Natamycin
Eye Infections, Fungal
Corneal Ulcer
Corneal Perforation
Fusariosis
Nystatin
Filipin
Antifungal Agents
Fusarium
Ergosterol
Ophthalmic Solutions
The biosynthetic gene cluster for the 26-membered ring polyene macrolide pimaricin. A new polyketide synthase organization encoded by two subclusters separated by functionalization genes. (1/70)
The biosynthetic gene cluster for the 26-membered ring of the polyene macrolide pimaricin extends for about 110 kilobase pairs of contiguous DNA in the genome of Streptomyces natalensis. Two sets of polyketide synthase (PKS) genes are separated by a group of small polyketide-functionalizing genes. Two of the polyketide synthase genes, pimS0 and pimS1, have been fully sequenced and disrupted proving the involvement of each of these genes in pimaricin biosynthesis. The pimS0 gene encodes a relatively small acetate-activating PKS (approximately 193 kDa) that appears to work as a loading protein which "presents" the starter unit to the second PKS subunit. The pimS1 gene encodes a giant multienzyme (approximately 710 kDa) harboring 15 activities responsible for the first four cycles of chain elongation in pimaricin biosynthesis, resulting in formation of the polyene chromophore. (+info)Natamycin in genital candidosis in men. (2/70)
In a trial of natamycin, an antifungal antibiotic in a vanishing cream base, assessment was possible in 66 men with genital or anal candidosis. The overall cure rate was 82 percent, In 43 patients with culturally proven candidosis it was 98 percent. but in 23 patients treated solely on clinical impression it was only 52 percent. Symptoms were rapidly relieved in those who responded and there were no side-effects. In our hands, natamycin 2 per cent cream has proved to be a valuable preparation in the treatment of candidal balanitis. (+info)Dematiaceous fungal keratitis. Clinical isolates and management. (3/70)
Clinical and laboratory features of 16 cases of keratitis that were caused by dematiaceous pigmented fungi are reported. Management, including the treatment of nine cases with Natamycin (Pimaricin), resulted in corneal healing in 14 cases, and therapeutic surgery in two cases. (+info)New high-molecular decomposition products of natamycin (pimaricin) with intact lactone-ring. (4/70)
Mild acid treatment of natamycin (IV) results in biologically inactive aponatamycin (VI), an amphoteric substance with some natamycin-like chemical and physical properties. Aponatamycin contains one natamycin- and one natamycinolide-moiety. More drastic acid degradation of natamycin eliminates the aminosugar under formation of the dimer (VII) of the hypothetical aglycone of natamycin, natamycinolide (V) as well as a non-ionic compound, the dimer of the 12-decarboxy-11-anhydro analogue of natamycinolide. (+info)Polyene antibiotics. VII. Carbon-13 nuclear magnetic resonance evidence for cyclic hemiketals in the polyene antibiotics amphotericin B, nystatin A1, tetrin A, tetrin B, lucensomycin, and pimaricin1,2. (5/70)
Carbon magnetic resonance establishes conclusively that six polyene macrolide antibiotics containing keto groups (the heptaene amphotericin B, the tetraene-diene nystatin A1, and the tetraenes tetrin A, tetrin B, pimaricin, and lucensomycin) exist in the hemiketal form in solution. Their spectra all contain a hemiketal carbon's absorption near 97 ppm but lack a keto carbon's absorption near 210 ppm. The non-polyenic macrolide erythromycin, on the other hand, exists in the keto form. (+info)Therapeutic surgery in failures of medical treatment for fungal keratitis. (6/70)
Medical treatment failure necessitated surgery in nine cases of fungal keratitis. Therapeutic surgery eliminated fungal infection in seven cases, and useful vision was retained in five out of six penetrating keratoplasties. In three cases Natamycin (Pimaricin) therapy rendered fungi non-viable, but two were demonstrable by histopathology. These results suggest that antifungal treatment should be applied for as long as possible before therapeutic surgery in order to improve the final visual outcome. (+info)A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis. (7/70)
