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Mycopathologia Apr 2023Malassezia pachydermatis is part of the normal skin microbiota of various animal species but under certain circumstances becomes an opportunistic pathogen producing...
Malassezia pachydermatis is part of the normal skin microbiota of various animal species but under certain circumstances becomes an opportunistic pathogen producing otitis and dermatitis. Commonly these Malassezia diseases are effectively treated using azoles. However, some cases of treatment failure have been reported. Alterations in the ERG11 gene have been associated with in vitro azole resistance in M. pachydermatis. In the present study, in vitro antifungal susceptibility of 89 different strains of M. pachydermatis isolated from different animal species and health status was studied. The susceptibility to fluconazole (FLZ), itraconazole (ITZ), ketoconazole and amphotericin B was tested by a disk diffusion method and 17 strains were also subjected to an ITZ E-test. Mueller-Hinton supplemented with 2% glucose and methylene blue was used as culture medium in both susceptibility assays. Multilocus sequence typing was performed in 30 selected strains using D1D2, ITS, CHS2 and β-tubulin genes. Also, ERG11 gene was sequenced. The four antifungals tested were highly effective against most of the strains. Only two strains showed no inhibition zone to antifungals and a strain showed an increased MIC to ITZ. The study of the ERG11 sequences revealed a high diversity of DNA sequences and a total of 23 amino acid substitutions, from which only two have been previously described. Also, three deleterious substitutions (A302T, G459D and G461D) previously associated with azole resistance in this yeast were recovered. A correlation between certain genotypes and ERG11 mutations was observed. Some of the ERG11 mutations recovered were correlated with a reduced susceptibility to azoles.
Topics: Animals; Antifungal Agents; Azoles; Malassezia; Ketoconazole; Itraconazole; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 36495417
DOI: 10.1007/s11046-022-00696-9 -
Journal of Fungi (Basel, Switzerland) Jun 2020is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated... (Review)
Review
is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated with multiple antifungal agents, mainly azole derivatives. This manuscript aims to review the available evidence regarding the occurrence of resistance phenomena in this organism. Various findings support the capacity of for developing resistance. These include some reports of treatment failure in dogs, the reduced antifungal activity found against yeast isolates sampled from dogs with exposure to antifungal drugs and strains exposed to antifungal agents in vitro, and the description of resistance mechanisms. At the same time, the data reviewed may suggest that the development of resistance is a rare eventuality in canine practice. For example, only three publications describe confirmed cases of treatment failure due to antifungal resistance, and most claims of resistance made by past studies are based on interpretive breakpoints that lack sound support from the clinical perspective. However, it is possible that resistant cases are underreported in literature, perhaps due to the difficulty of obtaining a laboratory confirmation given that a standard procedure for susceptibility testing of is still unavailable. These considerations highlight the need for maintaining surveillance for the possible emergence of clinically relevant resistance, hopefully through a shared strategy put in place by the scientific community.
PubMed: 32630397
DOI: 10.3390/jof6020093 -
Journal of Fungi (Basel, Switzerland) Nov 2022The yeast , an opportunistic pathogen that inhabits the skin of various domestic and wild animals, is capable of producing a biofilm that plays an important role in...
The yeast , an opportunistic pathogen that inhabits the skin of various domestic and wild animals, is capable of producing a biofilm that plays an important role in antifungal resistance. The aim of this research study was to find the intensity of biofilm production by strains isolated from the ear canal of healthy dogs, and to determine the susceptibility of planktonic, adhered and biofilm-forming cells to three azole antifungals-itraco-nazole, voriconazole and posaconazole-that are most commonly used to treat infections. Out of 52 isolates, 43 strains (82.7%) were biofilm producers with varying levels of intensity. For planktonic cells, the minimum inhibitory concentration (MIC) range was 0.125-2 µg/mL for itraconazole, 0.03-1 µg/mL for voriconazole and 0.03-0.25 µg/mL for posaconazole. Only two isolates (4.7%) were resistant to itraconazole, one strain (2.3%) to voriconazole and none to posaconazole. For adhered cells and the mature biofilm, the following MIC ranges were found: 0.25-16 µg/mL and 4-16 µg/mL for itraconazole, 0.125-8 µg/mL and 0.25-26 µg/mL for voriconazole, and 0.03-4 µg/mL and 0.25-16 µg/mL for posaconazole, respectively. The least resistance for adhered cells was observed for posaconazole (55.8%), followed by voriconazole (62.8%) and itraconazole (88.4%). The mature biofilm of showed 100% resistance to itraconazole, 95.3% to posaconazole and 83.7% to voriconazole. The results of this study show that higher concentrations of commonly used antifungal agents are needed to control infections caused by biofilm-forming strains of .
