Date Published: April 30, 2019
Publisher: Public Library of Science
Author(s): Yukun Sun, Iva A. Veseli, Katy Vaillancourt, Michel Frenette, Daniel Grenier, Jean-François Pombert, Axel Cloeckaert.
The Gram-positive α-hemolytic Streptococcus suis is a major pathogen in the swine industry and an emerging zoonotic agent that can cause several systemic issues in both pigs and humans. A total of 35 S. suis serotypes (SS) have been identified and genotyped into > 700 sequence types (ST) by multilocus sequence typing (MLST). Eurasian ST1 isolates are the most virulent of all S. suis SS2 strains while North American ST25 and ST28 strains display moderate to low/no virulence phenotypes, respectively. Notably, S. suis 90–1330 is an avirulent Canadian SS2-ST28 isolate producing a lantibiotic bacteriocin with potential prophylactic applications. To investigate the suitability of this strain for such purposes, we sequenced its complete genome using the Illumina and PacBio platforms. The S. suis 90–1330 bacteriocin was found encoded in a locus cargoed in what appears to be an integrative and conjugative element (ICE). This bacteriocin locus was also found to be widely distributed across several streptococcal species and in a few Staphylococcus aureus strains. Because the locus also confers protection from the bacteriocin, the potential prophylactic benefits of using this strain may prove limited due to the spread of the resistance to its effects. Furthermore, the S. suis 90–1330 genome was found to code for genes involved in blood survival, suggesting that strain may not be a benign as previously thought.
The quick rise of antibiotics resistance in the microbial world is problematic to multiple fields, including the food industry. As such, novel antibiotic compounds and alternate strategies to treat infections and prevent growth of pathogenic bacterial species are increasingly being sought after. One promising avenue is the prophylactic use of bacteriocin-producing commensal or neutral species as probiotics to outcompete virulent ones . Bacteriocins form a wide range of antimicrobial peptides produced by microorganisms . These molecules, frequently short peptides, can affect a narrow to large spectrum of bacteria excluding the species producing the compounds, which are immune to their effects via varying mechanisms . Because of the potentially disruptive effects on the microflora of the host, the ideal species for prophylactic use would produce compounds whose spectrum do not disrupt the commensal organisms inhabiting the targeted environment. Recently, a nisin-related lantibiotic bacteriocin with a membrane permeabilization activity has been found in Streptococcus suis strain 90–1330 . This lanthionine-containing bacteriocin is a killing peptide active against a number of Gram-positive streptococcal and staphylococcal species but shows little to no activity against Gram-negative bacteria .
In healthy microbiotas, the presence of commensal and/or neutral microorganisms outcompete pathogenic species for the limited pool of nutrients, resources available and adherence sites, providing a helpful barrier against diseases. This helpful association between host and commensal/neutral microorganisms forms the basis behind the prophylactic use of probiotics. Intuitively, prospective probiotics should be devoid of toxicity and side effects while providing clear positive benefits to the health of the individual(s). Recently, strain 90–1330 from the low virulence/nonvirulent Streptococcus suis serotype 2 –sequence type 28 was shown to express a bacteriocin with a membrane permeabilization effect that inhibits not only the growth of virulent serotype 2 strains of S. suis, but also of other Gram positive swine pathogens–including species hyicus and aureus from the genus Staphylococcus . This suggested that its use as a probiotic could serve as a robust preventive method in the swine industry. Here we determined the complete sequence of the S. suis 90–1330 genome to investigate its suitability as a probiotic. However, our results suggest that the use of this strain for prophylactic purposes may not yield the expected benefits and that despite is apparent lack of virulence [4,18], S. suis 90–1330 may not be entirely harmless.
The intent for this study was to look for the suitability of using S. suis 90–1330 as a prophylactic strain in the swine industry. However, based on our results, we cannot recommend its use as is without further engineering given the apparent mobility of its lantibiotic bacteriocin locus cargoed in what is likely an integrative and conjugative element. But even if this element is no longer mobile, given the wide distribution of this bacteriocin and its resistance mechanism across several streptococcal species, the use of this S. suis isolate as a probiotic may provide only limited protection against virulent strains. Furthermore, based on its genetic paraphernalia, the S. suis 90–1330 strain may not be as benign as previously thought and further testing and/or engineering would be required to ensure the safety of the animals subjected to potential prophylactic treatments involving this strain. Considering all the above, administering the bacteriocin directly as food preservative/supplement using alternate mechanisms that are not reliant on probiotics may prove a better approach to minimize undesirable outcomes, and further work will be required to determine if using this bacteriocin in such a fashion would indeed be effective.