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International Journal of Molecular... Mar 2023Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical... (Review)
Review
Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered mycolicibacterial strains has been effectively enhanced by sterol core metabolic modification. In recent years, research on the non-core metabolic pathway of steroids (NCMS) in mycolicibacterial strains has made significant progress. This review discusses the molecular mechanisms and metabolic modifications of NCMS for accelerating sterol uptake, regulating coenzyme I balance, promoting propionyl-CoA metabolism, reducing reactive oxygen species, and regulating energy metabolism. In addition, the recent applications of biotechnology in steroid intermediate production are summarized and compared, and the future development trend of NCMS research is discussed. This review provides powerful theoretical support for metabolic regulation in the biotransformation of phytosterols.
Topics: Fermentation; Mycobacteriaceae; Biotechnology; Phytosterols; Steroids; Biotransformation; Metabolic Networks and Pathways; Androstenedione
PubMed: 36982310
DOI: 10.3390/ijms24065236 -
Emerging Infectious Diseases Mar 2021Severe Mycolicibacter kumamotonensis-pulmonary disease was diagnosed in a 68-year-old immunocompetent woman in Greece; the disease was initially treated as tuberculosis....
Severe Mycolicibacter kumamotonensis-pulmonary disease was diagnosed in a 68-year-old immunocompetent woman in Greece; the disease was initially treated as tuberculosis. The patient responded favorably to a new treatment regimen of azithromycin, amikacin, moxifloxacin, and linezolid. Complete symptom resolution and radiologic improvement resulted.
Topics: Aged; Anti-Bacterial Agents; Female; Greece; Humans; Lung Diseases; Mycobacteriaceae; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 33622489
DOI: 10.3201/eid2703.191648 -
Medicine Feb 2022Mycobacterium peregrinum is a member of the group of rapidly growing nontuberculous mycobacteria. It mainly causes surgical site and catheter-related infections, while...
RATIONALE
Mycobacterium peregrinum is a member of the group of rapidly growing nontuberculous mycobacteria. It mainly causes surgical site and catheter-related infections, while pulmonary infection is rare. We herein present a case of pulmonary infection caused by M peregrinum.
PATIENT CONCERNS
A 62-year-old woman visited our hospital with dyspnea and was admitted for the treatment of pneumonia in July 2018.
DIAGNOSIS
Chest computed tomography showed patchy opacities and consolidation in the bilateral lungs and a cavity in the right upper lobe, which persisted after the treatment of bacterial pneumonia 5 years ago. She was administered ceftriaxone and azithromycin. Consolidation in the bilateral lungs improved, whereas the cavity in the right upper lobe remained and the consolidation surrounding it gradually spread. On admission, the sputum acid-fast bacillus culture was positive, and M peregrinum was identified twice by mass spectrometry. The cavity and consolidation surrounding it were diagnosed as pulmonary mycobacteriosis caused by M peregrinum.
INTERVENTIONS
Although we recommended treatment for mycobacteriosis, the patient refused it.
OUTCOMES
The patient is regularly followed up; however, the cavity wall is thickening and shadows have become mildly enhanced over the course of 3 years.
LESSONS
We herein present a rare case of pulmonary mycobacteriosis caused by M peregrinum and discuss the literature. Since limited information is currently available on pulmonary mycobacteriosis caused by M peregrinum, the accumulation of further case reports and the clarification of its clinical features are needed.
Topics: Female; Humans; Lung; Middle Aged; Mycobacteriaceae; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Radiography; Tomography, X-Ray Computed
PubMed: 35147117
DOI: 10.1097/MD.0000000000028809 -
Internal Medicine (Tokyo, Japan) Oct 2021Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the...
Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.
Topics: Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Nontuberculous Mycobacteria
PubMed: 33896860
DOI: 10.2169/internalmedicine.5300-20 -
The European Respiratory Journal Jul 2019
Topics: Humans; Lung Diseases; Mycobacterium Infections; Mycobacterium abscessus; Nontuberculous Mycobacteria
PubMed: 31296786
DOI: 10.1183/13993003.01149-2019 -
Frontiers in Public Health 2020Nontuberculous mycobacteria (NTM) that cause human disease can be isolated from household tap water. Easy-to-use physical methods to reduce NTM from this potential...
