scholarly journals Enhanced Bactericidal Effects of Pyrazinamide Toward Mycobacterium smegmatis and Mycobacterium tuberculosis upon Conjugation to a {Au(I)-triphenylphosphine}+ Moiety

ACS Omega ◽  
2020 ◽  
Vol 5 (12) ◽  
pp. 6826-6833 ◽  
Author(s):  
Jenny Stenger-Smith ◽  
Mireille Kamariza ◽  
Indranil Chakraborty ◽  
Ramatoulaye Ouattara ◽  
Carolyn R. Bertozzi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Bactericidal Effects

scholarly journals Protective and Therapeutic Efficacy of Mycobacterium smegmatis Expressing HBHA-hIL12 Fusion Protein against Mycobacterium tuberculosis in Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31908 ◽  
Author(s):  
Shanmin Zhao ◽  
Yong Zhao ◽  
Fengfeng Mao ◽  
Caiqin Zhang ◽  
Bing Bai ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fusion Protein ◽  
Mycobacterium Smegmatis ◽  
Therapeutic Efficacy

scholarly journals Expression of Mycobacterium smegmatisPyrazinamidase in Mycobacterium tuberculosis Confers Hypersensitivity to Pyrazinamide and Related Amides

2000 ◽  
Vol 182 (19) ◽  
pp. 5479-5485 ◽  
Author(s):  
Helena I. M. Boshoff ◽  
Valerie Mizrahi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Localization ◽  
Wild Type ◽  
Gene Encoding ◽  
Allelic Exchange ◽  
Mutant Strains ◽  
Established Role ◽  
Amidase Gene

ABSTRACT A pyrazinamidase (PZase)-deficient pncA mutant ofMycobacterium tuberculosis, constructed by allelic exchange, was used to investigate the effects of heterologous amidase gene expression on the susceptibility of this organism to pyrazinamide (PZA) and related amides. The mutant was highly resistant to PZA (MIC, >2,000 μg/ml), in accordance with the well-established role ofpncA in the PZA susceptibility of M. tuberculosis (A. Scorpio and Y. Zhang, Nat. Med. 2:662–667, 1996). Integration of the pzaA gene encoding the major PZase/nicotinamidase from Mycobacterium smegmatis (H. I. M. Boshoff and V. Mizrahi, J. Bacteriol. 180:5809–5814, 1998) or the M. tuberculosis pncA gene into the pncAmutant complemented its PZase/nicotinamidase defect. In bothpzaA- and pncA-complemented mutant strains, the PZase activity was detected exclusively in the cytoplasm, suggesting an intracellular localization for PzaA and PncA. ThepzaA-complemented strain was hypersensitive to PZA (MIC, ≤10 μg/ml) and nicotinamide (MIC, ≥20 μg/ml) and was also sensitive to benzamide (MIC, 20 μg/ml), unlike the wild-type andpncA-complemented mutant strains, which were highly resistant to this amide (MIC, >500 μg/ml). This finding was consistent with the observation that benzamide is hydrolyzed by PzaA but not by PncA. Overexpression of PzaA also conferred sensitivity to PZA, nicotinamide, and benzamide on M. smegmatis (MIC, 150 μg/ml in all cases) and rendered Escherichia colihypersensitive for growth at low pH.

scholarly journals Effects of clofazimine on planktonic and biofilm growth of Mycobacterium tuberculosis and Mycobacterium smegmatis

2015 ◽  
Vol 3 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Maborwa T. Mothiba ◽  
Ronald Anderson ◽  
Bernard Fourie ◽  
Willem A. Germishuizen ◽  
Moloko C. Cholo
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Biofilm Growth

scholarly journals Hypoxanthine-Guanine Phosphoribosyltransferase Is Dispensable for Mycobacterium smegmatis Viability

2019 ◽  
Vol 202 (5) ◽  
Author(s):  
Zdeněk Knejzlík ◽  
Klára Herkommerová ◽  
Dana Hocková ◽  
Iva Pichová
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Model Organism ◽  
Specific Inhibitor ◽  
Purine Salvage ◽  
Content Type ◽  
Acyclic Nucleoside Phosphonates ◽  
Hypoxanthine Guanine Phosphoribosyltransferase

