Mycobacterium tuberculosis Strains H37ra and H37rv have equivalent minimum inhibitory concentrations to most antituberculosis drugs

Heinrichs, M. Tobias; May, Robert Justin; Heider, Fabian; Reimers, Tobias; Sy, Sherwin K. B.; Peloquin, Charles A.; Derendorf, Hartmut

doi:10.4103/ijmy.ijmy_33_18

Cited by 54 publications

(39 citation statements)

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“…The front-line (or primary) anti-TB drugs were used as positive control ( Table 1 ). Determined MIC values for antibiotics were in general agreement with literature data for M. tuberculosis H37Ra strain [ 7 ].…”

Section: Resultssupporting

confidence: 81%

Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model

et al. 2018

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The purpose of the study was to evaluate the antimycobacterial activity and the possible action mode of cinnamon bark essential oil and its main constituent—cinnamaldehyde—against the Mycobacterium tuberculosis ATCC 25177 strain. Cinnamaldehyde was proved to be the main bioactive compound responsible for mycobacterial growth inhibition and bactericidal effects. The antimycobacterial activity of cinnamaldehyde was found to be comparable with that of ethambutol, one of the first-line anti-TB antibiotics. The selectivity index determined using cell culture studies in vitro showed a high biological potential of cinnamaldehyde. In M. tuberculosis cells exposed to cinnamaldehyde the cell membrane stress sensing and envelope preserving system are activated. Overexpression of clgR gene indicates a threat to the stability of the cell membrane and suggests a possible mechanism of action. No synergism was detected with the basic set of antibiotics used in tuberculosis treatment: ethambutol, isoniazid, streptomycin, rifampicin, and ciprofloxacin.

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Section: Resultssupporting

confidence: 81%

Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model

et al. 2018

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“…The mutant construction and drug susceptibility testing were performed in BSL2 laboratory following institutional biosafety procedures. The reason we used the avirulent M. tuberculosis H37Ra strain is because it is a good surrogate of its virulent parent strain H37Rv in terms of drug susceptibility profiles (Heinrichs et al, 2018). Briefly, the Rv1258c gene was amplified with its adjacent 1 kb fragment on both sides from M. tuberculosis genomic DNA and cloned into p2NIL plasmid vector.…”

Section: Methodsmentioning

confidence: 99%

Mutations in Efflux Pump Rv1258c (Tap) Cause Resistance to Pyrazinamide, Isoniazid, and Streptomycin in M. tuberculosis

et al. 2019

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Although drug resistance in Mycobacterium tuberculosis is mainly caused by mutations in drug activating enzymes or drug targets, there is increasing interest in the possible role of efflux in causing drug resistance. Previously, efflux genes have been shown to be upregulated upon drug exposure or implicated in drug resistance in overexpression studies, but the role of mutations in efflux pumps identified in clinical isolates in causing drug resistance is unknown. Here we investigated the role of mutations in efflux pump Rv1258c (Tap) from clinical isolates in causing drug resistance in M. tuberculosis. We constructed point mutations V219A and S292L in Rv1258c in the chromosome of M. tuberculosis and the point mutations were confirmed by DNA sequencing. The susceptibility of the constructed M. tuberculosis Rv1258c mutants to different tuberculosis drugs was assessed using conventional drug susceptibility testing in 7H11 agar in the presence and absence of efflux pump inhibitor piperine. A C14-labeled PZA uptake experiment was performed to demonstrate higher efflux activity in the M. tuberculosis Rv1258c mutants. Interestingly, the V219A and S292L point mutations caused clinically relevant drug resistance to pyrazinamide (PZA), isoniazid (INH), and streptomycin (SM), but not to other drugs in M. tuberculosis. While V219A point mutation conferred low-level drug resistance, the S292L mutation caused a higher level of resistance. Efflux inhibitor piperine inhibited INH and PZA resistance in the S292L mutant but not in the V219A mutant. The S292L mutant had higher efflux activity for pyrazinoic acid (the active form of PZA) than the parent strain. We conclude that point mutations in the efflux pump Rv1258c in clinical isolates can confer clinically relevant drug resistance, including PZA resistance, and could explain some previously unaccounted drug resistance in clinical strains. Future studies need to take efflux mutations into consideration for improved detection of drug resistance in M. tuberculosis and address their role in affecting treatment outcome in vivo .

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“…Unfortunately, the broad-spectrum activity shown by both clofazimine and bedaquiline is not universal with all anti-TB therapeutics. Many novel agents (such as DC-159a, SQ-641, and tigecycline) have variable activity against mycobacteria at best, while the antimicrobial activity of other compounds appears to be limited to either M. tuberculosis (such as delamanid and pretomanid) [152] or NTM (such as clarithromycin and cycloserine) [153,154,155]. Active testing of TB-specific drugs for anti-NTM activity, and vice versa, may provide a wealth of potential therapeutic options for both diseases, but must be approached with some caution.…”

Section: Cross-fertilization Between Tb and Ntm Development Programsmentioning

confidence: 99%

Inhaled Antibiotics for Mycobacterial Lung Disease

Banaschewski¹,

Hofmann²

2019

Pharmaceutics

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Mycobacterial lung diseases are an increasing global health concern. Tuberculosis and nontuberculous mycobacteria differ in disease severity, epidemiology, and treatment strategies, but there are also a number of similarities. Pathophysiology and disease progression appear to be relatively similar between these two clinical diagnoses, and as a result these difficult to treat pulmonary infections often require similarly extensive treatment durations of multiple systemic drugs. In an effort to improve treatment outcomes for all mycobacterial lung diseases, a significant body of research has investigated the use of inhaled antibiotics. This review discusses previous research into inhaled development programs, as well as ongoing research of inhaled therapies for both nontuberculous mycobacterial lung disease, and tuberculosis. Due to the similarities between the causative agents, this review will also discuss the potential cross-fertilization of development programs between these similar-yet-different diseases. Finally, we will discuss some of the perceived difficulties in developing a clinically utilized inhaled antibiotic for mycobacterial diseases, and potential arguments in favor of the approach.

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Mycobacterium tuberculosis Strains H37ra and H37rv have equivalent minimum inhibitory concentrations to most antituberculosis drugs

Cited by 54 publications

References 0 publications

Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model

Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model

Mutations in Efflux Pump Rv1258c (Tap) Cause Resistance to Pyrazinamide, Isoniazid, and Streptomycin in M. tuberculosis

Inhaled Antibiotics for Mycobacterial Lung Disease

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