Novel Antimicrobial Peptide from Temporin L in The Treatment of Staphylococcus pseudintermedius and Malassezia pachydermatis in Polymicrobial Inter-Kingdom Infection

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.

Synergistic Effect of Abietic Acid with Oxacillin against Methicillin-Resistant Staphylococcus pseudintermedius

“…S = susceptible; R = resistant. The phenotypic analysis of methicillin resistance was confirmed investigating by PCR the presence or absence of mecA, mec1, mecR1 genes, as previously reported [19]. The results demonstrated that only one veterinary and two human strains possessed the mec operon (named MRSP1, MRSP2 and MRSP3, respectively), while the second veterinary strain did not (methicillin-susceptible Staphylococcus pseudintermedius (MSSP)) (data not shown).…”

Coupling Interrupted Fischer and Multicomponent Joullié‐Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

“…Antimicrobial susceptibility testing Minimal inhibitory concentrations (MIC) of all the compounds were determined in Mueller‐Hinton medium (MH) by the broth microdilution assay, following the procedure already described [55] . The compounds were added to bacterial suspension in each well yielding a final cell concentration of 1×10 6 CFU/mL and a final compound concentration ranging from 3.1 to 100 μM.…”

Synergism of a Novel 1,2,4-oxadiazole-containing Derivative with Oxacillin against Methicillin-Resistant Staphylococcus aureus

“…Here we investigated the effect of the compound 12 treatment on mecA, mec1, mecR1 gene expression modulation [19]. The treatment with the subinhibitory concentrations of 12 (1 µM and 0.39 µM), for 30 min, induced a reduced expression of all the mec operon genes, whereas oxacillin strongly induced them both at subinhibitory (0.03 µg/mL) and MIC values (10 µg/mL) (Figure 4).…”