How Mycobacterium tuberculosis drug resistance has shaped anti-tubercular drug discovery

Bhagwat, Amala; Deshpande, Aditi; Parish, Tanya

doi:10.3389/fcimb.2022.974101

Cited by 6 publications

(4 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of tuberculosis requires combination therapy, with isoniazid, rifampin, pyrazinamide and ethambutol being common first-line treatments. For each drug, a target-site mutation can cause resistance 81 ; for example, a recent study documented the structural basis for resistance to pyrazinamide, whereby mutation of residues near the active site of PanD impair affinity and residence time of the active prodrug, resulting in resistance 82 .…”

Section: Target Alteration Modification and Protectionmentioning

confidence: 99%

Molecular mechanisms of antibiotic resistance revisited

et al. 2022

View full text Add to dashboard Cite

Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the pipeline. Understanding the molecular mechanisms that bacteria use to resist the action of antimicrobials is critical to recognize global patterns of resistance and to improve the use of current drugs, as well as for the design of new drugs less susceptible to resistance development and novel strategies to combat resistance. In this Review, we explore recent advances in understanding how resistance genes contribute to the biology of the host, new structural details of relevant molecular events underpinning resistance, the identification of new resistance gene families and the interactions between different resistance mechanisms. Finally, we discuss how we can use this information to develop the next generation of antimicrobial therapies.

show abstract

Section: Target Alteration Modification and Protectionmentioning

confidence: 99%

Molecular mechanisms of antibiotic resistance revisited

et al. 2022

View full text Add to dashboard Cite

show abstract

“…When creating unique drug candidates and new regimens, nonspecific causes of resistance like increased efflux or lower permeability need to be considered. [49] Figure 9 shows the conceptual structural map of the GCC-TB literature. It displays the co-word analysis based on the bibliographic information obtained from the Scopus database using Hierarchical Stochastic Clustering.…”

Section: Author Abstract and Conceptual Structural Mapmentioning

confidence: 99%

“…When creating unique drug candidates and new regimens, nonspecific causes of resistance like increased efflux or lower permeability need to be considered. [ 49 ]…”

Section: Author Abstract and Conceptual Structural Mapmentioning

confidence: 99%

Tuberculosis research advances and future trends: A bibliometric knowledge mapping approach

Abdelwahab,

Taha,

Albasheer

et al. 2024

Medicine

View full text Add to dashboard Cite

The Gulf Cooperation Council (GCC) countries are more vulnerable to many transmissible diseases, including tuberculosis (TB). This study is to identify the scientific publications related to TB in the GCC countries using topic modeling and co-word analysis. A bibliometric analytic study. The R-package, VOSviewer software, IBM SPPS, and Scopus Analytics were used to analyze performance, hotspots, knowledge structure, thematic evolution, trend topics, and inter-gulf and international cooperation on TB in the past 30 years (1993–2022). A total of 1999 publications associated with research on GCC-TB were published. The annual growth rate of documents was 7.76%. Saudi Arabia is the most highly published, followed by the United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain. The most-cited GC country is Kingdom Saudi Arabia, followed by Kuwait. One hundred sixty research institutions contributed to the dissemination of TB-related knowledge in the GCC, where the highest publishing organizations were King Saud University (Kingdom Saudi Arabia; n = 518). The number of publications related to TB is high in GCC Countries. The current tendencies indicated that GCC scholars are increasingly focused on deep learning, chest X-ray, molecular docking, comorbid covid-19, risk factors, and Mycobacterium bovis.

show abstract

“…Tuberculosis (TB) remains notoriously difficult to treat and, until the COVID-19 pandemic, was the leading cause of death by a single infectious agent, Mycobacterium tuberculosis (Mtb) ( WHO, 2021 ). TB requires lengthy combination therapy to prevent the acquisition of heritable drug resistance [addressed by others in this collection, including ( Bhagwat et al., 2022 ; Jones et al., 2022 ; Liebenberg et al., 2022 )] and to effectively target inherent heterogeneity in infection that results in drug tolerance to prevent treatment failure and subsequent disease relapse ( Fox et al., 1999 ; Kerantzas and Jacobs, 2017 ). Genotypic resistance is defined by the heritable ability to grow in the presence of high concentrations of antibiotics beyond the minimum inhibitory concentration (MIC) ( Balaban et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Tools to develop antibiotic combinations that target drug tolerance in Mycobacterium tuberculosis

Greenstein

Aldridge²

2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Combination therapy is necessary to treat tuberculosis to decrease the rate of disease relapse and prevent the acquisition of drug resistance, and shorter regimens are urgently needed. The adaptation of Mycobacterium tuberculosis to various lesion microenvironments in infection induces various states of slow replication and non-replication and subsequent antibiotic tolerance. This non-heritable tolerance to treatment necessitates lengthy combination therapy. Therefore, it is critical to develop combination therapies that specifically target the different types of drug-tolerant cells in infection. As new tools to study drug combinations earlier in the drug development pipeline are being actively developed, we must consider how to best model the drug-tolerant cells to use these tools to design the best antibiotic combinations that target those cells and shorten tuberculosis therapy. In this review, we discuss the factors underlying types of drug tolerance, how combination therapy targets these populations of bacteria, and how drug tolerance is currently modeled for the development of tuberculosis multidrug therapy. We highlight areas for future studies to develop new tools that better model drug tolerance in tuberculosis infection specifically for combination therapy testing to bring the best drug regimens forward to the clinic.

show abstract

How Mycobacterium tuberculosis drug resistance has shaped anti-tubercular drug discovery

Cited by 6 publications

References 89 publications

Molecular mechanisms of antibiotic resistance revisited

Molecular mechanisms of antibiotic resistance revisited

Tuberculosis research advances and future trends: A bibliometric knowledge mapping approach

Tools to develop antibiotic combinations that target drug tolerance in Mycobacterium tuberculosis

Contact Info

Product

Resources

About