Breaking down the walls of the SRS bacterium
Chilean scientists have discovered compounds capable of inhibiting the growth of Piscirickettsia salmonis, opening new perspectives for health control in salmon farming.
Published
Unlike traditional antibiotics, which act on specific metabolic processes, some antimicrobial peptides directly destroy the bacterial membrane. In this context, Chilean scientists discovered two peptides, tachyplecin I and protegrin-1, that have a significant capacity to inhibit the growth of Piscirickettsia salmonis, the bacterium that causes salmonid rickettsial septicaemia (SRS).
SRS is a significant fish health problem for the Chilean salmon farming industry, and is becoming more of a problem in Ireland, Scotland, and Norway, albeit in a less virulent form.
In conversation with Fish Farming Expert’s Chilean sister site, Salmonexpert.cl, Dr Jorge Beltrán, a researcher at the University of La Frontera and one of the experts involved in this discovery, analyses the findings in depth, addressing the mechanisms of action of the peptides, their real scope, and the steps that are still needed to take this innovation from the laboratory to the fish farms.
In their study, researchers identified beta-hairpin peptides as leading candidates. What structural characteristics explain their greater efficacy against P. salmonis?
The evidence supports a mechanism primarily associated with the bacterial envelope ... Unlike many conventional antibiotics, these peptides do not necessarily rely on blocking a single intracellular protein.
The two most active candidates, tachyplecin I and protegrin-1, are short peptides with an approximate positive charge of +7 and a beta-hairpin structure stabilised by two disulphide bridges. This architecture keeps them relatively pre-organised and reduces the structural reorganisation required to interact with the bacterial membrane. The combination of positively charged and hydrophobic residues favours both recognition of the bacterial envelope and interaction with its lipids.
The simulations showed distinct behaviours: tachyplecin I remained more compact and primarily positioned its central region close to the membrane, while protegrin-1 adopted a more extended arrangement, anchoring itself by its ends and establishing more contacts and hydrogen bonds with the lipids. However, tachyplecin I was more potent in the experimental assay. This indicates that efficacy depends not only on the number of contacts the peptide forms, but also on how well it maintains its structure and on subsequent membrane perturbation processes.
What is the main mechanism of action of these peptides on the bacteria?
The evidence supports a mechanism primarily associated with the bacterial envelope. The most likely model comprises several stages: initial attraction of the cationic peptide to the bacterial surface, adsorption, interfacial insertion, and subsequent alteration of membrane permeability and integrity. Unlike many conventional antibiotics, these peptides do not necessarily rely on blocking a single intracellular protein.
From a practical perspective, how far are we from seeing these types of solutions applied in fish farms?
We are still in an early preclinical stage of discovery and prioritisation. The study allowed us to select the candidates that justify further experimental investment, but it does not yet constitute the development of a product applicable in aquaculture facilities.
Before reaching that stage, it will be necessary to confirm activity against different strains, evaluate toxicity and selectivity in salmonid cells, haemolysis, stability in serum and biological media, activity against the bacteria within infected cells, formulation, route of administration, pharmacokinetics, and efficacy in fish. Subsequently, controlled challenge trials, production studies, and regulatory evaluation would be required. Therefore, it is premature to establish a specific timeframe.
Do you envision these peptides as a therapeutic treatment, a preventative treatment, or both?
We envision both possibilities, although current evidence relates more directly to therapeutic use, because we have demonstrated inhibition of bacterial growth once the microorganism is exposed to the peptide. Its use as an adjunct to other interventions could also be explored, although such combinations still need to be tested.
What are the next steps in the study?
The next steps should be carried out in stages: expanding the analysis to LF-89-like, EM-90-like strains and field isolates; confirming activity through viable counts and death kinetics assays; and determining stability, cytotoxicity, haemolysis, and selectivity in salmonid cells. Because P. salmonis is a facultative intracellular pathogen, it will be especially important to verify that the peptides can control infection within fish cells.
Next, it will be necessary to optimise the formulation and route of administration, study distribution and persistence in tissues, and conduct safety and controlled challenge trials in fish. Only after obtaining favourable results would it be reasonable to proceed to pilot tests under production conditions.
Based on these results, we are developing a line of synthetic peptides with rationally designed and controlled properties, supported by in-house developed machine learning and deep learning algorithms. Our goal is to simultaneously optimise antimicrobial activity, stability, selectivity against fish cells, and the feasibility of large-scale production.