BACKGROUND: Polyene macrolides are a class of large macrocyclic polyketides that interact with membrane sterols, having antibiotic activity against fungi but not bacteria. Their rings include a chromophore of 3-7 conjugated double bonds which constitute the distinct polyene structure. Pimaricin is an archetype polyene, important in the food industry as a preservative to prevent mould contamination of foods, produced by Streptomyces natalensis. We set out to clone, sequence and analyse the gene cluster responsible for the biosynthesis of this tetraene. RESULTS: A large cluster of 16 open reading frames spanning 84985 bp of the S. natalensis genome has been sequenced and found to encode 13 homologous sets of enzyme activities (modules) of a polyketide synthase (PKS) distributed within five giant multienzyme proteins (PIMS0-PIMS4). The total of 60 constituent active sites, 25 of them on a single enzyme (PIMS2), make this an exceptional multienzyme system. Eleven additional genes appear to govern modification of the polyketide-derived framework and export. Disruption of the genes encoding the PKS abolished pimaricin production. CONCLUSIONS: The overall architecture of the PKS gene cluster responsible for the biosynthesis of the 26-membered polyene macrolide pimaricin has been determined. Eleven additional tailoring genes have been cloned and analysed. The availability of the PKS cluster will facilitate the generation of designer pimaricins by combinatorial biosynthesis approaches. This work represents the extensive description of a second polyene macrolide biosynthetic gene cluster after the one for the antifungal nystatin. (+info)Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis. (8/70)
BACKGROUND: The post-polyketide synthase biosynthetic tailoring of polyene macrolides usually involves oxidations catalysed by cytochrome P450 monooxygenases (P450s). Although members from this class of enzymes are common in macrolide biosynthetic gene clusters, their specificities vary considerably toward the substrates utilised and the positions of the hydroxyl functions introduced. In addition, some of them may yield epoxide groups. Therefore, the identification of novel macrolide monooxygenases with activities toward alternative substrates, particularly epoxidases, is a fundamental aspect of the growing field of combinatorial biosynthesis. The specific alteration of these activities should constitute a further source of novel analogues. We investigated this possibility by directed inactivation of one of the P450s belonging to the biosynthetic gene cluster of an archetype polyene, pimaricin. RESULTS: A recombinant mutant of the pimaricin-producing actinomycete Streptomyces natalensis produced a novel pimaricin derivative, 4,5-deepoxypimaricin, as a major product. This biologically active product resulted from the phage-mediated targeted disruption of the gene pimD, which encodes the cytochrome P450 epoxidase that converts deepoxypimaricin into pimaricin. The 4,5-deepoxypimaricin has been identified by mass spectrometry and nuclear magnetic resonance following high-performance liquid chromatography purification. CONCLUSIONS: We have demonstrated that PimD is the epoxidase responsible for the conversion of 4,5-deepoxypimaricin to pimaricin in S. natalensis. The metabolite accumulated by the recombinant mutant, in which the epoxidase has been knocked out, constitutes the first designer polyene obtained by targeted manipulation of a polyene biosynthetic gene cluster. This novel epoxidase could prove to be valuable for the introduction of epoxy substituents into designer macrolides. (+info)Natamycin is an antifungal medication used to treat and prevent fungal infections. It is a polyene macrolide antibiotic produced by the bacterium Streptomyces natalensis. In medical contexts, it is often used as a topical treatment for eye, skin, and mucous membrane infections caused by susceptible fungi. Natamycin works by binding to ergosterol, a component of fungal cell membranes, which disrupts the membrane's structure and function, ultimately leading to fungal cell death.
In addition to its medical uses, natamycin is also used as a food preservative to prevent mold growth in certain dairy products, such as cheese, and in some countries, it is approved for use in the production of certain types of sausages and fermented meat products.
Fungal eye infections, also known as fungal keratitis or ocular fungal infections, are caused by the invasion of fungi into the eye. The most common types of fungi that cause these infections include Fusarium, Aspergillus, and Candida. These infections can affect any part of the eye, including the cornea, conjunctiva, sclera, and vitreous humor.
Fungal eye infections often present with symptoms such as redness, pain, sensitivity to light, tearing, blurred vision, and discharge. In severe cases, they can lead to corneal ulcers, perforation of the eye, and even blindness if left untreated. Risk factors for fungal eye infections include trauma to the eye, contact lens wear, immunosuppression, and pre-existing eye conditions such as dry eye or previous eye surgery.
