Sporothrix Sp Research Articles

Esporotricose felina: Sinais clínicos e prevenção em animais e humanos

Sporotrichosis is a mycosis caused by the fungus Sporothrix sp, which is found in plants, trees, and soil, associated with decomposing plant remains. The disease can affect various species, especially felines which, in turn, are the main transmitters of sporotrichosis to humans. Infection by Sporothrix sp. occurs through contact between injured skin and surfaces contaminated with the fungus, or scratching or biting by diseased animals. In addition to the skin manifestation, sporotrichosis can also occur in extracutaneous form, affecting multiple organs such as the lungs, lymph nodes, liver, spleen and kidneys. There is no preventive vaccine for the disease and it is treated with synthetic fungistatic agents with a broad spectrum of antifungal activity. Sporotrichosis is considered one of the most relevant mycoses in veterinary medicine and an underdiagnosed zoonosis, mainly due to the lack of control and prevention initiatives, which consequently leads to a lack of public awareness. In the states of Pernambuco, Rio de Janeiro and in some cities in states of São Paulo, Minas Gerais Bahia, Rio Grande do Norte and Paraíba have compulsory notification of cases. Since December 1, 2020, the notification of sporotrichosis in dogs and cats has become mandatory in the city of São Paulo. The purpose of this review is to emphasize that sporotrichosis is an emerging zoonosis that is underdiagnosed in Brazil. Information and publicity campaigns are needed to reinforce the importance of treatment and the potential for a cure, as well as effective educational measures related to public health programs for the control of human and animal sporotrichosis. Responsible pet ownership campaigns, which emphasize the importance of neutering and restricting street access, are of paramount importance for the epidemiological control of the disease. Veterinarians have a fundamental role to play in guiding the guardian, emphasizing that the lack of treatment, in addition to causing great suffering to the affected animal, can contribute to the spread of the disease, including to humans.

Cutaneous Sporotrichosis of Face with Verrucous Lesions over Nose, Successfully Treated with a Combination of Itraconazole and Terbinafine: A Case Report.

Dear Editor, A 13-year-old boy presented with nasal erythematous, crusted, confluent papules, and nodules persisting for approximately 35 days [Figure 1]. The patient denied contact with sick cats but mentioned playing in the bushes. The clinical diagnosis was cutaneous sporotrichosis, and he started treatment with itraconazole 100 mg per day, which was administered orally for 10 days and then increased to 200 mg per day. The exudate from the skin lesions was directly examined by a potassium hydroxide test, which was negative for fungal presence. At 25°C, a mycosal media culture of the exudate revealed colonies resembling Sporothrix sp, which appeared membranous, beige, wrinkled, and with a blackened halo [Figure 2]. At 37°C, phenotypic reversal for creamy colonies with beige and colorless verse was observed, thus demonstrating dimorphism. The lactophenol cotton blue stain revealed hyaline septate hyphae [Figure 3]. On day 44 of itraconazole treatment alone, the lesions became severely crusted, demonstrating no improvements. Thus, 250 mg of oral terbinafine was added to the treatment regimen. On day 60 of itraconazole use, a skin biopsy was performed. Grocott silver stain revealed rare samples of fungal structures [Figure 4]. Histopathology showed acanthosis of the epidermis, areas with perivascular mononuclear inflammatory infiltrate and fibrosis [Figure 5]. On day 226 of itraconazole and day 182 of terbinafine use, clinical improvement was noted, indicating the end of oral antifungal drugs [Figure 6]. The patient underwent Laser Erbium YAG, an ablative laser, to achieve favorable aesthetic results for the scar and uniformization of the skin of the nasal region.Figure 1: Infiltrated erythematous nodules of sporotrichosis on the nose with verrucous appearanceFigure 2: Culture at 25°C, showing colonies of membranous, beige, wrinkled with a blackened halo, resembling Sporothrix speciesFigure 3: The hyaline septate hyphae of Sporothrix spp. with one pyriform microconidia in daisy arrangement (lactophenol cotton blue stain, ×40)Figure 4: Grocott silver stain presenting a fungal structures (40x)Figure 5: Acanthosis of the epidermis, areas with perivascular mononuclear inflammatory infiltrate, and intense remodeling of dermal collagen with fibrosis. (H and E, 10x)Figure 6: Clinical improvement after terbinafine and itraconazole use. Only residual erythema, papules and nodulesSporotrichosis is a subcutaneous mycosis caused by a thermodimorphic fungus, Sporothrix spp., most commonly S. brasiliensis, S. schenckii, and S. globosa.[1] The lesions manifest in different clinical forms: mainly lymphocutaneous, fixed, cutaneous, disseminated, and extracutaneous. Recently, the incidence of various diseases caused by Sporothrix has been increasing in Brazil, particularly a high disease rate in urban areas. Felines have been reported as a new source of infection that spreads diseases.[2] Itraconazole is a first-line treatment for Sporothrix, but some strains, mainly S. brasiliensis, are resistant.[3–5] Moreover, itraconazole content sometimes does not match the concentrations indicated by manufacturers.[3] Itraconazole has certain pharmacokinetic concerns because of several drug interactions. For example, a high gastric pH reduces its bioavailability. Terbinafine is an alternative drug that can effectively treat cutaneous sporotrichosis, and it is affordable and has fewer interactions with other drugs.[1,4,5] To improve therapeutic outcome, itraconazole has been combined with a second drug and demonstrated good results, for example, with supersaturated potassium iodide (SSKI) solution.[6] SSKI is an alternative for cutaneous forms, which is primarily used for infants. However, compared with terbinafine, SSKI has side effects and issues, such as a lack of standardized commercial formulation and unknown mechanisms of action.[1,4] Studies describing the use of itraconazole with terbinafine are limited. In vitro, terbinafine and itraconazole have synergistic effects because both disrupt ergosterol synthesis in the cell membrane of fungi at different stages. This mechanism is beneficial due to accelerated response against chromoblastomycosis, onychomycosis, and sporotrichosis, where facial lesions can cause aesthetic stigmas and affect the quality of life of patients. In conclusion, the combination of terbinafine and itraconazole can effectively inhibit disease progression faster and thus prevent excessive fibrosis and scars.[5,7–10] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Ocular lesions in cats diagnosed with systemic sporotrichosis.

