Tuberculosis: Today's researches—tomorrow's therapies

@article{Singh2018TuberculosisTR,
  title={Tuberculosis: Today's researches—tomorrow's therapies},
  author={Amit Singh and Avadhesha Surolia},
  journal={IUBMB Life},
  year={2018},
  volume={70}
}
Tuberculosis remains a major public health problem inflicting 1.5–2.0 million deaths annually, which is greater than the fatalities observed for all the other infectious diseases taken together and a third of world’s population harbors latent Mycobacterium tuberculosis (Mtb) burden. Its treatment and eradication are complicated by the emergence of multi drug resistant (MDR) and eXtreme drug resistant (XDR) strains of Mtb. Hence, there is an urgent need to enrich antitubercular pipeline and an… 
Multidrug-resistant strains of Mycobacterium complex species in Egyptian farm animals, veterinarians, and farm and abattoir workers
TLDR
There is a growing risk for isolation of MDR-TB from raw milk and lymph nodes of field tuberculin positive cattle as well as sputum of veterinarians and workers existed in farms and abattoirs.

References

SHOWING 1-10 OF 22 REFERENCES
Recent advances for identification of new scaffolds and drug targets for Mycobacterium tuberculosis
TLDR
This review will discuss recent progress made in the field of TB drug development with emphasis on screening methods and drug targets from M. tuberculosis, and provides insights into mechanism of action of new scaffolds that are being evaluated in various stages of clinical trials.
Mycobacterium tuberculosis: Surviving and Indulging in an Unwelcoming Host
TLDR
The history of tuberculosis, its pathology and recent advances in basic understanding of the machinery are summarized, with eventual gape on the novel therapeutic strategies emerged in the past decade.
The association between sterilizing activity and drug distribution into tuberculosis lesions
TLDR
An alternative working model is proposed to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs, and it is suggested that lesion penetration may contribute to treatment outcome.
Drug permeation and metabolism in Mycobacterium tuberculosis: Prioritising local exposure as essential criterion in new TB drug development
TLDR
Advances in analytical models and technologies which have enabled investigations of drug metabolism and pharmacokinetics (DMPK) for new TB drug development are discussed and the potential to shift the focus of traditional pharmacokinetic–pharmacodynamic analyses away from plasma to a more specific “site of action” drug exposure as an essential criterion for drug development and the design of dosing strategies is considered.
Pharmacokinetic Evaluation of the Penetration of Antituberculosis Agents in Rabbit Pulmonary Lesions
TLDR
Though further refinement is needed to accurately predict the behavior of these drugs in human subjects, the results enable the integration of lesion-specific pharmacokinetic-pharmacodynamic (PK-PD) indices in clinical trial simulations and in in vitro PK-PD studies with M. tuberculosis.
Ethambutol Partitioning in Tuberculous Pulmonary Lesions Explains Its Clinical Efficacy
TLDR
Ethambutol accumulates in diseased tissues and penetrates the major human-like lesion types represented in the rabbit model of TB disease with a lesion-to-plasma exposure ratio ranging from 9 to 12, demonstrating the critical importance of effective lesion penetration for anti-TB drugs.
Redox‐guided small molecule antimycobacterials
TLDR
A number of small molecules that have either been designed to induce redox stress or were found to do so after their discovery are reviewed and offer scope for exploration of potentially new mechanism of action.
Host heme oxygenase‐1: Friend or foe in tackling pathogens?
TLDR
The role of HMOX1 is described in pathogenesis of bacterial infections caused by Mycobacterium species, Salmonella and in microbial sepsis and the role is elaborated in viral infections such as AIDS, hepatitis, dengue, and influenza.
Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis
TLDR
The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part in M. tuberculosis killing by the drug.
Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development
TLDR
The current knowledge on PstP, PKnA, PknB and PknG based on the genetic, biochemical, and functional studies in M. tuberculosis physiopathology is reviewed to explore the potential of these molecules as targets for therapeutic intervention and discuss the advancement made in the development of inhibitors against these targets.
...
1
2
3
...