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FEMS Microbiology Reviews Jul 2012Streptomyces bacteria are ubiquitous in soil, conferring the characteristic earthy smell, and they have an important ecological role in the turnover of organic material.... (Review)
Review
Streptomyces bacteria are ubiquitous in soil, conferring the characteristic earthy smell, and they have an important ecological role in the turnover of organic material. More recently, a new picture has begun to emerge in which streptomycetes are not in all cases simply free-living soil bacteria but have also evolved to live in symbiosis with plants, fungi and animals. Furthermore, much of the chemical diversity of secondary metabolites produced by Streptomyces species has most likely evolved as a direct result of their interactions with other organisms. Here we review what is currently known about the role of streptomycetes as symbionts with fungi, plants and animals. These interactions can be parasitic, as is the case for scab-causing streptomycetes, which infect plants, and the Streptomyces species Streptomyces somaliensis and Streptomyces sudanensis that infect humans. However, in most cases they are beneficial and growth promoting, as is the case with many insects, plants and marine animals that use streptomycete-produced antibiotics to protect themselves against infection. This is an exciting and newly emerging field of research that will become increasingly important as the search for new antibiotics switches to unusual and under-explored environments.
Topics: Animals; Fungi; Plant Diseases; Plant Physiological Phenomena; Plants; Streptomyces; Symbiosis
PubMed: 22091965
DOI: 10.1111/j.1574-6976.2011.00313.x -
Microbial Cell Factories May 2015Marine microorganisms are an important source of new drug leads. However, the discovery and sustainable production of these compounds are often hampered due to the...
Activation and enhancement of Fredericamycin A production in deepsea-derived Streptomyces somaliensis SCSIO ZH66 by using ribosome engineering and response surface methodology.
BACKGROUND
Marine microorganisms are an important source of new drug leads. However, the discovery and sustainable production of these compounds are often hampered due to the unavailable expression of cryptic biosynthetic gene clusters or limited titer. Ribosome engineering and response surface methodology (RSM) integrated strategy was developed in this study to activate cryptic gene cluster in the deepsea-derived Streptomyces somaliensis SCSIO ZH66, and subsequently isolation, structural analysis, and the yield enhancement of the activated compound, anticancer drug lead Fredericamycin A (FDM A), were performed.
RESULTS
In order to discover novel natural products from marine Streptomyces strains by genome mining strategy, the deepsea-derived S. somaliensis SCSIO ZH66 was subject to ribosome engineering to activate the expression of cryptic gene clusters. A resistant strain ZH66-RIF1 was thereby obtained with 300 μg/mL rifampicin, which accumulated a brown pigment with cytotoxicity on MS plate while absent in the wild type strain. After screening of fermentation conditions, the compound with pigment was purified and identified to be FDM A, indicating that the activation of a cryptic FDM A biosynthetic gene cluster was taken place in strain ZH66-RIF1, and then it was identified to be ascribed to the mutation of R444H in the β subunit of RNA polymerase. To further improve the yield efficiently, nine fermentation medium components were examined for their significance on FDM A production by Plackett-Burman design and Box-Behnken design. The optimum medium composition was achieved by RSM strategy, under which the titer of FDM A reached 679.5 ± 15.8 mg/L after 7 days of fermentation, representing a 3-fold increase compared to the original medium. In terms of short fermentation time and low-cost fermentation medium, strain ZH66-RIF1 would be an ideal alternative source for FDM A production.
CONCLUSIONS
Our results would hasten the efforts for further development of FDM A as a drug candidate. Moreover, this ribosome engineering and RSM integrated methodology is effective, fast and efficient; it would be applicable to genome mining for novel natural products from other strains.
Topics: Genetic Engineering; Isoquinolines; Molecular Sequence Data; Multigene Family; Mutation; Spiro Compounds; Streptomyces
PubMed: 25927229
DOI: 10.1186/s12934-015-0244-2 -
PLoS Neglected Tropical Diseases Aug 2023Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of...
Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of mycetoma in the county, as well as to describe the main causative agents involved in the disease using methods affordable locally. Based on the data collected by the team of cooperative medicine Cirugia en Turkana (Surgery in Turkana), a specific study for mycetoma was started during the 16th humanitarian medicine campaign in February 2019. Patients with suspected mycetoma were studied at the Lodwar County Referral Hospital (LCRH). After informing the patient and getting their consent, the lesions were examined and sampled (mainly by biopsy) and clinical data were recorded. Samples were washed in sterile saline solution and cut in fragments. Some of these were inoculated on Sabouraud Dextrose Agar, Malt Extract Agar, and diluted Nutrient Agar plates. One fragment of each sample was used for DNA extraction. The DNA and the rest of the fragments of samples were kept at -20°C. All cultures were incubated at room temperature at the LCRH laboratory. The DNA obtained from clinical samples was submitted to PCR amplification of the ITS-5.8S and the V4-V5 16S rRNA gene region, for the detection and identification of fungi and bacteria respectively. From February 2019 till February 2022, 60 patients were studied. Most of them were men (43, 74,1%) between 13 and 78 y.o. (mean age 37). Half of the patients were herdsmen but, among women 40% (6) were housewives and 26.7% (4) charcoal burners. Lesions were mainly located at the feet (87.9%) and most of the patients (54; 93.1%) reported discharge of grains in the exudate, being 27 (46.6%) yellow or pale colored and 19 (32.8%) of them dark grains. Culture of clinical samples yielded 35 fungal and bacterial putative causative agents. Culture and molecular methods allowed the identification of a total of 21 causative agents of mycetoma (39.6% of cases studied). Most of them (17) corresponded to fungi causing eumycetoma (80.9%) being the most prevalent the genus Madurella (7; 41.2%), with two species involved (M. mycetomatis and M. fahalii), followed by Aspergillus (2; 11.8%). Other minority genera detected were Cladosporium, Fusarium, Acremonium, Penicillium, and Trichophyton (5.9% each of them). Actinobacteria were detected in 19.1% of samples, but only Streptomyces somaliensis was identified as a known agent of mycetoma, the rest being actinobacteria not previously described as causative agents of the disease, such as Cellulosimicrobium cellulans detected in two of the patients. Although Kenya is geographically located in the mycetoma belt, to our knowledge this is the first report on mycetoma in this country from 1973, and the first one for Turkana County.
Topics: Male; Humans; Female; Adult; Mycetoma; Kenya; Agar; RNA, Ribosomal, 16S; Polymerase Chain Reaction; Madurella
PubMed: 37578968
DOI: 10.1371/journal.pntd.0011327 -
International Journal of Surgery Case... Mar 2022Mycetoma is a neglected tropical disease that commonly affects the lower extremity. The disease is attributed to subcutaneous granulomatous inflammation leading to...
INTRODUCTION
Mycetoma is a neglected tropical disease that commonly affects the lower extremity. The disease is attributed to subcutaneous granulomatous inflammation leading to distinct clinical features of gradual painless swelling accompanied by nodules and drains. Orbital mycetoma is an extremely rare entity of the disease. We reported the clinical presentation, diagnosis, and surgical outcomes in a case of orbital mycetoma with cranial extension.
CASE PRESENTATION
A 25-years-old male complained of left eye protrusion for 8 years, followed by complete loss of vision on the left eye for 7 years and eventually left eye pain for the last year. The left eye was displaced anteriorly and inferiorly with normal oculomotor, abducent, and trochlear examination. Brain CT scan showed an increase in orbital bone thickness with extension to the anterior cranial base, middle cranial base, and the orbital process of the zygomatic bone. MRI revealed a large lesion involving the left frontotemporal region with extension to left orbit, left posterior ethmoid air cells, and left temporal suprasellar region. The lesion was homogenously enhanced with contrast. The patient underwent a left orbitozygomatic cranitomy for resection of the lesion. However, total resection was inapplicable due to the extension of the bony lesion up to the petrous bone. Cranioplasty was performed by titanium mesh.
CONCLUSION
Mycetoma is a chronic inflammatory disease affecting subcutaneous tissues commonly in the lower limbs. The disease can be caused by fungi (Eumycetoma) or bacteria (Actinomycetoma). Orbital mycetoma is an extremely rare entity of the disease. However, it is commonly associated with the cranial extension. Early diagnosis and prompt surgical and medical treatment are the keys to good outcomes.
PubMed: 35231737
DOI: 10.1016/j.ijscr.2022.106868 -
Annales de Dermatologie Et de... Jan 2003Mycetoma is a pathological process in which eumycotic (fungal) or actinomycotic causative agents from exogenous source produce grains. It follows penetrating injury...
BACKGROUND
Mycetoma is a pathological process in which eumycotic (fungal) or actinomycotic causative agents from exogenous source produce grains. It follows penetrating injury inoculating soil organisms, occurring preferentially in rural areas usually among labourers who work barefoot. Mycetoma is a localized chronic, and deforming infectious disease of subcutaneous tissues, skin and bones. We report 130 cases of mycetoma in Senegal from 1983 to 2000.
PATIENTS AND METHODS
There were 130 patients with mycetoma. Clinical diagnosis of mycetoma was based on open tract sinuses, tumefaction or discharge of grain. Diagnosis confirmation was based on mycology and histology. An X-ray was preformed to detect bone lesions. Treatment was medical for actinomycetoma and surgical for eumycetoma.