Diagnosis of fungal eye infections typically involves a thorough eye examination, including visual acuity testing, slit lamp examination, and sometimes corneal scrapings for microbiological culture and sensitivity testing. Treatment usually involves topical antifungal medications, such as natamycin or amphotericin B, and in some cases may require oral or intravenous antifungal therapy. In severe cases, surgical intervention may be necessary to remove infected tissue or repair any damage caused by the infection.
Keratitis is a medical condition that refers to inflammation of the cornea, which is the clear, dome-shaped surface at the front of the eye. The cornea plays an essential role in focusing vision, and any damage or infection can cause significant visual impairment. Keratitis can result from various causes, including bacterial, viral, fungal, or parasitic infections, as well as trauma, allergies, or underlying medical conditions such as dry eye syndrome. Symptoms of keratitis may include redness, pain, tearing, sensitivity to light, blurred vision, and a feeling of something foreign in the eye. Treatment for keratitis depends on the underlying cause but typically includes antibiotics, antivirals, or anti-fungal medications, as well as measures to alleviate symptoms and promote healing.
A corneal ulcer is a medical condition that affects the eye, specifically the cornea. It is characterized by an open sore or lesion on the surface of the cornea, which can be caused by various factors such as bacterial or fungal infections, viruses, or injury to the eye.
The cornea is a transparent tissue that covers the front part of the eye and protects it from harmful particles, bacteria, and other foreign substances. When the cornea becomes damaged or infected, it can lead to the development of an ulcer. Symptoms of a corneal ulcer may include pain, redness, tearing, sensitivity to light, blurred vision, and a white spot on the surface of the eye.
Corneal ulcers require prompt medical attention to prevent further damage to the eye and potential loss of vision. Treatment typically involves antibiotics or antifungal medications to eliminate the infection, as well as pain management and measures to protect the eye while it heals. In severe cases, surgery may be necessary to repair the damage to the cornea.
Corneal perforation is a serious eye condition that refers to a hole or rupture in the cornea, which is the clear, dome-shaped surface at the front of the eye. The cornea plays an important role in protecting the eye and focusing light onto the retina. A perforation can result from trauma, infection, degenerative conditions, or surgical complications. It can lead to severe vision loss or blindness if not treated promptly and properly. Treatment typically involves surgery to repair or replace the damaged cornea.
Fusariosis is a rare but serious invasive fungal infection caused by the Fusarium species, a type of filamentous fungi that are commonly found in the environment, particularly in soil and plants. The infection can affect various organs and tissues, including the lungs, sinuses, skin, nails, and internal organs such as the brain, heart, and kidneys.
Fusariosis is often difficult to diagnose due to its nonspecific symptoms and the challenges of detecting the fungus in clinical samples. The infection can occur in people with weakened immune systems, such as those undergoing chemotherapy, organ transplantation, or treatment with immunosuppressive drugs.
The severity of fusariosis varies depending on the site of infection and the patient's underlying health status. In some cases, it can cause severe illness and even death, especially in patients with prolonged neutropenia (low white blood cell count) or other serious medical conditions. Treatment typically involves antifungal medications, such as voriconazole or amphotericin B, and sometimes surgical debridement of infected tissues.
Nystatin is an antifungal medication used to treat various fungal infections such as candidiasis, which can affect the skin, mouth, throat, and vagina. It works by binding to ergosterol, a component of fungal cell membranes, creating pores that increase permeability and ultimately lead to fungal cell death.
The medical definition of Nystatin is:
A polyene antifungal agent derived from Streptomyces noursei, used primarily for topical treatment of mucocutaneous candidiasis. It has little systemic absorption and is therefore not useful for treating systemic fungal infections. Common side effects include local irritation and burning sensations at the application site.
Econazole is an antifungal medication used to treat various fungal infections of the skin, nails, and mucous membranes. It works by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes, thereby weakening the cell membrane and increasing permeability, ultimately leading to fungal cell death.
Econazole is available in various formulations, including creams, lotions, powders, and tablets. It is commonly used to treat conditions such as athlete's foot, jock itch, ringworm, candidiasis (yeast infection), and other fungal skin infections.
It is important to follow the instructions of a healthcare provider when using econazole or any medication, and to report any side effects or concerns promptly.
