Recent research shows the potential of bacteriophages in controlling Salmonella spp. In poultry and pig farming. Their use at different stages of the production cycle can also help to reduce the use of antibiotics and mitigate the phenomenon of antimicrobial resistance (AMR), which is now widespread in many livestock farms. (1)
Bacteriophages
Bacteriophages (or phages) are obligate parasitic viruses that live exclusively at the expense of bacteria, resulting in their death in most cases. The two possible replication cycles influence the bacterial cell killing capacity:
1) Lithic cycle. The phage adheres to the bacterial cell surface and injects DNA into it, inducing new phage synthesis and death by lysis (i.e., cell dissolution) of the host bacterium,
2) lysogenic cycle. The phage DNA integrates with that of the bacterium and is replicated with it. In some cases there may be a transition to the lytic cycle, but generally it leads to the bacterium acquiring phage resistance and establishing a mutualistic relationship. (2)
Lytic phages are preferred, in therapeutic applications, because they can directly attack and kill bacterial cells without possible side effects. They are even capable of destroying multidrug-resistant (MDR) strains, benefiting humans and animals, and can be used to promote increased food safety by reducing the microbial load on food. (3)
Benefits in animal husbandry
The first discovery of the benefits of phages on farms dates back to the beginning of the last century, thanks to Félix d’Herelle, who observed their ability to reduce chicken mortality from typhus. In recent decades, an albeit limited number of studies have since shown with appropriate trials on poultry and pigs how bacteriophages are able to reduce microbial load on the farm and on carcasses. (4)
The combination of phages and antibiotics in turn appears worthy of further investigation, to increase the killing of pathogenic bacteria and decrease the AMR phenomenon, thanks in part to the enhanced lytic action of the phages themselves. (5) Following initial studies conducted in vitro, field trials are awaited to validate this synergistic action.
Commercial beans and applications
Several phage products are already commercially available and can be used to treat Salmonella in the pre- and post-slaughter stages in the case of farm animals. Some products have already received approval from regulatory agencies such as FDA(Food & Drug Administration, USA), others are patented but not yet recognized by authorities. (6)
One of them has been shown to significantly reduce the concentration of Salmonella on chicken breasts under room temperature conditions in a modified atmosphere, as well as on fresh meat in general and ready-to-eat products. Other products have also been found to reduce populations of
Listeria monocytogenes
and Escherichia coli O157:H7 in both meat and plant products, further increasing the safety of processed food products. (7)
Current challenges
The high potential of the phages suggests further research and development, with a view to their widespread application in the fight against Salmonella. The main challenges to be faced today include:
– bean selection. The most virulent phages for bacterial strains, capable of implementing a lytic cycle that ensures their elimination rather than increasing their resistance, must be identified,
– phage distribution so that they can reach the site of bacterial colonization and operate effectively. Formulations should protect phages until bactericidal action is carried out, taking into account species differences, even in acidic environments such as the intestine,
– phage-resistance. The overuse of bacteriophages may induce a manifestation of resistance on the part of the bacteria and make the use of this alternative strategy ineffective as well, as seen with antibiotics,
– regulation. Phages can be used as additives in feed, medicines, as well as for disinfection of processing environments. In regulatory contexts other than the EU (where ex-post disinfection is strictly prohibited), even for carcass and meat processing. (8)
Interim conclusions
The use of bacteriophages appears promising for countering Salmonella and improving food safety through targeted actions on farms. This strategy is still relatively young and requires further work. Artificial intelligence tools can reduce screening time, facilitate phage-bacteria matching, and decrease the development of resistance phenomena. (9)
In the near future, phages could be integrated with other tools (e.g., microbiota stimulation) to concretely implement the One Health approach. That is to say, fostering the state of good health in a balanced condition in the human-animal-environment system, as noted. In the face of the need to drastically reduce the use of antibiotics (in animal husbandry as in medicine), to counteract the development of AMR and MDR(multi-drug resistant) strains.
Andrea Adelmo Della Penna and Dario Dongo
Notes
(1) Thanki et al. (2021). Potential Roles for Bacteriophages in Reducing Salmonella from Poultry and Swine. In book: Salmonella – a Challenge From Farm to Fork. Intechopen, doi:10.5772/intechopen.96984
(2) Fillol-Salom et al. (2019). Bacteriophages benefit from generalized transduction. PLoS Pathog. 15(7):e1007888, https://doi.org/10.1371/journal.ppat.1007888
(3) Lin et al. (2017). Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J. Gastrointest. Pharmacol. Ther. 8(3):162–173, https://dx.doi.org/10.4292/wjgpt.v8.i3.162
(4) Loponte et al. (2021). Phage Therapy in Veterinary Medicine. Antibiotics 10:421, https://doi.org/10.3390/antibiotics10040421
(5) Jeon et al. (2021). Evaluation of phage adsorption to Salmonella Typhimurium exposed to different levels of pH and antibiotic. Microbial Pathogenesis 150:104726, https://doi.org/10.1016/j.micpath.2020.104726
(6) Jamal et al. (2019). Bacteriophages: an overview of the control strategies against multiple bacterial infections in different fields. Journal of Basic Microbiology 59(2):123-133, https://doi.org/10.1002/jobm.201800412
(7) Sukurman et al. (2016). Reduction of Salmonella on chicken breast fillets stored under aerobic or modified atmosphere packaging by the application of lytic bacteriophage preparation SalmoFreshTM. Poultry Science 95:668-675, http://dx.doi.org/10.3382/ps/pev332
(8) Polaska et al. (2019). Bacteriophages-a new hope or a huge problem in the food industry. AIMS Microbiol. 5(4):324–346, https://dx.doi.org/10.3934/microbiol.2019.4.324
(9) Nami et al. (2021). Application of machine learning in bacteriophage research. BMC Microbiology 21:193, https://doi.org/10.1186/s12866-021-02256-5
Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