To describe the most common ocular lesions and demonstrate the frequency of ophthalmic involvement in a group of cats with systemic sporotrichosis. Two hundred seventy-four cats diagnosed with systemic sporotrichosis. The inclusion criteria included previous positive cytopathological examination, histopathological examination, or fungal culture. In a prospective case-control study, 274 cats diagnosed with systemic sporotrichosis underwent ophthalmic evaluation and received treatment for systemic sporotrichosis. Of these animals, 63 had ocular abnormalities which were recorded, and conjunctivitis was scored from 0 to 5. Diagnostic techniques utilized included fungal culture, as well as cytopathological (10 eyes; 10 cats), and histopathological examination of the palpebral conjunctiva and eyes (2 eyes). Cytopathological and histopathological examination of the conjunctiva, as well as fungal culture, proved to be important tests for the detection of Sporothrix sp. Five cats without the evidence of ophthalmic abnormalities also had a positive fungal culture. The identified ocular lesions in animals with systemic sporotrichosis included increased serous discharge (79 eyes; 53 cats), blepharoconjunctivitis (33 eyes; 25 cats), conjunctivitis (39 eyes, 20 cats), blepharitis (9 eyes; 8 cats), uveitis (5 eyes; 3 cats), and Florida keratopathy-like lesions (2 eyes; 1 cat). Sporotrichosis should be considered a differential diagnosis for conjunctivitis and blepharoconjunctivitis, especially in endemic areas. Fungal culture and cytopathology of ocular discharge and histopathological examinations of the conjunctiva are important for the diagnosis of ophthalmic sporotrichosis, although not all cats underwent laboratory testing in this study. Ocular discharge could be a source of contagion transmission.

Nested PCR for the Diagnosis of Feline Sporotrichosis From Formalin-Fixed and Paraffin-Embedded Samples Using Different DNA Extraction Protocols.

