Resistance and Evolving Biology in Mycobacteria: Multidisciplinarity as a Contemporary Approach

Dear Colleagues,

Drug resistance has widely been recognized as a major challenge to effective tuberculosis (TB) control worldwide, and Mycobacterium tuberculosis is considered the leading cause of drug-resistant airborne epidemics globally. Single-nucleotide polymorphisms (SNPs), insertions, and deletions are recognized as the key drivers of M. tuberculosis’ resistance to antituberculosis drugs. The absence of evidence for horizontal gene transfer among TB pathogens has made identifying the genetic foundations of drug resistance somewhat more straightforward; however, the evolutionary complexity of M. tuberculosis, particularly in relation to resistance development, still demands thorough investigation, with a need for attention to be given both to the bacterium itself and its interactions with humans as hosts. Presently, M. tuberculosis strains are classified into seven primary phylogenetic lineages and multiple sublineages, each of which has co-evolved with its host population, resulting in differing propensities for resistance development and, consequently, varied therapeutic outcomes. Despite this, many mutations observed in resistant strains have not yet been conclusively linked to resistance, and numerous resistant strains remain uncharacterized at the molecular genetic level. Even with the availability of potent last-line anti-TB drugs, around half of those infected still succumb to the disease.

The global rise in infections caused by non-tuberculous mycobacteria (NTM), coupled with their increasing resistance to antibiotics—especially anti-TB drugs—poses a significant public health threat. The lack of targeted treatments and the growing difficulty in discovering new antibiotics further exacerbate the challenge. Resistant NTM strains are now infecting not only immunocompromised individuals but also those previously considered healthy. This alarming trend highlights the urgent need for intensified research efforts to develop novel therapeutic strategies and effective drug combinations to combat these resilient pathogens.

In this Special Issue, we will highlight original and review articles that explore the diverse aspects of M. tuberculosis and NTM evolutionary biology in the context of resistance, emphasizing a multidisciplinary research approach. We are looking forward to receiving your papers, and are very grateful to have the opportunity to collaborate with you in this way.

Dr. Irena Arandjelovic
Prof. Dr. Dragana Vukovic
Guest Editors

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• tuberculosis
• drug resistance
• evolutionary biology
• pathogen-host interactions