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Drug Resistance in Tuberculosis: Mechanisms, Diagnosis, New Responses, and the Need for an Integrated Approach

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Tuberculosis

Summary

Despite the global efforts done in recent decades, tuberculosis (TB)’s impact on global public health remains substantial. In recent decades, this has been aggravated due to drug resistance (DR). Administration of the same drugs over the last 40 years, comorbidities such as HIV and type 2 diabetes mellitus, poor drug administration, and inadequate follow-up of the patients are some factors that contribute to the resistance. These aspects have combined so that the twenty-first century has seen the highest number of DR-TB cases in human history. The impact of DR-TB is that failure to address it would jeopardize the Millennium Development Goals for TB promoted by the United Nations (UN) and the world health organization (WHO). The DR-TB requires an integrated approach to reduce its present and future impact. For this reason, two objectives are considered in this chapter; the first one shows the epidemiological and molecular aspects related to DR-TB, and the second one describes the efforts made to develop new drugs and diagnostics. A special emphasis is done on whole-genome sequencing, as the best example of how technologies as diverse as molecular biology, epidemiology, and bioinformatics, can be integrated to solve the DR-TB problem.

Graphical Abstract

General workflow of whole-genome sequencing (WGS) applied to MTBC strains. M-WGS workflow is divided into three principal stages: sample processing (left panel); the second stage (central panel) comprises the process of DNA sequencing; and the last phase includes the bioinformatic analysis (right panel). All these analyses could be achieved separately or following a single pre-designed WGS-pipeline. Importantly, parameters and statistical cut-off must be validated for each step.

*, indicates optional steps; BAL, bronchoalveolar lavage; MGIT, Mycobacterium growth indicator tube; CTAB, cetyltrimethylammonium bromide; DST, drug susceptibility test; SNP, single nucleotide polymorphism; MTBC, Mycobacterium tuberculosis complex.

He who learns but does not think, is lost! He who thinks but does not learn is in great danger.

Confucius

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Acknowledgements

RZ-C was partially funded by “FONDO SECTORIAL DE INVESTIGACIÓN PARA LA EDUCACIÓN CB2017-2018: A1-S-22956.”

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Pérez-Martínez, D. et al. (2023). Drug Resistance in Tuberculosis: Mechanisms, Diagnosis, New Responses, and the Need for an Integrated Approach. In: Rezaei, N. (eds) Tuberculosis. Integrated Science, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-031-15955-8_18

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