PubMed: 36422031
DOI: 10.3390/jof8111209 -
The Journal of Veterinary Medical... Mar 2023Canine Malassezia dermatitis and otitis externa are generally treated by antifungal drugs. However, multi-drug-resistant strains of Malassezia pachydermatis have been...
Canine Malassezia dermatitis and otitis externa are generally treated by antifungal drugs. However, multi-drug-resistant strains of Malassezia pachydermatis have been reported worldwide. Given the presence of these multi-drug-resistant strains, it is unclear which antifungal agent is the most effective for canine Malassezia dermatitis and canine otitis. In this study, we attempted to determine the most effective drug against azole-resistant M. pachydermatis. Susceptibility to azoles and terbinafine (TBF) was assessed using a modified broth microdilution method. In all tested isolates, the minimum inhibitory concentration at 90% of organisms (MIC) were 16 to >32 μg/mL for the azoles, and 2 μg/mL for TBF. All of the strains that showed low susceptibility to both itraconazole and miconazole were also relatively susceptible to TBF.
Topics: Animals; Dogs; Azoles; Terbinafine; Malassezia; Japan; Antifungal Agents; Microbial Sensitivity Tests; Dermatitis; Dog Diseases
PubMed: 36724970
DOI: 10.1292/jvms.22-0358 -
ACS Infectious Diseases Sep 2022Fungal promoted infections are becoming a severe health global emergency due to drug-resistant phenomena and zoonosis. This work investigated compounds bearing...
Fungal promoted infections are becoming a severe health global emergency due to drug-resistant phenomena and zoonosis. This work investigated compounds bearing acyl-/selenoureido moieties and primary/secondary sulfonamide groups as novel antifungal agents acting through organism-directed selenium toxicity and inhibition of the newly emergent therapeutic target, the Carbonic Anhydrases (CAs; EC 4.2.1.1). Reported data clearly indicate that seleno-containing scaffolds with respect to the standard-of-care drugs showed appreciable antifungal activity, which was suppressed when the chalcogen was replaced with its cognate isosteric elements sulfur and oxygen. In addition, such compounds showed excellent selectivity against over its related genus strains and . Safe cytotoxicity profiles on bovine kidney cells (MDBK) and human HaCat cells, as well as the shallow hemolytic activity on defibrinated sheep blood, allowed us to consider these compounds as up-and-coming novel antifungals.
Topics: Animals; Antifungal Agents; Carbonic Anhydrases; Cattle; Humans; Mycoses; Sheep; Sulfonamides
PubMed: 35984421
DOI: 10.1021/acsinfecdis.2c00250 -
Frontiers in Cellular and Infection... 2020and are lipophilic and lipid dependent yeasts, associated with the skin microbiota in humans and domestic animals, respectively. Although they are commensals, under...