Sporotrichosis is a chronic, cosmopolitan granulomatous mycosis that affects humans and animals. The infection is caused by the dimorphic fungi Sporothrix sp. The aims of the present study were to evaluate, standardize and validate a nested PCR technique using two DNA purification kits for the extraction of DNA from formalin fixed and paraffin-embedded tissues (FFPE) for Sporothrix sp. detection. FFPE mycological culture pellet samples of different Sporothrix species (S. chilensis, S. mexicana, S. pallida, S. globosa, S. brasiliensis and S. schenckii) were used as positive controls and clinical FFPE tissue samples of animals positive for Cryptococcus sp., Leishmania infantum and Histoplasma sp. were used as negative controls. Ten clinical FFPE skin samples from cats with sporotrichosis were used to validate the nested PCR. These samples were cut into two distinct paraffin sectioning protocols (5 and 16 μm thick). The paraffin sections were subjected to two different DNA extraction kits (chemical and thermal extractions). A nested PCR was performed on the extracted DNA to identify the genus Sporothrix. The chemical extraction protocol with the 5 μm thick paraffin section was more effective in extracting DNA from Sporothrix sp. from FFPE samples and the nested PCR technique showed the highest sensitivities (100% in the positive controls and of 50% in the skin samples of cats) and specificity (100%). Therefore, the nested PCR using this protocol has great potential to be applied in Sporothrix sp. diagnosis in FFPE samples of cats.

Extracellular Vesicles from Sporothrix Yeast Cells.

Sporotrichosis is an emerging deep mycosis and a public health concern in Brazil. This mycosis is caused by the traumatic inoculation of several species of Sporothrix from nature. However, when cats transmit the disease to humans as zoonotic transmission, severe extracutaneous manifestations are observed. Therefore, effective control of the disease requires the engagement of host receptors by pathogen-derived molecules to stimulate the immune response. In this context, extracellular vesicles from Sporothrix sp contribute to intracellular communication with host cells. In addition, however, extracellular vesicles may contribute to the spread of this fungus via delivering molecules such as proteins, nucleic acids, and lipids. Thus, understanding mechanisms behind extracellular vesicles related to Sporothrix may provide us with a way to understand and identify its capacity to manipulate the host immune system and spread the infection.

Metabolites from antarctic marine-derived Sporothrix sp. SF-7266

극한환경 미생물은 극한 환경에 생존하기 위하여 특이 생존 기작을 가진다. 이는 특이 효소와 같은 특이적 대사물질 및 신규활성물질의 발현을 가능하게 한다. 이에 따라 남극 해양 유래 Sporothrix sp. SF-7266 으로 부터 특이적 대사물질 연구를 수행하였다. 다양한 chromatography 기법을 이용한 분리 및 정제를 수행하여 총 4개의 순수화합물 citromycetin, citromycin, sulochrin과 penstyrylpyrone를 단리하였다. 분리된 물질의 구조는 NMR과 MS를 통하여 규명하였다. 4개 물질 모두 다양한 생리활성 효능이 보고된 바 있으며, 특히, penstyrylpyrone은 kavalactone 계열의 구조로, 향정신성 효능이 있을 것으로 기대되며, 이를 기반으로 생리활성 규명을 진행 중이다.

Mannose-Binding Lectin and Mannose-Binding Lectin-Associated Serine Protease-2 Genotypes and Serum Levels in Patients with Sporotrichosis.

Mannose-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are important proteins in the lectin pathway of the immune system. Mannose-binding lectin and MASP-2 deficiencies have been reported to be responsible for various fungal infections. We investigated the association of MBL and MASP-2 variants with sporotrichosis in a Chinese population and revealed one rare heterozygous mutation in a disseminated cutaneous patient without immunosuppressive conditions (MASP2, p.156_159dupCHNH). We also found that sporotrichosis patients had decreased levels of MBL and MASP-2 in their serum samples compared with controls. Our findings linked, for the first time, MASP-2 deficiencies with susceptibility to Sporothrix sp.

Associação de itraconazol e iodeto de potássio no tratamento da esporotricose disseminada em um felino em Palotina, PR – relato de caso

Sporotrichosis is a zoonosis caused by a fungus of the Sporothrix gender, and transmitted through open wounds. Because of their closed territorial nature, intact male cats are most frequently affected. We describe the treatment of an adult, rescued intact male cat presented with disseminated ulcerative skin lesions affecting face, ears, neck, thoracic limb, and scapular region. Cytology of the lesions revealed the presence of macrophages containing a large number of oval oblong yeast structures consistent with Sporothrix sp. The cat was treated with once a day oral administration of itraconazole (100mg/cat) and potassium iodide (5mg/kg). Full remission was observed 126 days after beginning of treatment.

