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Frontiers in Immunology 2021The mechanisms underlying -induced mycobacteriosis remain unexplored. Using head kidney macrophages (HKM) from catfish (), we report that Ca surge across...
The mechanisms underlying -induced mycobacteriosis remain unexplored. Using head kidney macrophages (HKM) from catfish (), we report that Ca surge across mitochondrial-Ca uniporter (MICU), and consequent mitochondrial ROS (mtROS) production, is imperative for mycobactericidal activity. Inhibition of mtROS alleviated HKM apoptosis and enhanced bacterial survival. Based on RNA interference (RNAi) and inhibitor studies, we demonstrate that the Toll-like receptor (TLR)-2-endoplasmic reticulum (ER) stress-store-operated calcium entry (SOCE) axis is instrumental for activating the mt-Ca/mtROS cascade in -infected HKM. Additionally, pharmacological inhibition of mtROS attenuated the expression of , , and , which suggests a positive feedback loop between ER-stress-induced SOCE and mtROS production. Elevated tumor necrosis factor alpha (TNF-α) levels and caspase-8 activity were observed in HKM consequent to infection, and our results implicate that mtROS is crucial in activating the TNF-mediated caspase-8 activation. Our results for the first time demonstrate mitochondria as an innate immune signaling center regulating mycobacteriosis in fish. We conclude that induced persistent SOCE signaling leads to mtROS production, which in turn activates the TNF-α/caspase-8 axis culminating in HKM apoptosis and bacterial clearance.
Topics: Animals; Calcium; Catfishes; Head Kidney; Macrophages; Mitochondria; Mycobacterium Infections, Nontuberculous; Mycobacterium fortuitum; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 2
PubMed: 34987503
DOI: 10.3389/fimmu.2021.748758 -
Journal of Applied Microbiology Dec 1998The rapidly growing mycobacteria (RGM) are broadly disbursed in the environment. They have been recovered from freshwater, seawater, wastewater and even potable water...
The rapidly growing mycobacteria (RGM) are broadly disbursed in the environment. They have been recovered from freshwater, seawater, wastewater and even potable water samples and are increasingly associated with non-tuberculous mycobacterial disease. There is scant evidence that non-tuberculous mycobacteria (NTM) and RGM form biofilms. Therefore, an experimental system was designed to assess the ability of RGM to form biofilms under controlled laboratory conditions. A flat plate reactor flow cell was attached to either a high or low nutrient reservoir and monitored by image analysis over time. Two surfaces were chosen for assessment of biofilm growth: silastic which is commonly used in medical settings and high density polyethylene (HDPE) which is prevalent in water distribution systems. The results show that Mycobacterium fortuitum and M. chelonae formed biofilms under both high and low nutrient conditions on both surfaces studied. These results suggest that RGM may form biofilms under a variety of conditions in industrial and medical environments.
Topics: Biofilms; Colony Count, Microbial; Mycobacterium chelonae; Mycobacterium fortuitum; Nutritional Physiological Phenomena; Polyethylene; Silicones; Time Factors; Water Microbiology
PubMed: 21182694
DOI: 10.1111/j.1365-2672.1998.tb05284.x -
Journal of the European Academy of... May 2010We describe an outbreak of Mycobacterium fortuitum cutaneous infections associated with mesotherapy in La Rioja, Spain.
OBJECTIVE
We describe an outbreak of Mycobacterium fortuitum cutaneous infections associated with mesotherapy in La Rioja, Spain.
DESIGN
Descriptive epidemiology.
SETTING
Private practice.
PATIENTS OR OTHER PARTICIPANTS
Case subjects were customers of a single beauty salon who were treated with mesotherapy injections.
INTERVENTION(S)
Two skin biopsies were taken from each patient.
RESULTS
Over the designated period, 138 women received mesotherapy. Of these women, 39, or 28.3%, developed lesions ultimately thought to be caused by Mycobacterium fortuitum infection. The number of lesions per patient varied from 3 to 20 in the most severe case. Most of the lesions were indurated, erythematous or violaceous papules, some progressing to become fluctuant boils with suppuration, fistulization and scarring. The individual lesions varied in diameter from 0.5 to 6 cm. Two patients (5.1%) developed inguinal or axillary adenopathy. Two others presented with fever. One reported muscular pain. In 12 of the 39 cases, M. fortuitum was isolated from the wound cultures. The patients were all successfully treated with clarithromycin and levofloxacin.