and are lipophilic and lipid dependent yeasts, associated with the skin microbiota in humans and domestic animals, respectively. Although they are commensals, under specific conditions they become pathogens, causing skin conditions, such as pityriasis versicolor, dandruff/seborrheic dermatitis, folliculitis in humans, and dermatitis and otitis in dogs. Additionally, these species are associated with fungemia in immunocompromised patients and low-weight neonates in intensive care units with intravenous catheters or with parenteral nutrition and that are under-treatment of broad-spectrum antibiotics. The host-pathogen interaction mechanism in these yeasts is still unclear; for this reason, it is necessary to implement suitable new host systems, such as . This infection model has been widely used to assess virulence, host-pathogen interaction, and antimicrobial activity in bacteria and fungi. Some advantages of the model are: (1) the immune response has phagocytic cells and antimicrobial peptides that are similar to those in the innate immune response of human beings; (2) no ethical implications; (3) low cost; and (4) easy to handle and inoculate. This study aims to establish as an infection model for and . To achieve this objective, first, larvae were first inoculated with different inoculum concentrations of these two species, 1.5 × 10 CFU/mL, 1.5 × 10 CFU/mL, 1.5 × 10 CFU/mL, and 11.5 × 10 CFU/mL, and incubated at 33 and 37°C. Then, for 15 days, the mortality and melanization were evaluated daily. Finally, the characterization of hemocytes and fungal burden assessment were as carried out. It was found that at 33 and 37°C both and successfully established a systemic infection in . proved to be slightly more virulent than at a temperature of 37°C. The results suggest that larvae mortality and melanization is dependent on the specie of , the inoculum concentration and the temperature. According to the findings, can be used as an model of infection to conduct easy and reliable approaches to boost our knowledge of the genus.
Topics: Animals; Dandruff; Dogs; Host-Pathogen Interactions; Humans; Malassezia; Skin
PubMed: 32432057
DOI: 10.3389/fcimb.2020.00199 -
Medical Mycology Journal 2022Azole resistance in Malassezia pachydermatis has been reported in isolates from canine skin worldwide. Decreased susceptibility of M. pachydermatis to azoles has been...
Azole resistance in Malassezia pachydermatis has been reported in isolates from canine skin worldwide. Decreased susceptibility of M. pachydermatis to azoles has been hypothesized to potentially result from mutations in the ERG11 gene, which encodes lanosterol 14α-demethylase. To sequence the mutation hotspots of ERG11 in the isolates, we prepared primers (MPERG11hot2S and MPERG11hot2R) based on the conserved sequences of M. pachydermatis ERG11. DNA samples from azole-resistant and -susceptible strains were amplified by PCR using the primer pair. PCR amplicons were sequenced and analyzed for single-nucleotide polymorphisms (SNPs) in the target gene. Seven of the tested azole-resistant strains (16 strains) harbored ERG11 SNPs at nucleotide 904 (G→A) or 905 (C→T), resulting in the replacement of Ala 302 with Thr or Val (Ala302Thr or Val). None of the tested azole-susceptible strains had a mutation at either of those residues. Our PCR method detected SNPs at the nucleotide-905 (C→T) hotspot mutation site in M. pachydermatis ERG11. Moreover, we discovered an additional hot spot site at nucleotide 904 (G→A).
Topics: Animals; Dogs; Antifungal Agents; Azoles; Drug Resistance, Fungal; Malassezia; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide
PubMed: 35650071
DOI: 10.3314/mmj.21-00013 -
Open Veterinary Journal 2022External otitis is common in dogs, and one of the main agents involved is , a yeast belonging to the otic microbiota. Empirical treatment can fail; therefore, it is...
BACKGROUND
External otitis is common in dogs, and one of the main agents involved is , a yeast belonging to the otic microbiota. Empirical treatment can fail; therefore, it is essential to know the antifungal susceptibility profile to prescribe appropriate treatment, a fact scarcely reported in Chile.
AIM
This study aimed to determine the antifungal sensitivity of isolated from the external auditory canal of dogs in central Chile.
METHODS
Ear swabs from 30 dogs (15 healthy and 15 with external otitis) were used. Samples were subjected to cytology and fungal culture. The antifungal susceptibility was determined according to clinical and laboratory standards institute (CLSI) document M44A-2 using the disk diffusion test from amphotericin B, Caspofungin, fluconazole, nystatin, clotrimazole, and voriconazole were used.
RESULTS
The prevalence of was 66.7% from 8 healthy dogs and 12 with otitis. While fungal culture was not associated with the patient's clinical condition ( = 0.24), the yeast count by cytology was significantly higher in dogs with otitis ( = 0.003). The strains were sensitive to all antifungals except for Caspofungin, where 55% of the strains were resistant.
