Combating the emergence and spread of multidrug-resistant Staphylococcus pseudintermedius in companion animals and its zoonotic transmission by phage therapy: An alternative therapeutic approach

• Grant number: 24/01488-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date until: August 01, 2024
• End date until: July 31, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ana Cristina Gales
• Grantee: Ikechukwu Benjamin Moses
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The increasing spread and transmission of antibiotic-resistant S. pseudintermedius from pets (especially dogs and cats) to humans threaten animal and human health worldwide. Most importantly, multidrug-resistant S. pseudintermedius (MDRSP), including the methicillin-resistant S. pseudintermedius (MRSP) strains have emerged as a significant public health problem in veterinary medicine and entails further consequences for humans (especially pet owners/guardians, veterinary personnel, and immunocompromised individuals) in close contacts with pets. The epidemiological situation is further exacerbated as the gene driving drug resistance (SCCmec) in MRSP is highly mobile and can be transferred between different staphylococcal species colonizing humans (such as S. aureus) and other zoonotic hosts. Since dogs are in close contact with their owners, the risk of transmission of MDRSP between dogs and humans is a serious public health problem which could draw back the gains of One-Health. The treatment of S. pseudintermedius infections has become more complicated and challenging with the emergence and increasing spread of MRSP, especially as a result of the increasing frequency of dog ownership worldwide. Besides being resistant to beta-lactam derivatives due to mecA gene which encodes for an altered penicillin binding protein (PBP2a), MRSP has been noted to be notoriously multidrug-resistant with reported resistances to tetracyclines, sulphonamides, fluoroquinolones, aminoglycosides, macrolides, and phenicols. This limits therapeutic options and could lead to uncontrollable deaths, especially if the last line antibiotics become ineffective. With the emergence, increasing spread, and zoonotic transmission of MDRSP, especially MRSP strains in veterinary and human medicine, there has been a renewed interest in phage therapy which employs bacteriophages (viruses that infect or attack bacteria) in antibiotherapies to serve as an alternative therapeutic approach in combating this emerging zoonotic pathogen. Phage therapy to tackle bacterial infections in human and animal (especially livestock) infections have been explored in some published research; however, studies on bacteriophage therapy in the treatment of S. pseudintermedius infections, especially those caused by MDRSP pathogens, including the MRSP strains, are very scarce; hence, this study. In this research project, S. pseudintermedius bacteriophages will be isolated from different sources, identified, and molecularly characterized. The in vitro and in vivo protective efficacies of the isolated bacteriophages, their stability in different environmental conditions (such as pH and temperature), and their synergistic activity with antibiotics will also be assessed.