Nontuberculous mycobacteria (NTM) that cause human disease can be isolated from household tap water. Easy-to-use physical methods to reduce NTM from this potential source of exposure are needed. Filters and UV disinfection have been evaluated for their ability to reduce numbers of waterborne non-NTM organisms from drinking water, but their efficacy in reducing NTM counts are not well-established. Thus, five commercially available disinfection methods were evaluated for their potential as practical, efficient, and low-cost methods to reduce NTM from tap water. First, suspensions of tap water-adapted were passed through either a point-of-use, disposable, 7-day or 14-day Pall-Aquasafe filter. The 7-day filter prevented passage of in effluent water for 13 days, and the 14-day filter prevented the passage of for 25 days. Second, a granular activated carbon filter system failed to significantly reduce and numbers. Third, suspensions of tap water-adapted , and ("MycoCocktail") were passed through the "LifeStraw GO" hollow-fiber, two-stage membrane filtration system. LifeStraw GO prevented passage of the MycoCocktail suspension for the entire 68-day evaluation period. Finally, two different water bottle UV sterilization systems, "Mountop" and "SteriPEN," were evaluated for their capacity to reduce NTM numbers from tap water. Specifically, MycoCocktail suspensions were dispensed into Mountop and SteriPEN water bottles and UV treated as per the manufacturer instructions once daily for 7 days, followed by a once weekly treatment for up to 56 days. After 4 days of daily UV treatment, both systems achieved a >4 log reduction in MycoCocktail CFU. After the 56-day evaluation period, suspension and biofilm-associated CFU were measured, and a >4 log reduction in CFU was maintained in both systems. Taken together, physical disinfection methods significantly reduced NTM numbers from tap water and may be easy-to-use, accessible applications to reduce environmental NTM exposures from drinking water.
Topics: Disinfection; Humans; Mycobacterium abscessus; Mycobacterium avium; Nontuberculous Mycobacteria; Water
PubMed: 32596197
DOI: 10.3389/fpubh.2020.00190 -
Scientific Reports Mar 2024Mycobacterial pathogens present a significant challenge to disease control efforts globally due to their inherent resistance to multiple antibiotics. The rise of...
Molecular docking, molecular dynamics simulations and binding free energy studies of interactions between Mycobacterium tuberculosis Pks13, PknG and bioactive constituents of extremophilic bacteria.
Mycobacterial pathogens present a significant challenge to disease control efforts globally due to their inherent resistance to multiple antibiotics. The rise of drug-resistant strains of Mycobacterium tuberculosis has prompted an urgent need for innovative therapeutic solutions. One promising way to discover new tuberculosis drugs is by utilizing natural products from the vast biochemical space. Multidisciplinary methods can used to harness the bioactivity of these natural products. This study aimed to evaluate the antimycobacterial efficacy of functional crude extracts from bacteria isolated from gold mine tailings in South Africa. Bacterial strains were identified using 16S rRNA sequencing. The crude extracts obtained from the bacteria were tested against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc155, and Mycobacterium aurum A+. Untargeted HPLC-qTOF and molecular networking were used to identify the functional constituents present in extracts that exhibited inhibitory activity. A virtual screening workflow (VSW) was used to filter compounds that were strong binders to Mycobacterium tuberculosis Pks13 and PknG. The ligands returned from the VSW were subjected to optimization using density functional theory (DFT) at M06-2X/6-311++ (d,p) level of theory and basis set implemented in Gaussian16 Rev.C01. The optimized ligands were re-docked against Mycobacterium tuberculosis Pks13 and PknG. Molecular dynamics simulation and molecular mechanics generalized born surface area were used to evaluate the stability of the protein-ligand complexes formed by the identified hits. The hit that showed promising binding characteristics was virtually modified through multiple synthetic routes using reaction-driven enumeration. Three bacterial isolates showed significant activity against the two strains of Mycobacterium, while only two, Bacillus subtilis and Bacillus licheniformis, exhibited activity against both Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc155, and Mycobacterium aurum A+. The tentatively identified compounds from the bacterial crude extracts belonged to various classes of natural compounds associated with antimicrobial activity. Two compounds, cyclo-(L-Pro-4-OH-L-Leu) and vazabitide A, showed strong binding against PknG and Pks13, with pre-MD MM-GBSA values of - 42.8 kcal/mol and - 47.6 kcal/mol, respectively. The DFT-optimized compounds exhibited the same docking scores as the ligands optimized using the OPSL-4 force field. After modifying vazabitide A, its affinity to the Pks13 binding site increased to - 85.8 kcal/mol, as revealed by the post-MD MM-GBSA analysis. This study highlights the potential of bacteria isolates from gold mine tailings as a source of new scaffolds for designing and optimizing anti-Mycobacterium agents. These agents synthesized in-silico can be further tested in-vitro to evaluate their efficacy.