Antimicrobial Production Using Endophytic Fungus Sporothrix sp. LBKURCC43 by Carbon and Nitrogen Modification

Endophytes are endosymbiont organisms that can produce antimicrobial compounds. Media composition is one of the main components to produce industrial compounds. This study investigated the optimal media composition for antimicrobial production by endophytic fungus Sporothrix sp. LBKURCC43. The media were modified by applying composition combination between corn, potato, and sweet potato as carbon sources, and soybean and beef meat as nitrogen sources; incubation times of the fermentation were 5, 10, 15, 20, and 25 days. Antibacterial activity against pathogenic microorganisms (Escherichia coli, Staphylococcus aureus, and Candida albicans) was examined by using the agar diffusion method. A phytochemical test was conducted for determining the highest antibacterial activity. The results showed compounds produced in modified medium MM 03 (potato and soybean) had the highest inhibition zone diameter (8.09 ± 0.62 mm) at 20 days of incubation against E. coli (the ratio between potato and soybean for the medium was 3.60: 0.24). While MM 05 (corn, potato, and soybean at a ratio of 1.8: 1.8: 0.24) indicated the highest inhibition zone against S. aureus (6.03 ± 0.82 mm) at day 20. None of the compound in the modified medium was active against C. albicans. In conclusion, there were varies abilities of endophytic fungus in producing antimicrobial compounds based on their growth medium composition. The highest activity against E. Coli was obtained in the medium consisted of potato and soybean. The phytochemical test indicated the modified medium (MM 05) contained a compound that was categorized as saponin.

Uji Bioaktivitas Antibakteri Senyawa murni dari Jamur Endofit Sporothrix sp Terhadap Bakteri Escherichia coli dan Staphylococcus aureus

Modern medicines that are developing now come from active ingredients isolated from plants that require large amounts of plants. The development of new drugs from endophytic fungi found obstacles in the amount of pure compounds produced. Therefore further research is needed by using endophytic fungi as a new antimicrobial producer. This study aims to see the ability or activity of pure compounds produced by Sporothrix sp endophytic fungi from Dahlia tuber (Dahlia variabilis). Test the activity of pure compounds produced by Sporothrix sp. Endophytic fungi on E. coli and Staphylococcus aureus determined by disc diffusion method. With doses of 10, 30 and 50μg/disk. In Escherichia coli bacteria doses 10 and 50μg/disk gave significant inhibition of pure compounds from isolation compared to the positive control of ciprofloxacin, which was marked by a statistically significant test result (p <0.05). In contrast to Staphylococcus aureus there was no significant difference in doses of both doses of 10.30 and 50μg/disk. Determination of pure compounds was carried out by HPLC and Infra Red Spectrophotometry.

Esporotricosis cutánea. Informe de casos.

Introducción. La esporotricosis es una micosis profunda causada por inoculación traumática del complejo dimorfo Sporothrix sp, causando lesiones que pueden presentarse como nódulos o gomas y tener aspecto polimorfo. Tiene distribución cosmopolita. Guatemala posee focos endémicos.
 Material y métodos. Estudio descriptivo, retrospectivo, realizado en la Unidad de Dermatologia y el Departamento de Patología del Hospital General San Juan de Dios (HGSJD) de Guatemala, que incluye pacientes evaluados durante el periodo de enero 2014 a julio 2018, con diagnóstico clínico de esporotricosis y con muestras enviadas para cultivo y para estudio histopatológico.
 Resultados. Once pacientes fueron analizados, de los cuales 7 eran de sexo masculino (63.6%). La edad media fue de 49 años; En 45.5% de los pacientes, las lesiones afectaban miembros superiores. Clínicamente predominaron las formas fijas (81.8%). El 100% tuvo cultivo positivo para Sporothrix sp. En el estudio histológico se encontraron estructuras compatibles con esporotricosis en 27.28%.
 Conclusiones. En la actualidad las formas fijas son cada vez más comunes. El cultivo continúa siendo el método diagnóstico de elección para esporotricosis.