CONCLUSIONS
We identified a large outbreak of rapidly growing mycobacterial lesions among women who received mesotherapy injections in a single beauty salon.
Topics: Biopsy; Cosmetic Techniques; Disease Outbreaks; Female; Humans; Mycobacterium Infections; Mycobacterium fortuitum; Spain
PubMed: 19840199
DOI: 10.1111/j.1468-3083.2009.03461.x -
Antimicrobial Agents and Chemotherapy Sep 2021
Topics: Anti-Infective Agents; Antitubercular Agents; Clofazimine; Diarylquinolines; Fluoroquinolones; Microbial Sensitivity Tests; Mycobacterium fortuitum; Rifabutin; Tetracyclines
PubMed: 34280021
DOI: 10.1128/AAC.00593-21 -
Scandinavian Journal of Infectious... 1997Records of patients have been retrospectively examined studied during an 11-y period, from whom Mycobacterium fortuitum or M. chelonae was isolated in Sweden....
Records of patients have been retrospectively examined studied during an 11-y period, from whom Mycobacterium fortuitum or M. chelonae was isolated in Sweden. Respiratory isolates were obtained from 71 patients. Clinical information was accessible in 52, chest X-ray was pathological in 51, and 42 had underlying diseases. Four skin and 4 urine isolates were observed. Two cases of osteitis and 2 bone marrow isolates of M. chelonae were found. One girl had a submandibular lymph node abscess with M. fortuitum. Of 2 HIV patients, 1 had positive blood cultures with M. fortuitum and the other positive sputum culture with M. chelonae. The broad spectrum of infections with M. fortuitum complex necessitates an integrated judgement of clinical and bacteriological data to determine the relevance of such isolates.
Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Bone and Bones; Female; HIV Infections; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium chelonae; Mycobacterium fortuitum; Respiratory System; Retrospective Studies; Skin; Sweden; Urogenital System
PubMed: 9571737
DOI: 10.3109/00365549709035897 -
Journal Der Deutschen Dermatologischen... Mar 2024
Topics: Humans; Mycobacterium fortuitum; Mycobacterium Infections, Nontuberculous; Abscess
PubMed: 38185788
DOI: 10.1111/ddg.15321 -
Microbial Cell Factories Mar 20239α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a significant intermediate for the synthesis of glucocorticoid drugs. However, in the process of phytosterol...
Improving the production of 9α-hydroxy-4-androstene-3,17-dione from phytosterols by 3-ketosteroid-Δ-dehydrogenase deletions and multiple genetic modifications in Mycobacterium fortuitum.
BACKGROUND
9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a significant intermediate for the synthesis of glucocorticoid drugs. However, in the process of phytosterol biotransformation to manufacture 9-OHAD, product degradation, and by-products restrict 9-OHAD output. In this study, to construct a stable and high-yield 9-OHAD producer, we investigated a combined strategy of blocking Δ‑dehydrogenation and regulating metabolic flux.
RESULTS
Five 3-Ketosteroid-Δ-dehydrogenases (KstD) were identified in Mycobacterium fortuitum ATCC 35855. KstD2 showed the highest catalytic activity on 3-ketosteroids, followed by KstD3, KstD1, KstD4, and KstD5, respectively. In particular, KstD2 had a much higher catalytic activity for C9 hydroxylated steroids than for C9 non-hydroxylated steroids, whereas KstD3 showed the opposite characteristics. The deletion of kstDs indicated that KstD2 and KstD3 were the main causes of 9-OHAD degradation. Compared with the wild type M. fortuitum ATCC 35855, MFΔkstD, the five kstDs deficient strain, realized stable accumulation of 9-OHAD, and its yield increased by 42.57%. The knockout of opccr or the overexpression of hsd4A alone could not reduce the metabolic flux of the C22 pathway, while the overexpression of hsd4A based on the knockout of opccr in MFΔkstD could remarkably reduce the contents of 9,21 ‑dihydroxy‑20‑methyl‑pregna‑4‑en‑3‑one (9-OHHP) by-products. The inactivation of FadE28-29 leads to a large accumulation of incomplete side-chain degradation products. Therefore, hsd4A and fadE28-29 were co-expressed in MFΔkstDΔopccr successfully eliminating the two by-products. Compared with MFΔkstD, the purity of 9-OHAD improved from 80.24 to 90.14%. Ultimately, 9‑OHAD production reached 12.21 g/L (83.74% molar yield) and the productivity of 9-OHAD was 0.0927 g/L/h from 20 g/L phytosterol.