Topics: Mycobacterium tuberculosis; Molecular Dynamics Simulation; Molecular Docking Simulation; RNA, Ribosomal, 16S; Anti-Bacterial Agents; Mycobacterium smegmatis; Biological Products; Complex Mixtures; Antitubercular Agents; Mycobacteriaceae
PubMed: 38514663
DOI: 10.1038/s41598-024-57124-9 -
PLoS Neglected Tropical Diseases Aug 2017Mycobacteriaceae comprises pathogenic species such as Mycobacterium tuberculosis, M. leprae and M. abscessus, as well as non-pathogenic species, for example, M.... (Comparative Study)
Comparative Study
Mycobacteriaceae comprises pathogenic species such as Mycobacterium tuberculosis, M. leprae and M. abscessus, as well as non-pathogenic species, for example, M. smegmatis and M. thermoresistibile. Genome comparison and annotation studies provide insights into genome evolutionary relatedness, identify unique and pathogenicity-related genes in each species, and explore new targets that could be used for developing new diagnostics and therapeutics. Here, we present a comparative analysis of ten-mycobacterial genomes with the objective of identifying similarities and differences between pathogenic and non-pathogenic species. We identified 1080 core orthologous clusters that were enriched in proteins involved in amino acid and purine/pyrimidine biosynthetic pathways, DNA-related processes (replication, transcription, recombination and repair), RNA-methylation and modification, and cell-wall polysaccharide biosynthetic pathways. For their pathogenicity and survival in the host cell, pathogenic species have gained specific sets of genes involved in repair and protection of their genomic DNA. M. leprae is of special interest owing to its smallest genome (1600 genes and ~1300 psuedogenes), yet poor genome annotation. More than 75% of the pseudogenes were found to have a functional ortholog in the other mycobacterial genomes and belong to protein families such as transferases, oxidoreductases and hydrolases.
Topics: Bacterial Proteins; Genome, Bacterial; Mycobacteriaceae; Virulence Factors
PubMed: 28854187
DOI: 10.1371/journal.pntd.0005883 -
Bulletin of the World Health... 1973Some criteria are presented to help evaluate papers appearing in the literature claiming successful cultivation of M. leprae either in the absence or in the presence of... (Review)
Review
Some criteria are presented to help evaluate papers appearing in the literature claiming successful cultivation of M. leprae either in the absence or in the presence of tissue-cultured cells. Recently, electron microscopic studies have definitely shown M. leprae to belong to the genus Mycobacterium and its division to occur through transverse section. A survey is given of the mycobacterial strains isolated in the last 10 years from leprosy lesions. These strains belong to taxonomically different species and cannot be considered to be M. leprae. No substantiated claim was made concerning the in vitro growth of M. leprae and the application of the tissue culture technique has been equally disappointing. The view is expressed that progress towards the in vitro cultivation of M. leprae can be made only as a result of increased knowledge about the intracellular environment and the metabolic activities of this organism, to be obtained by the application of modern biochemical and histochemical techniques.
Topics: Animals; Bacteriological Techniques; Cell Division; Cell Line; Cells, Cultured; Culture Media; Culture Techniques; Ganglia; Haplorhini; Humans; L Forms; Leprosy; Macrophages; Mice; Microscopy, Electron; Mycobacterium; Mycobacterium leprae; Mycobacterium lepraemurium; Rats
PubMed: 4212439
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Letters Aug 2023A series of 2-(tetrazol-5-yl)sulfonylacetamide derivatives were synthesized and evaluated for their in vitro inhibitory activity against Mycobacterium tuberculosis (Mtb)...
A series of 2-(tetrazol-5-yl)sulfonylacetamide derivatives were synthesized and evaluated for their in vitro inhibitory activity against Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). The most active compounds exhibited in vitro MIC values of 1.25 μg/mL against Mtb, but they were less effective against Mm (MIC ≥ 10 μg/mL). Despite the most active compounds having favourable physicochemical properties and one of them having a half-life of ∼3 h when incubated with mouse liver microsomes, two representative highly active compounds showed strong chemical reactivity to cysteine derivatives, as surrogate in vivo sulfur-centred nucleophiles, indicating excessive electrophilicity, and therefore, likely indiscriminate chemical reactivity in vivo, representing an unacceptably high risk of general toxicity, and low likelihood of being therapeutically effective.
Topics: Animals; Mice; Mycobacterium tuberculosis; Antitubercular Agents; Mycobacterium marinum; Microbial Sensitivity Tests; Structure-Activity Relationship
PubMed: 37369331
DOI: 10.1016/j.bmcl.2023.129391