Esporotricose óssea em gato causada por Sporothrix brasiliensis

Background: Sporotrichosis is a deep cutaneous mycosis caused by the Sporothrix species complex, dimorphic fungi of which at least five are of clinical importance: S. brasiliensis, S. globosa, S. luriei, S. mexicana, and S. schenckii sensu stricto. The disease affects humans and animals, especially cats, which can manifest a wide spectrum of clinical sings, from cutaneous-lymphatic involvement to disseminated form. Infection usually results from direct inoculation of the fungus into skin. Zoonotic transmission is associated with scratching or biting of sick cats. The aim of this work was to report an atypical case of bone sporotrichosis in a cat.Case: A 5-year-old, male, neutered, mongrel and indoor cat was present at the Veterinary Clinic Hospital, Federal University of Rio Grande do Sul (HCV-UFRGS), Porto Alegre, Brazil, with lameness and increased volume in the left hindlimb. The animal had been treated intermittently with itraconazole during the last three years due to another cutaneous lesion which was recurrent and undiagnosed. A firm and painful mass was found in tarsal region of left hindlimb, that had approximately 5 cm in diameter. Radiographic examination of the left tibial-tarsal joint revealed bone lysis in the fifth metatarsal calcaneus, in addition to periosteum proliferation in calcaneus, tibio-tarsal subluxation, presence of osteophytes in tarsal bones and increase in soft tissue volume. Histopathological analysis of the biopsied tissue showed piogranulomatous inflammation. No yeast-like structures were observed in cytopathological exam. Tissue fragments were plated and Sporothrix sp. complex growth in mycological culture (Sabouraud Cycloheximide Chloramphenicol Agar). Physiological tests (growth rate at different temperatures and assimilation of sucrose and raffinose) were conducted for the differentiation of the species of complex. Molecular identification was performed using panfungal primers (ITS3-F / ITS4-R). The diagnosis of bone sporotrichosis caused by Sporothrix brasiliensis was based on clinical signs, mycological (confirmed by isolation and identification in culture medium) and molecular methods. Treatment was based on excision of the limb associated with oral administration of itraconazole and silymarin for two months. Unfortunately, three months later new nodules were seen at the abdomen and biopsy samples were positive in a new fungal culture for Sporothrix sp. Oral treatment was then restarted for four months. The cat is now free of lesions for six months and clinical monitoring visit is usually done once per month.Discussion: Sporotrichosis is a fungal infection with worldwide distribution, mostly in tropical and subtropical countries, characterized by cutaneous and subcutaneous lesions with regional lymphocutaneous dissemination, but some pulmonary and systemic infections in human have been reported. Cats are frequently infected with sporotrichosis in Brazil and develop a scattered cutaneous condition. On the other hand, the systemic form of the disease have been more observed with a disseminated respiratory or systemic condition, including infection of the lungs, liver, spleen, kidney, testis, eyes, bones, central nervous system, gastrointestinal tract, and mammary glands may also be affected. The occurrence of bone sporotrichosis, without skin lesions, show the high susceptibility of these animals to infection by Sporothrix. Molecular methods for the differentiation of Sporothrix complex are needed when the conventional methodology (histopathology and culture) does not allow the identification of the agent. The reference standard for diagnosing sporotrichosis is microscopic characterization of the pathogen isolated in culture. In our study, although the culture was positive, PCR was necessary for detecting and identifying Sporothrix brasiliensis. The reported case of bone sporotrichosis emphasizes the importance of a conclusive and differential diagnosis in feline lytic bone lesions based on the detection of fungal in the tissue by molecular methods associated with the isolation of the agent in a fungal culture.

OPTIMASI PRODUKSI DAN IDENTIFIKASI SENYAWA ANTIMIKROB DARI JAMUR ENDOFIT Sporothrix sp LBKURCC43 TANAMAN DAHLIA (Dahlia variabilis)

Dahlia tubers contain fungus Sporothrix sp which have antimicrobial activity.The objective of this research was to determine the agitation that effect the activity of antimicrobial in malt extract broth (MEB). The result showed that agitation of 150 rpm have the antimicrobial activity against Staphylococcus aureus with 21.0 mm and Escherichia colii with 12.8 mm. The identification of function group showed the extract contained O-H, C=O and Amide with UV and IR spectroscopy.