RESULTS
We observed 76 actinomycetoma and 54 eumycetoma (Sex ratio M/F=6.6; mean age=34.7 +/- 14.8 years). The mean duration before the first medical evaluation was 4.8 +/- 5.6 years. Actinomycetoma was due to Actinomadura pelletieri, (54 cases), Actinomadura madurae (17 cases) and Streptomyces somaliensis (5 cases). Eumycetoma was due to Madurella mycetomatis (38 cases), Leptospahria senegalensis (9 cases), Pseudoallescheria boydii (6 cases) and Rhinoclediella atrovirens (1 case). Clinical inflammatory features significantly associated with actinomyces (p<0.001 OR=2.64) were predominant (85 cases). Tumoral and cystic features were found in the others forms. Lesions were located on the foot in 81 patients. Bone lesions, depending on the duration, were observed in 68 patients. Neurological damage occurred in 3 patients with dorsolumbar actinomycetoma. Sixty-six patients with actinomycetoma were cured by medical treatment.
DISCUSSION
The 130 cases of mycetoma were remarkable by the long duration of the disease before the first medical evaluation. Pain and tumor were the two main symptoms which brought the patients to the hospital and had appeared after 5 years duration and the predominance of actinomadura pelletieri actinomycetoma was responsible for 41.3 p. 100 of our cases. In Niger and Mauritania, mycetoma were actinomycetoma in respectively 71.2 p. 100 and 25 p. 100 of cases. The geographic distribution of pathogenic mycetoma agents was determined by the annual rainfall. Distinction between eumycetoma and actinomycetoma is very important for the treatment.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Mycetoma; Retrospective Studies
PubMed: 12605151
DOI: No ID Found -
Indian Journal of Dermatology,... 2022Background Mycetoma is widespread in Yemen; however, there are only a few documented reports on the entity from this geographical area. Methods A prospective study of...
Background Mycetoma is widespread in Yemen; however, there are only a few documented reports on the entity from this geographical area. Methods A prospective study of 184 cases of mycetoma (male 145 and female 39) from different regions of north-western Yemen was conducted between July 2000 and May 2014. Clinical profile was recorded in a standardized protocol. The diagnosis was based on clinical features, X-ray studies, examination of grains, and histopathology. Results Eumycetoma was diagnosed in 129, caused by Madurella mycetomatis in 124, Leptosphaeria senegalensis in one and pale grain fungus in four, whereas actinomycetoma occurred in 55, caused by Streptomyces somaliensis in 29, Actinomadura madurai in nine, Actinomadura pelletieri in one, and Nocardia in sixteen. Eumycetoma cases were treated with prolonged course of antifungal drugs, mostly ketoconazole, with itraconazole being used in four patients, along with excision or debulking. Results were better when antifungal drugs were given two to three months before surgery and in those who received itraconazole. Actinomycetoma cases were initially treated with co-trimoxazole monotherapy; later streptomycin was added in 30 cases. Six patients who did not show adequate improvement and two others from the start were treated with modified Welsh regimen and with good results. Limitations Identification of different causative agents was done by histopathology and could not be reconfirmed by culture. Conclusion Mycetoma is widespread in north-western Yemen with a higher incidence of eumycetoma and a majority of the cases were caused by Madurella mycetomatis. Modified Welsh regimen in actinomycetoma and itraconazole with excision in eumycetoma showed the best results.
Topics: Antifungal Agents; Female; Humans; India; Itraconazole; Madurella; Male; Mycetoma; Prospective Studies; Yemen
PubMed: 35389029
DOI: 10.25259/IJDVL_500_2021 -
PLoS Neglected Tropical Diseases Oct 2022Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many...
INTRODUCTION
Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many devastating impacts on patients and communities. In this study, we assessed clinical findings, investigations, and predictors for recurrence of head and neck mycetoma in Sudan.
METHODOLOGY
A retrospective study was conducted at Mycetoma Research Center in Khartoum between January 1999 and December 2020 for all patients with head and neck mycetoma. Data were analyzed using R software version 4.0.2.
RESULTS
We included 107 patients with head and neck mycetoma. 65.4% were young adult males from mycetoma endemic areas in Sudan, and most of them were students (33.6%). Most of patients (64.4%) had actinomycetoma. Before presenting with head and neck mycetoma, majority (75.7%) had a long duration with mycetoma, and 30.8% had a history of trauma. The commonest invaded site was the parietal region (30.8%). The lesion started gradually in most of the patients (96.3%). 53.3% of the patients had large size lesions with no sweating, regional lymph nodes involvement, or distal vein involvement. CT scan was the most accurate diagnostic tool while 8.4% of patients were diagnosed by clinical examinations only. Laboratory investigations confirmed that 24/45 (44.4%) of actinomycetoma was caused by Streptomyces somaliensis while 13/28 (46.4%) of eumycetoma was caused by Madurella mycetomatis. All patients with recurrence of head and neck mycetoma underwent surgical excision of the lesion (n = 41/41 {100%}, p < 0.001).