Filipin is not a medical term itself, but it is the name given to a group of compounds that are used in medicine and research. Medically, Filipin is often referred to as Filipin III or Filipin stain, which is a fluorescent polyene antibiotic used in the study of lipids, particularly in diagnosing certain types of lipid storage diseases such as Niemann-Pick disease type C. The Filipin stain binds to unesterified cholesterol and forms complexes that exhibit blue fluorescence under ultraviolet light. This property is used to detect the accumulation of free cholesterol in various tissues and cells, which can be indicative of certain diseases or conditions.
Antifungal agents are a type of medication used to treat and prevent fungal infections. These agents work by targeting and disrupting the growth of fungi, which include yeasts, molds, and other types of fungi that can cause illness in humans.
There are several different classes of antifungal agents, including:
1. Azoles: These agents work by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes. Examples of azole antifungals include fluconazole, itraconazole, and voriconazole.
2. Echinocandins: These agents target the fungal cell wall, disrupting its synthesis and leading to fungal cell death. Examples of echinocandins include caspofungin, micafungin, and anidulafungin.
3. Polyenes: These agents bind to ergosterol in the fungal cell membrane, creating pores that lead to fungal cell death. Examples of polyene antifungals include amphotericin B and nystatin.
4. Allylamines: These agents inhibit squalene epoxidase, a key enzyme in ergosterol synthesis. Examples of allylamine antifungals include terbinafine and naftifine.
5. Griseofulvin: This agent disrupts fungal cell division by binding to tubulin, a protein involved in fungal cell mitosis.
Antifungal agents can be administered topically, orally, or intravenously, depending on the severity and location of the infection. It is important to use antifungal agents only as directed by a healthcare professional, as misuse or overuse can lead to resistance and make treatment more difficult.
"Fusarium" is a genus of fungi that are widely distributed in the environment, particularly in soil, water, and on plants. They are known to cause a variety of diseases in animals, including humans, as well as in plants. In humans, Fusarium species can cause localized and systemic infections, particularly in immunocompromised individuals. These infections often manifest as keratitis (eye infection), onychomycosis (nail infection), and invasive fusariosis, which can affect various organs such as the lungs, brain, and bloodstream. Fusarium species produce a variety of toxins that can contaminate crops and pose a threat to food safety and human health.
Ergosterol is a steroid found in the cell membranes of fungi, which is similar to cholesterol in animals. It plays an important role in maintaining the fluidity and permeability of fungal cell membranes. Ergosterol is also the target of many antifungal medications, which work by disrupting the synthesis of ergosterol or binding to it, leading to increased permeability and eventual death of the fungal cells.
Ophthalmic solutions are sterile, single-use or multi-dose preparations in a liquid form that are intended for topical administration to the eye. These solutions can contain various types of medications, such as antibiotics, anti-inflammatory agents, antihistamines, or lubricants, which are used to treat or prevent ocular diseases and conditions.
The pH and osmolarity of ophthalmic solutions are carefully controlled to match the physiological environment of the eye and minimize any potential discomfort or irritation. The solutions may be packaged in various forms, including drops, sprays, or irrigations, depending on the intended use and administration route.
It is important to follow the instructions for use provided by a healthcare professional when administering ophthalmic solutions, as improper use can lead to eye injury or reduced effectiveness of the medication.
Allergic bronchopulmonary aspergillosis (ABPA) is a medical condition characterized by an hypersensitivity reaction to the fungus Aspergillus species, most commonly A. fumigatus. It primarily affects the airways and lung tissue. The immune system overreacts to the presence of the fungus, leading to inflammation and damage in the lungs.
The main symptoms of ABPA include wheezing, coughing, production of thick mucus, shortness of breath, and chest tightness. These symptoms are similar to those seen in asthma and other respiratory conditions. Some people with ABPA may also experience fever, weight loss, and fatigue.
Diagnosis of ABPA typically involves a combination of clinical evaluation, imaging studies (such as chest X-rays or CT scans), and laboratory tests (such as blood tests or sputum cultures) to detect the presence of Aspergillus species and elevated levels of certain antibodies.
Treatment for ABPA usually involves a combination of corticosteroids to reduce inflammation and antifungal medications to eradicate the Aspergillus infection. In some cases, immunomodulatory therapies may also be used to help regulate the immune system's response to the fungus.
It is important to note that ABPA can lead to serious complications if left untreated, including bronchiectasis (permanent enlargement of the airways), pulmonary fibrosis (scarring of the lung tissue), and respiratory failure. Therefore, prompt diagnosis and treatment are essential for managing this condition.