Chromoblastomycosis and sporotrichosis in Madagascar : Epidemiology, molecular diagnostic and perspectives

Introduction Chromoblastomycosis (CBM) and sporotrichosis (SP) are endemic mycosis in Madagascar that occurred following injury and telluric contamination. CBM is mostly due to Fonsecaea pedrosoi or Cladophialophora carrionii and affects usually the subcutaneous tissue, whereas SP is caused by Sporothrix schenckii by invading the lymphatic system of the arms and legs. These fungal infections are considered neglected diseases because of poor resources allocated to their diagnosis, monitoring or prevention. Objectives The general objective was to assess the current prevalence of these mycosis in Madagascar. The specific objectives were to characterize the causative fungal species and their habitat in order to prevent contamination, and to set up a sustainable clinical and laboratory network to allow proper case management and to provide a molecular-based species identification. Methods The study comprised a prospective clinical study that started in March 2013. Patients were recruited during field investigations and consultations provided in a dermatology department. Pus, biopsy and squamous were sampled from the lesions. Informed consent from the patients and ethical approval from the Ministry of Health were obtained. Histopathological and mycological analysis (direct examination and culture on Sabouraud-Cycloheximide) were performed. We have developed a PCR-based strategy that was validated on reference strains provided by BCCM/IHEM (Belgian Coordinated Collections of Micro organism). First, two sets of universal primers (NL-1/NL4 and ITS5/ITS4) were used to confirm the fungal origin of the lesions. Then, specific primers (SSHF31/SSHR97, Fon-F/Fon-R, EdF/EdR) were used for fungal species identification. Results Ninety two patients were enrolled. Mean age was 38.7 years and men were predominant with 71.7 % of cases. Overall, 47.8 % were farmers, 30.4 % self-employed, 12.0 % students and 9.8 % unemployed. Clinically, 32.6 % of cases were suspected having CBM and presented with crusted, verrucous and tumoral lesions ; 34.8 % of cases were suspected having SP characterized mainly by ulcerative and nodular lesions of the lymphatic system of the lower limbs. Mycological analysis confirmed 33 cases of SP and 13 cases of CBM. The molecular diagnosis confirmed 34 Sporothrix sp, leading to a SP prevalence of 37 % and 1 Cladophialophora sp and 16 Fonsecaea sp leading to a CBM prevalence of 18.5 %. One mycetoma probably of bacterial origin was also diagnosed. CBM cases were predominant in the north-east, east and south part of the island, whereas SP cases were located mainly in the central highlands. Conclusion These results confirmed that CBM and SP persist at a high frequency in Madagascar. The availability of a reliable PCR tool in routine and the clinical expertise gained during this study will help the national authorities to set up a proper control and prevention program. An environmental survey is planned to describe the spread of the causative agents in the environment in an attempt to prevent the contamination.

Chemical constituents from the mangrove endophytic fungus Sporothrix sp.

Chemical constituents from the mangrove endophytic fungus Sporothrix sp.

Aquastatin C, a new glycoaromatic derivative from Sporothrix sp. FN611

Bacterial fatty acid synthesis (FAS) is an attractive antibacterial target, as FAS is organized differently in bacteria and mammals.1, 2 Fatty acid biosynthesis in bacteria is crucial for the production of a number of lipid-containing components, including the cell membrane. The bacterial fatty acid system (FAS II) uses discrete monofunctional enzymes, which operate in conjunction with acyl carrier protein (ACP)-associated substrates, whereas mammalian fatty acid synthase (FAS I) is mediated by a single multifunctional enzyme–ACP complex. The differences in prokaryote and eukaryote fatty acid biosynthesis provide an attractive opportunity for selective FAS II inhibition, which is a potential strategy for the development of antibacterial agents. Bacterial enoyl-ACP reductase, which catalyzes the final and rate-limiting step in type II FAS, has been validated as a novel target for the development of antibacterial drugs.3, 4 Three isoforms, FabI, FabK and FabL, have been detected in enoyl-ACP reductase. Most of bacteria including Staphylococcus aureus contain FabI, but Streptococcus pneumonia has FabK. Enterococcus faecalis and Pseudomonas aeruginosa were known to contain both FabI and FabK, whereas Bacillus subtilis contains both FabI and FabL. InhA is the FabI homolog from Mycobacterium tuberculosis. Indeed, the antibacterial target of triclosan5 and isoniazid,6 which are currently used antibacterial agents, have been determined to be the FabI and InhA, respectively. Therefore, the enoyl-ACP reductase inhibitors may prove to be interesting lead compounds for the development of effective antibacterial drugs.

