| Peer-reviewed | Experimental study | Bacteria, animals, people |
A form of bacteria that lives harmlessly on cats has been used to successfully treat drug-resistant skin infections in mice, according to a report published today in eLife.
This image, taken with an electron microscope, shows the cell wall thickening and the membrane folding back on itself in an S. pseudintermedius bacterium exposed to antimicrobials from a species of S. felis. Image credit: O’Neill et al.
(CC BY 4.0)
These protective bacteria produce antimicrobial substances that can kill off emerging pathogens and could be used as bacteriotherapies against severe animal and human skin infections.
Skin is colonised by hundreds of diverse bacterial species that play important roles in skin health, immunity and fighting infection. These commensal microbes vary extensively between animals and humans, but all species need to maintain a diverse balance of healthy skin bacteria to crowd out potential pathogens. With antiseptic or antibiotic treatment, this community becomes disrupted and drug-resistant pathogens can thrive. An alternative treatment approach is to restore the community of microbes that promote healthy skin.
“The transplantation of commensal antimicrobial bacteria as a therapeutic against infections from drug-resistant bacteria has shown some clinical promise,” explains first author Alan O’Neill, Assistant Project Scientist at the Department of Dermatology, University of California San Diego School of Medicine, US. “We and others have identified commensal species on healthy human skin that have antimicrobial activity against pathogens, but very little is known regarding the antimicrobial activity of bacteria from animal commensal groups. We set out to identify whether staphylococci collected from dogs and cats have antibacterial activity against a drug-resistant bacteria that causes severe skin infections.”
The team focused on finding bacteria with activity against methicillin-resistant Staphylococcus pseudintermedius (MRSP), an important emerging pathogen that can jump between species and causes severe atopic dermatitis.
They began by collecting 58 staphylococcus isolates from cats and dogs and growing them on agar plates alongside MRSP. From this, they found five strains that inhibited the pathogen’s growth by 80%. Two of the strains were feline or canine-derived MRSP, and three were a different species from cats – called Staphylococcus felis (S. felis). The most potent of the S. felis strains was taken forwards for further investigation.
The team first looked for the antimicrobial substances produced by S. felis that were active against MRSP. By analysing the liquid that S. felis had been cultured in, they quickly identified some small protein fragments with anti-MRSP activity called PSMs, but these alone did not account for all the antibacterial activity. They then searched the genome of S. felis to find further clues, and found genes that code for a well-known antibacterial metabolite called a micrococcin. Together these accounted for the antimicrobial activity, and further analysis showed that these substances kill MRSP by disrupting its cell wall and increasing the production of toxic free radicals.
Having established how S. felis kills bacteria, the next step was to see whether it could work as a therapy against Staphylococcus pseudintermedius (S. pseudintermedius) colonisation and infection in mice. The team exposed mice to the most common form of the pathogen and then added either S. felis bacteria or bacterial extract to the same site. Remarkably, the skin showed a reduction in scaling and redness after the treatment with both forms of S. felis compared with animals that had no treatment. There were also fewer viable S. pseudintermedius bacteria left on the skin after treatment with S. felis. When they tested the bacteriotherapy’s effectiveness for treating deep tissue infection over 14 days, the mice treated with S. felis extract had slower infection progression from day one to two and significantly better protection from day four onwards.
“We have shown that a commensal species from cats has broad-spectrum antimicrobial and anti-inflammatory activity, making it an attractive biotherapeutic candidate for the treatment of skin disease,” concludes senior author Richard Gallo, Distinguished Professor and Founding Chair of Dermatology at the Department of Dermatology, University of California San Diego School of Medicine. “Our findings indicate that a commensal bacterium from another species could be used as a bacteriotherapy as an alternative to antibiotics for hard-to-treat infections.”
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