ABSTRACT Purine metabolism plays a ubiquitous role in the physiology of Mycobacterium tuberculosis and other mycobacteria. The purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is essential for M. tuberculosis growth in vitro; however, its precise role in M. tuberculosis physiology is unclear. Membrane-permeable prodrugs of specifically designed HGPRT inhibitors arrest the growth of M. tuberculosis and represent potential new antituberculosis compounds. Here, we investigated the purine salvage pathway in the model organism Mycobacterium smegmatis. Using genomic deletion analysis, we confirmed that HGPRT is the only guanine and hypoxanthine salvage enzyme in M. smegmatis but is not required for in vitro growth of this mycobacterium or survival under long-term stationary-phase conditions. We also found that prodrugs of M. tuberculosis HGPRT inhibitors displayed an unexpected antimicrobial activity against M. smegmatis that is independent of HGPRT. Our data point to a different mode of mechanism of action for these inhibitors than was originally proposed. IMPORTANCE Purine bases, released by the hydrolytic and phosphorolytic degradation of nucleic acids and nucleotides, can be salvaged and recycled. The hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which catalyzes the formation of guanosine-5′-monophosphate from guanine and inosine-5′-monophosphate from hypoxanthine, represents a potential target for specific inhibitor development. Deletion of the HGPRT gene (Δhgprt) in the model organism Mycobacterium smegmatis confirmed that this enzyme is not essential for M. smegmatis growth. Prodrugs of acyclic nucleoside phosphonates (ANPs), originally designed against HGPRT from Mycobacterium tuberculosis, displayed anti-M. smegmatis activities comparable to those obtained for M. tuberculosis but also inhibited the Δhgprt M. smegmatis strain. These results confirmed that ANPs act in M. smegmatis by a mechanism independent of HGPRT.

scholarly journals Development of a Biocontrol Method Applying Bacteriophage-Containing Aerosol against Mycobacterium tuberculosis Using the Bacteriophage BTCU-1 and M. smegmatis as Models

2019 ◽  
Vol 7 (8) ◽  
pp. 237 ◽  
Author(s):  
Chun-Chieh Tseng ◽  
Dan Chi Chang ◽  
Kai-Chih Chang
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Culture Medium ◽  
Recovery Rates ◽  
Disinfection Methods ◽  
Alternative Approach ◽  
Chamber Study ◽  
Surface Decontamination ◽  
Bactericidal Efficiency

The application of bacteriophages for biocontrol has attracted increasing attention. Here, we applied ϕBTCU-1 as a model phage to develop a method for controlling Mycobacterium tuberculosis (MTB) by using a bacteriophage-containing aerosol in a chamber study. The soil-isolated ϕBTCU-1 can infect both MTB and Mycobacterium smegmatis. Our study used M. smegmatis as an MTB surrogate for safety reasons. Among all the evaluated air samplers, the Andersen impactor was chosen to evaluate the bactericidal efficiency of ϕBTCU-1 against M. smegmatis since the recovery rates of the Andersen impactor were 1.5 to 10.6 times higher than those of sampling filters. When airborne ϕBTCU-1 with the highest concentration of 109 PFU/m3 challenged M. smegmatis (105 CFU/m3) for 10 s, no M. smegmatis colony was recovered from the culture medium. For surface decontamination, no colony of M. smegmatis, which started at 1000 CFU/plate (63.6 cm2), was recovered when exposed to higher ϕBTCU-1 concentrations (>109 PFU/m3) for 60 min. Bacteriophages may be useful for reducing MTB contamination in the air or on hard surfaces. The method we have established suggests that the biocontrol method may be an alternative approach or may be combined with other disinfection methods to prevent MTB infection.

scholarly journals Features of the biochemistry of Mycobacterium smegmatis, as a possible model for Mycobacterium tuberculosis

2020 ◽  
Vol 13 (9) ◽  
pp. 1255-1264 ◽  
Author(s):  
Joseph Antony Sundarsingh T ◽  
Ranjitha J ◽  
Aiswarya Rajan ◽  
Vijayalakshmi Shankar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis
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