Aquastatin A, a New Inhibitor of Enoyl-Acyl Carrier Protein Reductase from Sporothrix sp. FN611

Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Sporothrix sp. FN611 potently inhibited the enoyl-ACP reductase (FabI) of Staphylococcus aureus. Its structure identified the metabolite as aquastatin A by the MS and NMR data. Aquastatin A inhibited S. aureus FabI with an IC(50) of 3.2 microM. It also prevented the growth of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration of 16-32 microg/ml. Aquastatin A also exerted an inhibitory effect against the FabK isoform, an enoyl-ACP reductase of Streptococcus pneumoniae, with an IC(50) of 9.2 microM. The degalactosylation of aquastatin A did not affect the FabI and FabK-inhibitory or antibacterial activities, thereby suggesting that the sugar moiety within its molecular structure was not involved in these activities. The inhibitory effects of aquastatin A and its degalactosylated derivative on enoyl-ACP reductases and bacterial viability are reported for the first time in this study; these effects point to the potential that aquastatin A may be developed into a new broad-spectrum antibacterial and anti-MRSA agent.

Cytologic diagnosis of generalized cutaneous sporotrichosis in a hunting hound

A 1-year-old male Foxhound/Walker Hound mix was presented to the small animal internal medicine service at Louisiana State University School of Veterinary Medicine with a 6-week history of progressive, multifocal, ulcerative and draining, well-circumscribed lesions in a generalized distribution. Prior to referral, a presumptive diagnosis was made of sterile pyogranulomatous disease; immunosuppressive therapy was instituted but resulted in clinical deterioration. At presentation, the dog had marked neutropenia (1100 neutrophils/microL), and a mild toxic left shift (400 bands/microL). Cytologic findings in the exudates from a draining skin lesion included high numbers of markedly degenerate neutrophils (about 95% of nucleated cells) as well as low numbers of macrophages, small mature lymphocytes, and eosinophils. Low numbers of intracellular (within neutrophils and macrophages) and extracellular, pleomorphic, cigar-to-ovoid shaped organisms ( approximately 3x9 microm) consistent with Sporothrix were observed. Histopathologic examination of a skin biopsy showed marked, chronic, active, ulcerative, pyogranulomatous dermatitis and panniculitis, with intralesional yeast consistent with Sporothrix sp. The etiologic agent was confirmed as Sporothrix schenckii by macerated tissue fungal culture. The patient was treated with itraconazole, enrofloxacin, and clindamycin, with clinical resolution occurring over a 3-month period. This case is a rare example of the cytologic diagnosis of Sporothrix schenckii in a canine patient. Diagnosis of canine sporotrichosis is often challenging and usually requires tissue culture, as infected dogs typically harbor very few organisms. The patient's prior immunosuppressive therapy likely contributed to higher numbers of organisms in exudates from the cutaneous lesions, facilitating cytologic diagnosis.

ChemInform Abstract: Chlovalicin, a New Cytocidal Antibiotic Produced by Sporothrix sp. FO‐ 4649. Part 2. Physicochemical Properties and Structural Elucidation.

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Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. I. Taxonomy, fermentation, isolation and biological activities.

Selective growth inhibition against IL-6 dependent cells was detected in fermentation extracts of a fungal strain FO-4649 which was characterized as Sporothrix species. An active metabolite (1) termed chlovalicin was isolated together with ovalicin and two other ovalicin derivatives (compounds 3 and 4). Chlovalicin, a ovalicin derivative with a chlorinated methylene moiety at the C-1 position of the cyclohexane ring, dose-dependently inhibited the growth of IL-6 dependent MH60 cells (IC50, 7.5 microM) in the presence of 0.2 U/ml IL-6 and, to a lesser extent, the growth of B16 melanoma cells (IC50, 38 microM). Among the other three compounds, only ovalicin showed inhibitory activity (IC50, 27 microM) against MH60 cells. These four compounds did not show any antimicrobial activity at a concentration of 1000 micrograms/ml.