scholarly journals Growth medium and nitric oxide alter Mycobacterium abscessus morphotype and virulence

2021 ◽  
Vol 253 ◽  
pp. 126887
Author(s):  
Nishant Nandanwar ◽  
Joy E. Gibson ◽  
Michael N. Neely
2020 ◽  
Vol 19 (2) ◽  
pp. 225-231 ◽  
Author(s):  
Lea Bentur ◽  
Michal Gur ◽  
Moshe Ashkenazi ◽  
Galit Livnat-Levanon ◽  
Marko Mizrahi ◽  
...  

2020 ◽  
Vol 2 (9) ◽  
Author(s):  
Kristijan Bogdanovski ◽  
Trisha Chau ◽  
Chevalia J. Robinson ◽  
Sandra D. MacDonald ◽  
Ann M. Peterson ◽  
...  

Introduction. Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro. Methods. In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient’s isolate and comparison clinical isolates and quantified by Hill’s slopes calculated from time–kill curves. Results. M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient’s isolate was found to be the least susceptible strain in vitro. Conclusion. These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.


2019 ◽  
Vol 309 (5) ◽  
pp. 307-318 ◽  
Author(s):  
Nanthapon Ruangkiattikul ◽  
Doris Rys ◽  
Ketema Abdissa ◽  
Manfred Rohde ◽  
Torsten Semmler ◽  
...  

2019 ◽  
Vol 140 ◽  
pp. 9-17 ◽  
Author(s):  
Rajesh Kumar Tewari ◽  
Nele Horemans ◽  
Robin Nauts ◽  
Jean Wannijn ◽  
May Van Hees ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Jae-Hun Ahn ◽  
Ji-Yeon Park ◽  
Dong-Yeon Kim ◽  
Tae-Sung Lee ◽  
Do-Hyeon Jung ◽  
...  

Mycobacterium abscessus (MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-β treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/β receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-β treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-β before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-β did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-β gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-β treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.


Author(s):  
Abdi Ghaffari ◽  
Joas Lucas da Silva ◽  
Kristijan Bogdanovski ◽  
Adrian M. Zelazny ◽  
Kenneth N Olivier

Author(s):  
Dale E. McClendon ◽  
Paul N. Morgan ◽  
Bernard L. Soloff

It has been observed that minute amounts of venom from the brown recluse spider, Loxosceles reclusa, are capable of producing cytotoxic changes in cultures of certain mammalian cells (Morgan and Felton, 1965). Since there is little available information concerning the effect of venoms on susceptible cells, we have attempted to characterize, at the electron microscope level, the cytotoxic changes produced by the venom of this spider.Cultures of human epithelial carcinoma cells, strain HeLa, were initiated on sterile, carbon coated coverslips contained in Leighton tubes. Each culture was seeded with approximately 1x105 cells contained in 1.5 ml of a modified Eagle's minimum essential growth medium prepared in Hank's balanced salt solution. Cultures were incubated at 36° C. for three days prior to the addition of venom. The venom was collected from female brown recluse spiders and diluted in sterile saline. Protein determinations on the venom-were made according to the spectrophotometric method of Waddell (1956). Approximately 10 μg venom protein per ml of fresh medium was added to each culture after discarding the old growth medium. Control cultures were treated similarly, except that no venom was added. All cultures were reincubated at 36° C.


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