Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium tuberculosis strains, atypical mycobacteria and isocitrate lyase

2014 ◽  
Vol 53 ◽  
pp. 1-9 ◽  
Author(s):  
Martin Krátký ◽  
Jarmila Vinšová ◽  
Eva Novotná ◽  
Jiřina Stolaříková
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Isocitrate Lyase ◽  
Multidrug Resistant ◽  
Atypical Mycobacteria

scholarly journals Proteomic analysis of drug-susceptible and multidrug-resistant nonreplicating Beijing strains of Mycobacterium tuberculosis cultured in vitro

2021 ◽  
Vol 26 ◽  
pp. 100960
Author(s):  
Bhanubong Saiboonjan ◽  
Sittiruk Roytrakul ◽  
Arunnee Sangka ◽  
Viraphong Lulitanond ◽  
Kiatichai Faksri ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Proteomic Analysis ◽  
Multidrug Resistant

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Correction: In Vitro Activity of Rifampicin and Verapamil Combination in Multidrug-Resistant Mycobacterium tuberculosis

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133343 ◽  
Author(s):  
Fernanda de Oliveira Demitto ◽  
Renata Claro Ribeiro do Amaral ◽  
Flaviane Granero Maltempe ◽  
Vera Lúcia Dias Siqueira ◽  
Regiane Bertin de Lima Scodro ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity

scholarly journals Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis

2015 ◽  
Vol 59 (9) ◽  
pp. 5844-5846 ◽  
Author(s):  
Sam Ogwang ◽  
Caryn E. Good ◽  
Brenda Okware ◽  
Mary Nsereko ◽  
Michael R. Jacobs ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Pulmonary Tb ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Sub Saharan

ABSTRACTAdditional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to havein vitroactivity againstMycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40Mycobacterium tuberculosisisolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.

scholarly journals Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Mycobacterium tuberculosis Phosphoserine Phosphatase

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 415 ◽  
Author(s):  
Elise Pierson ◽  
Marie Haufroid ◽  
Tannu Priya Gosain ◽  
Pankaj Chopra ◽  
Ramandeep Singh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Metabolic Enzyme ◽  
Phosphoserine Phosphatase ◽  
Cellular Assays ◽  
Promising Target ◽  
Global Health Issue ◽  
Serine Pathway

Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen’s serine pathway, it appears to be involved in immune evasion mechanisms. In this work, a malachite green-based phosphatase assay has been used to screen 122 compounds from an internal chemolibrary. Trisubstituted harmine derivatives were found among the best hits that inhibited SerB2 activity. Synthesis of an original compound helped to discuss a brief structure activity relationship evaluation. Kinetics experiments showed that the most potent derivatives inhibit the phosphatase in a parabolic competitive fashion with apparent inhibition constants ( K i ) values in the micromolar range. Their interaction modes with the enzyme were investigated through induced fit docking experiments, leading to results consistent with the experimental data. Cellular assays showed that the selected compounds also inhibited M. tuberculosis growth in vitro. Those promising results may provide a basis for the development of new antimycobacterial agents targeting SerB2.

scholarly journals In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Manoon Leechawengwongs ◽  
Therdsak Prammananan ◽  
Sarinya Jaitrong ◽  
Pamaree Billamas ◽  
Nampueng Makhao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Concentration ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 μg/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.

scholarly journals Characteristic Resistance Mechanism ofMycobacterium tuberculosisto DC-159a, a New Respiratory Quinolone

2011 ◽  
Vol 55 (8) ◽  
pp. 3958-3960 ◽  
Author(s):  
Jun-ichiro Sekiguchi ◽  
Areeya Disratthakit ◽  
Shinji Maeda ◽  
Norio Doi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Double Mutation ◽  
Resistant Mutants ◽  
Characteristic Resistance

ABSTRACTA G88C mutation in GyrA is one of the key alterations by whichMycobacterium tuberculosismutants acquire DC-159a resistancein vitro. A novel double mutation in GyrA, G88C D94H, conferred high DC-159a resistance. Different mutation patterns in GyrA were demonstrated for DC-159a-resistant mutants and quinolone-resistant multidrug-resistant (QR-MDR)M. tuberculosisisolates, with a mutation either at position 90 or 94 and double mutations at 90 and 91 or at 90 and 94. DC-159a might be promising for QRM. tuberculosistreatment.

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