Lipid composition and sensitivity of Prototheca wickerhamii to membrane-active antimicrobial agents

Sud, Inder Jit; Feingold, David S.

doi:10.1128/aac.16.4.486

Cited by 22 publications

(10 citation statements)

References 28 publications

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“…The proposed lytic mechanism for BMAP-28 is supported by CD spectra which indicate capacity to interact with anionic LUVs (models for bacterial membranes) and with ergosterol-containing zwitterionic liposomes (models for fungal/algal membranes). The plasma membrane of Prototheca is rich in zwitterionic phospholipids (>70% by weight of total phospholipids) and ergosterol (4% of total neutral lipid w/w) [48]. Our results are consistent with published evidence that BMAP-28 induces substantial calcein release from artificial liposomes with a composition mimicking that of fungal membranes and causes rapid uptake of the dye SYTOX green into the hyphae of the plant pathogen Fusarium oxysporum f. sp.…”

Section: Discussionsupporting

confidence: 91%

Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp.

Tomasinsig

Skerlavaj

Scarsini

et al. 2011

Journal of Peptide Science

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The yeast-like algae of the genus Prototheca are ubiquitous saprophytes causing infections in immunocompromised patients and granulomatous mastitis in cattle. Few available therapies and the rapid spread of resistant strains worldwide support the need for novel drugs against protothecosis. Host defence antimicrobial peptides inactivate a wide array of pathogens and are a rich source of leads, with the advantage of being largely unaffected by microbial resistance mechanisms. Three structurally diverse bovine peptides [BMAP-28, Bac5 and lingual antimicrobial peptide (LAP)] have thus been tested for their capacity to inactivate Prototheca spp. In minimum inhibitory concentration (MIC) assays, they were all effective in the micromolar range against clinical mastitis isolates as well as a Prototheca wickerhamii reference strain. BMAP-28 sterilized Prototheca cultures within 30-60 min at its MIC, induced cell permeabilization with near 100% release of cellular adenosine triphosphate and resulted in extensive surface blebbing and release of intracellular material as observed by scanning electron microscopy. Bac5 and LAP inactivated Prototheca following 3-6 h incubation at fourfold their MIC and did not result in detectable surface damage despite 70-90% killing, suggesting they act via non-lytic mechanisms. In circular dichroism studies, the conformation of BMAP-28, but not that of Bac5 or LAP, was affected by interaction with liposomes mimicking algal membranes. Our results indicate that BMAP-28, Bac5 and LAP kill Prototheca with distinct potencies, killing kinetics, and modes of action and may be appropriate for protothecal mastitis treatment. In addition, the ability of Bac5 and LAP to act via non-lytic mechanisms may be exploited for the development of target-selective drugs.

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Section: Discussionsupporting

confidence: 91%

Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp.

Tomasinsig

Skerlavaj

Scarsini

et al. 2011

Journal of Peptide Science

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“…There is no record of the allylamine antifungal terbinafine being used for the treatment of protothecosis in dogs. Terbinafine inhibits squalene epoxidase, preventing the synthesis of cell wall ergosterol, which has been found in Prototheca species capsules (Sud and Feingold 1979). …”

Section: Introductionmentioning

confidence: 98%

Prototheca wickerhamii in a dog with cutaneous, ocular and systemic manifestations and treatment with terbinafine

Milley

Labelle²,

Tolar³

et al. 2015

Vet Record Case Reports

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A two-year-old intact female collie presented with a tentative diagnosis of systemic blastomycosis based on compatible clinical signs and history and a positive urine Blastomyces antigen enzyme immunoassay. The dog was subsequently correctly diagnosed with protothecosis based on ocular and paw pad histopathology and in vitro culture of Prototheca wickerhamii from paw pad tissue. Histopathology revealed organisms in deep tissue samples as well as in the epidermis and superficial keratin layers of the paw pad. Serum (1→3)-β-d-glucan testing was negative. The dog was treated with terbinafine based on in vitro susceptibility results. There are no previous reports of terbinafine use for the treatment of canine protothecosis. Neurological and gastrointestinal symptoms remained stable with terbinafine. While there was an overall improvement in cutaneous lesions and attitude over the course of eight weeks on treatment, the animal did not survive despite therapy.

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“…A potential reason for the susceptibility to polyene and azole agents is the presence of ergosterol in the neutral lipid fraction of the cell membranes of Prototheca species (141). In particular, P. wickerhamii exhibits a membrane ergosterol content of 4%.…”

Section: Susceptibility Profilesmentioning

confidence: 99%

Human Protothecosis

2007

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SUMMARY Human protothecosis is a rare infection caused by members of the genus Prototheca. Prototheca species are generally considered to be achlorophyllic algae and are ubiquitous in nature. The occurrence of protothecosis can be local or disseminated and acute or chronic, with the latter being more common. Diseases have been classified as (i) cutaneous lesions, (ii) olecranon bursitis, or (iii) disseminated or systemic manifestations. Infections can occur in both immunocompetent and immunosuppressed patients, although more severe and disseminated infections tend to occur in immunocompromised individuals. Prototheca wickerhamii and Prototheca zopfii have been associated with human disease. Usually, treatment involves medical and surgical approaches; treatment failure is not uncommon. Antifungals such as ketoconazole, itraconazole, fluconazole, and amphotericin B are the most commonly used drugs to date. Among them, amphotericin B displays the best activity against Prototheca spp. Diagnosis is largely made upon detection of characteristic structures observed on histopathologic examination of tissue.

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Lipid composition and sensitivity of Prototheca wickerhamii to membrane-active antimicrobial agents

Cited by 22 publications

References 28 publications

Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp.

Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp.

Prototheca wickerhamii in a dog with cutaneous, ocular and systemic manifestations and treatment with terbinafine

Human Protothecosis

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