In Vitro Activity of 3 Commercial Bacteriophage Cocktails Against Salmonella and Shigella spp. Isolates of Human Origin

Main Article Content

Odette J. Bernasconi
Valentina Donà
Regula Tinguely
Andrea Endimiani


Background: Salmonella and Shigella spp. are 2 of the most frequent and deadly enteric bacterial pathogens recorded worldwide. In developing countries Salmonella infections are responsible for many deaths annually and these mortality rates are prone to increase due to the emergence of resistance to antibiotics. In this overall scenario new alternative therapeutic approaches are needed.

Methods: For the first time, we investigated the activity of 3 commercial bacteriophage cocktails (INTESTI, Septaphage, PYO) against a collection of contemporary Salmonella spp. (n = 30) and Shigella spp. (n = 20) strains isolated in Switzerland. Phage susceptibility was determined by implementing the spot test.

Results: The overall susceptibility of Salmonella spp. to INTESTI and Septaphage was 87% and 77%, respectively. With regard to Shigella spp., the overall susceptibility to INTESTI and Septaphage was 95% and 55%, respectively. PYOwas observed to be active against only 10% of Salmonella spp. but against 95% of Shigella spp.

Conclusions: Our results seem promising, especially for the INTESTI biopreparation against Salmonella enterica infections. Nevertheless, such speculation should be supported by further in vivo studies to confirm efficacy and safety of the cocktails. We also emphasize the importance of large in vitro screening analyses aimed to assess the activity of such biopreparations against contemporary multidrug-resistant strains that are emerging worldwide.

Keywords: commercial; bacteriophages; Salmonella; Shigella cocktails


Download data is not yet available.

Article Details

Author Biography

Andrea Endimiani, Institute for Infectious Diseases, University of Bern, Bern, Switzerland

Institute for Infectious Diseases

Principal Investigator and Medical Microbiologist


1. Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson MA, Roy SL, Jones JL, Griffin PM. Foodborne illness acquired in the United States--major pathogens. Emerg Infect Dis. 2011;17(1):7-15. PubMed PMID: 21192848. Pubmed Central PMCID: 3375761. doi: 10.3201/eid1701.P11101

2. Gu B, Cao Y, Pan S, Zhuang L, Yu R, Peng Z, Qian H, Wei Y, Zhao L, Liu G, Tong M. Comparison of the prevalence and changing resistance to nalidixic acid and ciprofloxacin of Shigella between Europe-America and Asia-Africa from 1998 to 2009. Int J Antimicrob Agents. 2012;40(1):9-17. PubMed PMID: 22483324. doi: 10.1016/j.ijantimicag.2012.02.005

3. Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, Adak GK, Levine MM. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ. 1999;77(8):651-66. PubMed PMID: 10516787. Pubmed Central PMCID: 2557719

4. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013;382(9888):209-22. PubMed PMID: 23680352. doi: 10.1016/S0140-6736(13)60844-2

5. Threlfall EJ. Antimicrobial drug resistance in Salmonella: problems and perspectives in food- and water-borne infections. FEMS Microbiol Rev. 2002;26(2):141-8. PubMed PMID: 12069879.

6. Su LH, Chiu CH, Chu C, Ou JT. Antimicrobial resistance in nontyphoid Salmonella serotypes: a global challenge. Clin Infect Dis. 2004;39(4):546-51. PubMed PMID: 15356819. doi: 10.1086/422726

7. Domingo-Calap P, Georgel P, Bahram S. Back to the future: bacteriophages as promising therapeutic tools. HLA. 2016;87(3):133-40. PubMed PMID: 26891965. doi: 10.1111/tan.12742

8. Vandenheuvel D, Lavigne R, Brussow H. Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials. Annu Rev Virol. 2015;2(1):599-618. PubMed PMID: 26958930. doi: 10.1146/annurev-virology-100114-054915

9. Bao H, Zhang P, Zhang H, Zhou Y, Zhang L, Wang R. Bio-Control of Salmonella Enteritidis in Foods Using Bacteriophages. Viruses. 2015;7(8):4836-53. PubMed PMID: 26305252. Pubmed Central PMCID: 4576208. doi: 10.3390/v7082847

