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Researchers at the University of California San Diego School of Medicine used bacteria found in healthy cats to successfully treat a skin infection in mice. These bacteria can serve as the basis for new therapeutic agents against severe skin infections in humans, dogs and cats.
The study, which was published in eLife on October 19, 2021, was led by Richard L. Gallo, MD, PhD, Distinguished Professor and Chair of the Department of Dermatology at the UC San Diego School of Medicine, whose team focused on the use of Bacteria and their products specialize in treating disease – an approach known as “bacteriotherapy”.
The skin is colonized by hundreds of types of bacteria that play important roles in skin health, immunity, and fighting infections. All species must maintain a diverse balance of healthy skin bacteria to fight potential pathogens.
“Our health absolutely depends on these ‘good’ bacteria,” said Gallo. “They depend on our healthy skin to live, and in return some of them protect us from ‘bad’ bacteria. But when we get sick, “bad” bacteria can take advantage of our weakened immune system and cause infections. “
To identify candidates for a new bacteriotherapy against skin infections, the researchers first examined various bacteria from dogs and cats and cultivated them together with S. pseudintermedius in liquid and antimicrobial agar assays.
This is the case with methicillin-resistant Staphylococcus pseudintermedius (MRSP), a bacterium that is common in domesticated animals and becomes infectious when the animals are sick or injured. MRSP is a emerging pathogen that can switch species and cause severe atopic dermatitis or eczema. These infections are common in dogs and cats and can also occur in humans, although infection rates in humans vary around the world. As the name suggests, MRSP is resistant to common antibiotics and has been difficult to treat in clinical and veterinary settings.
To remedy this, the researchers first examined a library of bacteria that normally live on dogs and cats and grown them in the presence of MRSP. From this they identified a strain of cat bacteria called Staphylococcus felis (S. felis), which was particularly good at inhibiting MRSP growth. They found that this particular strain of S. felis naturally produces several antibiotics that kill MRSP by destroying its cell wall and increasing the production of toxic free radicals.
“The potency of this species is extreme,” said Gallo. “It is very capable of killing pathogens, partly because it attacks them from many directions – a strategy known as ‘polypharmacy’. That makes it particularly attractive as a therapeutic agent. “
Bacteria can easily develop resistance to a single antibiotic. To circumvent this, S. felis has four genes that code for four different antimicrobial peptides. Each of these antibiotics are able to kill MRSP on their own, but by working together they make it difficult for the bacteria to fight back.
After determining how S. felis kills the MRSP, the next step was to see if it could work as therapy in a live animal. The team exposed mice to the most common form of the pathogen and then added either S. felis bacteria or bacterial extract in the same spot. The skin showed a reduction in flaking and redness after each treatment compared to animals that received no treatment. Less viable MRSP bacteria were also left on the skin after treatment with S. felis.
The next steps include plans for a clinical trial to confirm whether S. felis can be used to treat MRSP infections in dogs. Bacterial therapies like this can be administered via topical sprays, creams, or gels that contain either live bacteria or purified extracts of the antimicrobial peptides.
While these products are in development, what should pet owners do in the meantime?
“Don’t stop washing your pets to keep these ‘good’ bacteria on them,” Gallo said. “The skin was designed to protect the ‘good’ bacteria, so soap and detergents usually don’t wash the good guys off.”
“It is even possible that living with a healthy cat offers people some protection from MRSP,” said Gallo, “so this could be an argument in favor of keeping pets.”
This study is part of a growing line of work by Gallo’s group to develop bacteriotherapies for inflammatory skin diseases and skin cancer.
Co-authors are: Alan M. O’Neill, Kate A. Worthing, Nikhil Kulkarni, Fengwu Li, Teruaki Nakatsuji, Dominic McGrosso, Robert H. Mills, Gayathri Kalla, Joyce Y. Cheng, Kit Pogliano, Joe Pogliano and David J. Gonzalez, all at UC San Diego, and Jacqueline M. Norris at the University of Sydney.
Funding came in part from the National Institutes of Health (grants U01AI52038, R01AI53185, R01AR076082, and R37AI052453).
Disclosure: Richard L. Gallo is a co-founder, scientific advisor, inventor, consultant and has an interest in MatriSys Biosciences and is an advisor, receives income and has an interest in Sente. Kate A. Worthing is a co-inventor of the technology described in this study, which was submitted to the University of California San Diego.
