effects were obtained when suicin 3908 was used in combination with penicillin G or amoxicillin. The amino acid sequence of suicin 3908 suggested that it is lantibiotic-related and made it possible to identify a bacteriocin locus in the genome of S. suis D12. The putative gene cluster involved in suicin production by S. suis 3908 was amplified by PCR, and the sequence analysis revealed the presence of nine open reading frames (ORFs), including the structural gene and those required for the modification of amino acids, export, regulation, and immunity. Suicin 3908, which is encoded by the suiA gene, exhibited approximately 50% identity with bovicin HJ50 (Streptococcus bovis), thermophilin 1277 (Streptococcus thermophilus), and macedovicin (Streptococcus macedonicus). Given that S. suis 3908 cannot cause infections in animal models, that it is susceptible to conventional antibiotics, and that it produces a bacteriocin with antibacterial activity against all pathogenic S. suis strains tested, it could potentially be used to prevent infections and to reduce antibiotic use by the swine industry.

Chromosomal Conjugative and Mobilizable Elements in Streptococcus suis: Major Actors in the Spreading of Antimicrobial Resistance and Bacteriocin Synthesis Genes

“…Observations made during conjugation experiments with strain NSUI086 prompted us to search for the presence of bacteriocin synthesis clusters in our set of 214 genomes of S. suis. Three suicin synthesis clusters have been described in S. suis: suicin 65, 90-1330, and 3908 synthesis clusters [28][29][30]. These clusters have already been described in the ST25 and ST28 strains analyzed in this study [31].…”

Distribution of Suicin Gene Clusters in Streptococcus suis Serotype 2 Belonging to Sequence Types 25 and 28

“…The production of suicin 90-1330 involves a gene cluster comprising eleven genes [9]. Suicin 3908 (SuiA) is a type B (N-terminal linear and C-terminal globular moieties) lantibiotic produced by a nonvirulent (newborn germ-free pig infection model) isolate of S. suis (strain 3908; unknown ST) isolated from a healthy carrier pig, and shows some identity with bovicin HJ50 ( Streptococcus bovis ; 49.2% identity) [10]. The suicin 3908 gene cluster contains nine genes [10].…”

“…Suicin 3908 (SuiA) is a type B (N-terminal linear and C-terminal globular moieties) lantibiotic produced by a nonvirulent (newborn germ-free pig infection model) isolate of S. suis (strain 3908; unknown ST) isolated from a healthy carrier pig, and shows some identity with bovicin HJ50 ( Streptococcus bovis ; 49.2% identity) [10]. The suicin 3908 gene cluster contains nine genes [10]. Lastly, a second type B lantibiotic (suicin 65; SssA) showing a high identity with lantibiotics produced by Streptococcus pyogenes (streptococcin FF22, 84.6% identity) and L. lactis subsp.…”

Initial steps of the pathogenesis of the infection caused byStreptococcus suis: fighting against nonspecific defenses

“…Typically, lantibiotic gene clusters include a structural gene encoding a prelantibiotic peptide, as well as genes required for the modification of amino acids, export, regulation and immunity . Recently, three different lantibiotics, named suicins, produced by strains of S. suis serotype 2 were reported. The mature peptides corresponding to each suicin showed poor identity (≤24%) between each other, suggesting that they are unrelated.…”

“…Suicin 90‐1330 (SslA) is a type A (linear) lantibiotic secreted by a nonvirulent (in both mouse and pig infection models) S. suis ST28 strain . Suicin 3908 (SuiA) is a type B (N‐terminal linear and C‐terminal globular moieties) lantibiotic also produced by a nonvirulent (newborn germfree pig model) S. suis strain of unknown ST, isolated from a healthy carrier pig . Lastly, a second type B lantibiotic (suicin 65; SssA) was identified and characterized in a nonvirulent (newborn germfree pig model) S. suis ST28 strain isolated from a healthy carrier pig .…”