Abstract
Interkingdom polymicrobial diseases are caused by different microorganisms that colonize the same niche, as in the case of yeast-bacteria coinfections. The latter are difficult to treat due the absence of any common therapeutic target for their elimination, both in animals and humans. Staphylococcus pseudintermedius and Malassezia pachydermatis belong to distinct kingdoms. They can colonize the same skin district or apparatus being the causative agents of fastidious pet animals’ pathologies. Here we analysed the antimicrobial properties of a panel of 11 peptides, derived from temporin L, against Malassezia pachydermatis. Only peptide 8 showed the best mycocidal activity at 6.25 μM. Prolonged application of peptide 8 did not cause M. pachydermatis drug-resistance. Peptide 8 was also able to inhibit the growth of Staphylococcus pseudintermedius, regardless of methicillin resistance, at 1.56 μM for methicillin-susceptible S. pseudintermedius (MSSP) and 6.25 μM for methicillin-resistant S. pseudintermedius (MRSP). Of interest, peptide 8 increased the susceptibility of MRSP to oxacillin. Oxacillin MIC value reduction was of about eight times when used in combination with peptide 8. Finally, the compound affected the vitality of bacteria embedded in S. pseudintermedius biofilm. In conclusion, peptide 8 might represent a valid therapeutic alternative in the treatment of interkingdom polymicrobial infections, also in the presence of methicillin-resistant bacteria.
Highlights
Polymicrobial inter-kingdom infections represent a serious problem in clinical practice [1].The copresence of bacteria and fungi at the site of infection can decrease antimicrobial efficacy and the administration of a combined mixture of antimicrobials is necessary
Peptide 1 was considered as a lead for a subsequent structure-activity relationship (SAR) study, focused on the Gly10, which was replaced by diverse amino acids with the aim to improve the antimicrobial activity [13]. Starting from these promising outcomes, we explored the antimicrobial activity of a compound library, recently realized by our group, on M. pachydermatis [13]
Our results showed that peptide 8 inhibited the growth of both S. pseudintermedius strains (MSSP and methicillin-resistant S. pseudintermedius (MRSP))
Summary
Polymicrobial inter-kingdom infections represent a serious problem in clinical practice [1].The copresence of bacteria and fungi at the site of infection can decrease antimicrobial efficacy and the administration of a combined mixture of antimicrobials is necessary. Malassezia pachydermatis is part of the normal microbiota of the skin and ear canal of dogs and cats where it causes dermatitis. It is Antibiotics 2020, 9, 530; doi:10.3390/antibiotics9090530 www.mdpi.com/journal/antibiotics. Antibiotics 2020, 9, 530 the most common microorganism isolated from canine otitis externa [2]. The latter is a non-lethal chronic disease that troubles both dogs and owners for a long period. M. pachydermatis can be isolated from healthy and diseased human skin, and it is the causative agent of nosocomial infections in neonates suggesting the transmission from pet animals [3,4,5]. Due to the recurrence of yeast infections, routine antifungal administration in pets may induce acquired resistance, leading to treatment failure
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