CONCLUSIONS
KstD2 and KstD3 are the main dehydrogenases that lead to 9-OHAD degradation. Hsd4A and Opccr are key enzymes regulating the metabolic flux of the C19- and C22-pathways. Overexpression of fadE28-29 can reduce the accumulation of incomplete degradation products of the side chains. According to the above findings, the MF-FA5020 transformant was successfully constructed to rapidly and stably accumulate 9-OHAD from phytosterols. These results contribute to the understanding of the diversity and complexity of steroid catabolism regulation in actinobacteria and provide a theoretical basis for further optimizing industrial microbial catalysts.
Topics: Phytosterols; Mycobacterium fortuitum; Androstenedione; Oxidoreductases; Steroids
PubMed: 36922830
DOI: 10.1186/s12934-023-02052-y -
Head & Neck Nov 2007Parotitis caused by nontuberculous mycobacteria, a very rare disease entity, has never been reported to be caused by Mycobacterium fortuitum (M. fortuitum) in the...
BACKGROUND
Parotitis caused by nontuberculous mycobacteria, a very rare disease entity, has never been reported to be caused by Mycobacterium fortuitum (M. fortuitum) in the literature.
METHODS AND RESULTS
An 8-year-old girl was seen with painful swelling of the right parotid gland despite antibiotic treatment of more than 1 month. Elevated serum amylase activity and diffuse contrast-enhanced CT of the parotid gland confirmed the diagnosis of parotitis. Histopathological study of specimens taken from the right parotid tail mass showed granulomatous inflammation with acid-fast positive bacilli; culture later confirmed M. fortuitum. After administration of clarithromycin and ciprofloxacin for 9 consecutive months, the parotitis and parotid tail mass were completely resolved at follow-up examination.
CONCLUSION
To our knowledge, this is the first case report of parotitis caused by M. fortuitum and its successful medical treatment.
Topics: Anti-Bacterial Agents; Child; Ciprofloxacin; Clarithromycin; Female; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium fortuitum; Parotitis
PubMed: 17427970
DOI: 10.1002/hed.20626 -
BMC Microbiology Feb 2009Highly pathogenic mycobacteria like Mycobacterium tuberculosis are characterised by their slow growth and their ability to reside and multiply in the very hostile...
BACKGROUND
Highly pathogenic mycobacteria like Mycobacterium tuberculosis are characterised by their slow growth and their ability to reside and multiply in the very hostile phagosomal environment and a correlation between the growth rate of mycobacteria and their pathogenicity has been hypothesised. Here, porin genes from M. fortuitum were cloned and characterised to address their impact on the growth rate of fast-growing and pathogenic mycobacteria.
RESULTS
Two genes encoding porins orthologous to MspA from M. smegmatis, porM1 and porM2, were cloned from M. fortuitum strains, which were originally isolated from human patients. Both porin genes were at least partially able to complement the mutations of a M. smegmatis mutant strain lacking the genes mspA and mspC with respect to the growth rate. PorM1 and porM2 were present in different strains of M. fortuitum including the type strain. Comparative expression analysis of porM genes revealed divergent porin expression among analysed M. fortuitum strains. Repression of the expression of porins by antisense technique decreased the growth rates of different M. fortuitum. The effects of over-expression of porM1 as well as porM2 varied depending on the strain and the concentration of antibiotic added to the medium and indicated that PorM1 and PorM2 enhance the growth of M. fortuitum strains, but also the diffusion of the antibiotic kanamycin into the cells.
CONCLUSION
This study demonstrates the important role of porin expression in growth as well as antibiotic susceptibility of the opportunistic bacterium M. fortuitum.
Topics: Amino Acid Sequence; Anti-Bacterial Agents; Cloning, Molecular; DNA, Bacterial; Gene Expression Profiling; Gene Knockdown Techniques; Gene Order; Genetic Complementation Test; Humans; Kanamycin; Molecular Sequence Data; Mutation; Mycobacterium Infections, Nontuberculous; Mycobacterium fortuitum; Mycobacterium smegmatis; Porins; Sequence Alignment; Sequence Analysis, DNA
PubMed: 19203364
DOI: 10.1186/1471-2180-9-31 -
The Journal of Bone and Joint Surgery.... May 2010
Topics: Adult; Anti-Bacterial Agents; Debridement; Humans; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium fortuitum; Orthopedic Procedures; Patellar Ligament; Reoperation; Therapeutic Irrigation
PubMed: 20439674
DOI: 10.2106/JBJS.I.01083