CONCLUSION
In head and neck mycetoma, the most common type was actinomycetes in Sudan. Majority had a long course of mycetoma and the commonest causative organism was Streptomyces somaliensis. The treatment outcome was poor and characterized by a low cure rate.
Topics: Humans; Male; Young Adult; Madurella; Mycetoma; Retrospective Studies; Streptomyces; Sudan
PubMed: 36251632
DOI: 10.1371/journal.pntd.0010838 -
PLoS Neglected Tropical Diseases Jul 2022Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity...
Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the β-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment.
Topics: Amoxicillin; Anti-Bacterial Agents; Clavulanic Acid; Humans; Mycetoma; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 35877680
DOI: 10.1371/journal.pntd.0010128 -
PLoS Neglected Tropical Diseases Jul 2019Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative...
Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative agents organise themselves in macroscopic structures called grains. These grains are surrounded by a massive inflammatory reaction. The processes leading to this host tissue reaction and the immunophenotypic characteristics of the mycetoma granuloma are not known. Due to the massive immune reaction and the tissue remodeling involved, we hypothesised that the expression levels of interleukin-17 (IL-17) and matrix metalloprotease-9 (MMP-9) in the mycetoma granuloma formation were correlated to the severity of the disease and that this correlation was independent of the causative agent responsible for the granuloma reaction. To determine the expression of IL-17 and MMP-9 in mycetoma lesions, the present study was conducted at the Mycetoma Research Centre, Sudan. Surgical biopsies from 100 patients with confirmed mycetoma were obtained, and IL-17 and MMP-9 expression in the mycetoma granuloma were evaluated immunohistochemically. IL-17 was mainly expressed in Zones I and II, and far less in Zone III. MMP-9 was detected mainly in Zones II and III, and the least expression was in Zone I. MMP-9 was more highly expressed in Actinomadura pelletierii and Streptomyces somaliensis biopsies compared to Madurella mycetomatis biopsies. MMP-9 levels were directly proportional to the levels of IL-17 (p = 0.001). The only significant association between MMP9 and the patients' characteristics was the disease duration (p<0.001). There was an insignificant correlation between the IL-17 levels and the patients' demographic characteristics.
Topics: Actinobacteria; Actinomadura; Adolescent; Adult; Biopsy; Child; Collagen; Female; Gene Expression; Granuloma; Humans; Immunohistochemistry; Interleukin-17; Madurella; Male; Matrix Metalloproteinase 9; Middle Aged; Mycetoma; Qualitative Research; Severity of Illness Index; Streptomyces; Sudan; Young Adult
PubMed: 31295246
DOI: 10.1371/journal.pntd.0007351 -
PLoS Neglected Tropical Diseases Aug 2019Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper...
Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper treatment. In endemic areas, various diagnostic tests and techniques are in use to achieve that, and that includes grain culture, surgical biopsy histopathological examination, fine needle aspiration cytological (FNAC) examination and in certain centres molecular diagnosis such as PCR. In this retrospective study, the sensitivity, specificity and diagnostic accuracy of grain culture, surgical biopsy histopathological examination and FNAC to identify the mycetoma causative organisms were determined. The histopathological examination appeared to have better sensitivity and specificity. The histological examination results were correct in 714 (97.5%) out of 750 patients infected with Madurella mycetomatis, in 133 (93.6%) out of 142 patients infected with Streptomyces somaliensis, in 53 (74.6%) out of 71 patients infected with Actinomadura madurae and in 12 (75%) out of 16 patients infected with Actinomadura pelletierii. FNAC results were correct in 604 (80.5%) out of 750 patients with Madurella mycetomatis eumycetoma, in 50 (37.5%) out of 133 Streptomyces somaliensis patients, 43 (60.5%) out of 71 Actinomadura madurae patients and 11 (68.7%) out of 16 Actinomadura pelletierii. The mean time required to obtain the FNAC result was one day, and for the histopathological examinations results it was 3.5 days, and for grain it was a mean of 16 days. In conclusion, histopathological examination and FNAC are more practical techniques for rapid species identification than grain culture in many endemic regions.
Topics: Actinobacteria; Actinomadura; Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Madurella; Male; Middle Aged; Mycetoma; Pathology, Molecular; Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Streptomyces; Young Adult
PubMed: 31465459
DOI: 10.1371/journal.pntd.0007056