CONCLUSION
is isolated more frequently in dogs with otitis, and the ear cytological examination is useful to differentiate colonized dogs versus dogs with otitis. In addition, most antifungals are active against this yeast, except Caspofungin, an antifungal used in human medicine. This situation should be further monitored in epidemiological programs to evaluate the possible impact on Chilean public health.
Topics: Animals; Antifungal Agents; Caspofungin; Chile; Dermatomycoses; Dog Diseases; Dogs; Malassezia; Otitis Externa; Saccharomyces cerevisiae
PubMed: 35342729
DOI: 10.5455/OVJ.2022.v12.i1.12 -
Journal of Enzyme Inhibition and... Dec 2022Warm-blooded animals may have on healthy skin, but changes in the skin microenvironment or host defences induce this opportunistic commensal to become pathogenic....
Warm-blooded animals may have on healthy skin, but changes in the skin microenvironment or host defences induce this opportunistic commensal to become pathogenic. Malassezia infections in humans and animals are commonly treated with azole antifungals. Fungistatic treatments, together with their long-term use, contribute to the selection and the establishment of drug-resistant fungi. To counteract this rising problem, researchers must find new antifungal drugs and enhance drug resistance management strategies. Cyclic adenosine monophosphate, adenylyl cyclase, and bicarbonate have been found to promote fungal virulence, adhesion, hydrolase synthesis, and host cell death. The CO/HCO/pH-sensing in fungi is triggered by HCO produced by metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1). It has been demonstrated that the growth of can be inhibited by primary sulphonamides, which are the typical CA inhibitors. Here, we report the cloning, purification, and characterisation of the -CA (MpaCA) from the pathogenic fungus , which is homologous to the enzyme encoded in the genome of and , that are responsible for dandruff and seborrhoeic dermatitis. Fungal CAs could be thus considered a new pharmacological target for combating fungal infections and drug resistance developed by most fungi to the already used drugs.
Topics: Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Dose-Response Relationship, Drug; Malassezia; Molecular Structure; Recombinant Proteins; Structure-Activity Relationship
PubMed: 34894958
DOI: 10.1080/14756366.2021.1994559 -
Veterinary Medicine and Science Mar 2022The antifungal efficacy of cold atmospheric microwave plasma (CAMP) against Malassezia pachydermatis has not been to be evaluated.
BACKGROUND
The antifungal efficacy of cold atmospheric microwave plasma (CAMP) against Malassezia pachydermatis has not been to be evaluated.
OBJECTIVE
To examine the antifungal effects of CAMP against M. pachydermatis and its synergistic effects with chlorhexidine gluconate (CHX).
METHODS
A M. pachydermatis isolate was collected from a dog with otitis externa and Malassezia dermatitis at the Seoul National University Veterinary Medical Teaching Hospital. The antifungal effect was determined by applying CAMP to a M. pachydermatis isolate that was incubated for 3 days at 37°C. After 1, 2, 3 and 5 min of application, the efficacy of the plasma treatment was determined according to the number of colony forming units (CFUs). A mixture consisting of inoculum and CHX was applied to evaluate the synergistic effect of the plasma treatment in the same way.
RESULTS
The application of CAMP showed significant antifungal effects against M. pachydermatis. The antifungal effect of CAMP was enhanced by an increased exposure time and output power. The application of CAMP with 0.02% and 0.2% CHX resulted in lower survival rates against M. pachydermatis when compared with its sole application at 1 or 2 min.
CONCLUSIONS
The study findings demonstrate that CAMP has a potential as a new antifungal option for M. pachydermatis and has synergistic antifungal effects with CHX in vitro. Clinical applications for CAMP are necessary to assess the antifungal efficacy for patients.
Topics: Animals; Antifungal Agents; Chlorhexidine; Dog Diseases; Dogs; Humans; Malassezia; Microwaves; Plasma Gases
PubMed: 35089639
DOI: 10.1002/vms3.719