10. Ahmadi M, Karimi Torshizi MA, Rahimi S, Dennehy JJ. Prophylactic Bacteriophage Administration More Effective than Post-infection Administration in Reducing Salmonella enterica serovar Enteritidis Shedding in Quail. Front Microbiol. 2016;7:1253. PubMed PMID: 27555842. Pubmed Central PMCID: 4977285. doi: 10.3389/fmicb.2016.01253

11. Mohammed M, Cormican M. Whole genome sequencing provides possible explanations for the difference in phage susceptibility among two Salmonella Typhimurium phage types (DT8 and DT30) associated with a single foodborne outbreak. BMC Res Notes. 2015;8:728. PubMed PMID: 26613761. Pubmed Central PMCID: 4661946. doi: 10.1186/s13104-015-1687-6

12. Karpe YA, Kanade GD, Pingale KD, Arankalle VA, Banerjee K. Genomic characterization of Salmonella bacteriophages isolated from India. Virus Genes. 2016;52(1):117-26. PubMed PMID: 26757942. doi: 10.1007/s11262-015-1269-7

13. Borie C, Albala I, Sanchez P, Sanchez ML, Ramirez S, Navarro C, Morales MA, Retamales AJ, Robeson J. Bacteriophage treatment reduces Salmonella colonization of infected chickens. Avian Dis. 2008;52(1):64-7. PubMed PMID: 18459298. doi: 10.1637/8091-082007-Reg

14. Mai V, Ukhanova M, Reinhard MK, Li M, Sulakvelidze A. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota. Bacteriophage. 2015;5(4):e1088124. PubMed PMID: 26909243. Pubmed Central PMCID: 4745833. doi: 10.1080/21597081.2015.1088124

15. Kutateladze M, Adamia R. Phage therapy experience at the Eliava Institute. Med Mal Infect. 2008;38(8):426-30. PubMed PMID: 18687542. doi: 10.1016/j.medmal.2008.06.023

16. Zschach H, Joensen KG, Lindhard B, Lund O, Goderdzishvili M, Chkonia I, Jgenti G, Kvatadze N, Alavidze Z, Kutter EM, Hasman H, Larsen MV. What Can We Learn from a Metagenomic Analysis of a Georgian Bacteriophage Cocktail? Viruses. 2015;7(12):6570-89. PubMed PMID: 26703713. Pubmed Central PMCID: 4690881. doi: 10.3390/v7122958

17. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; CLSI document M100-S26, 2016. Wayne, PA.

18. Martha R.J. Clokie, Kropiski AM. Bacteriophages. Methods and Protocols, Volume 1: Isolation, Characterization, and Interactions. Book: Methods in Molecular Biology™ 2009;501.

19. Khan Mirzaei M, Nilsson AS. Isolation of phages for phage therapy: a comparison of spot tests and efficiency of plating analyses for determination of host range and efficacy. PLoS One. 2015;10(3):e0118557. PubMed PMID: 25761060. Pubmed Central PMCID: 4356574. doi: 10.1371/journal.pone.0118557

20. Fukushima M, Kakinuma K, Kawaguchi R. Phylogenetic analysis of Salmonella, Shigella, andEscherichia coli strains on the basis of the gyrB gene sequence. J Clin Microbiol. 2002;40(8):2779-85. PubMed PMID: 12149329. Pubmed Central PMCID: 120687.

21. Samson JE, Magadan AH, Sabri M, Moineau S. Revenge of the phages: defeating bacterial defences. Nat Rev Microbiol. 2013;11(10):675-87. PubMed PMID: 23979432. doi: 10.1038/nrmicro3096

22. Bowen A, Hurd J, Hoover C, Khachadourian Y, Traphagen E, Harvey E, Libby T, Ehlers S, Ongpin M, Norton JC, Bicknese A, Kimura A, Centers for Disease C, Prevention. Importation and domestic transmission of Shigella sonnei resistant to ciprofloxacin - United States, May 2014-February 2015. MMWR Morb Mortal Wkly Rep. 2015;64(12):318-20. PubMed PMID: 25837241.

23. Seiffert SN, Perreten V, Johannes S, Droz S, Bodmer T, Endimiani A. OXA-48 carbapenemase-producing Salmonella enterica serovar Kentucky isolate of sequence type 198 in a patient transferred from Libya to Switzerland. Antimicrob Agents Chemother. 2014;58(4):2446-9. PubMed PMID: 24468781. Pubmed Central PMCID: 4023741. doi: 10.1128/AAC.02417-13

Most read articles by the same author(s)