Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane

Natamycin is a polyene antibiotic that is commonly used as an antifungal agent because of its broad spectrum of activity and the lack of development of resistance. Other polyene antibiotics, like nystatin and filipin are known to interact with sterols, with some specificity for ergosterol thereby causing leakage of essential components and cell death. The mode of action of natamycin is unknown and is investigated in this study using different in vitro and in vivo approaches. Isothermal titration calorimetry and direct binding studies revealed that natamycin binds specifically to ergosterol present in model membranes. Yeast sterol biosynthetic mutants revealed the importance of the double bonds in the B-ring of ergosterol for the natamycin-ergosterol interaction and the consecutive block of fungal growth. Surprisingly, in strong contrast to nystatin and filipin, natamycin did not change the permeability of the yeast plasma membrane under conditions that growth was blocked. Also, in ergosterol containing model membranes, natamycin did not cause a change in bilayer permeability. This demonstrates that natamycin acts via a novel mode of action and blocks fungal growth by binding specifically to ergostero

Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane

Natamycin is a polyene antibiotic that is commonly used as an antifungal agent because of its broad spectrum of activity and the lack of development of resistance. Other polyene antibiotics, like nystatin and filipin are known to interact with sterols, with some specificity for ergosterol thereby causing leakage of essential components and cell death. The mode of action of natamycin is unknown and is investigated in this study using different in vitro and in vivo approaches. Isothermal titration calorimetry and direct binding studies revealed that natamycin binds specifically to ergosterol present in model membranes. Yeast sterol biosynthetic mutants revealed the importance of the double bonds in the B-ring of ergosterol for the natamycin-ergosterol interaction and the consecutive block of fungal growth. Surprisingly, in strong contrast to nystatin and filipin, natamycin did not change the permeability of the yeast plasma membrane under conditions that growth was blocked. Also, in ergosterol containing model membranes, natamycin did not cause a change in bilayer permeability. This demonstrates that natamycin acts via a novel mode of action and blocks fungal growth by binding specifically to ergostero

Lesões de pele em bovinos com doença granulomatosa sistêmica associada ao pastoreio de ervilhaca (Vicia spp.) Skin lesions in cattle with systemic granulomatous disease associated to pasturing vetch (Vicia spp.)

Descrevem-se as lesões cutâneas macroscópicas em 10 e histológicas em 8 vacas afetadas por doença granulomatosa sistêmica associada ao pastoreio de ervilhaca (Vicia spp.). Em todos os casos, as lesões cutâneas eram caracterizadas por múltiplas áreas coalescentes de alopecia, liquenificação e descamação. Os locais mais atingidos pela lesão de pele foram: cabeça e pescoço (10/10), tronco (4/10), períneo (3/10) e mama (2/10). Em todos os 8 casos avaliados histologicamente, as lesões se caracterizavam por dermatite perivascular superficial granulomatosa de intensidade variável. Outros achados histológicos incluíram dermatite perivascular profunda (1/8), perifoliculite (2/8), foliculite mural (3/8), hiperqueratose ortoqueratótica compacta (6/8), erosões (1/8), úlceras (2/8), microabscessos de Munro (8/8), crostas serocelulares (1/8), espongiose (4/8), degeneração hidrópica (5/8), acantólise (1/8), corpúsculos de Civatte (2/8), exocitose linfoplasmocitária (6/8), edema superficial (6/8), incontinência pigmentar (2/8), basofilia (6/8) e mineralização distrófica do colágeno (2/8), tumefação do núcleo das células endoteliais (8/8) e ectasia de glândulas sudoríparas (8/8).<br>Gross and histopathological lesions in the skin of respectively 10 and 8 cows affected with systemic granulomatous disease associated with pasturing vetch (Vicia spp.) are described. In all cases, the cutaneous lesions were characterized by multiple coalescent areas of alopecia, lichenification and desquamation. More frequently affected sites were the skin covering the head and neck (10/10), trunk (4/10), escutcheon (3/10) and mammary gland (2/10). In all 8 histologically examined cases the lesions were characterized by superficial perivascular granulomatous dermatitis of varying intensity. Other histological findings included deep perivascular dermatitis (1/8), perifoliculitis (2/8), mural foliculitis (3/8), compact orthokeratotic hyperkeratosis (6/8), erosions (1/8), ulcers (2/8), Munro’s microabscess (8/8), serocellular crusts (1/8), spongiosis (4/8), hydropic degeneration (5/8), acantholysis (1/8), Civatte bodies (2/8), lymphoplasmacytic exocytosis (6/8), superficial edema (6/8), pigmentary incontinence (2/8), basophilia (6/8) and collagen dystrophic mineralization (2/8), swollen nucleus of endothelial cells (8/8) and sweat gland ectasy (8/8)