Editorial: Non-tuberculous mycobacteria and bronchiectasis

The epidemiological significance of nontuberculous mycobacterial (NTM) diseases was not recognized until the early 1950s, many decades after Koch announced the discovery of Mycobacterium tuberculosis in 1882. It was not until the mid-1980s that clinicians described the non-classic, nodular-bronchiectatic form of NTM pulmonary infection, distinguishing it from the previously recognized classic, cavitary presentation. By the late 1980s, bronchiectasis itself was still regarded as an orphan disease. Since then, the field has rapidly evolved into one of the fastest-growing areas of interest in respiratory medicine, yet research in NTM infections continues to lag markedly behind that devoted to tuberculosis. This editorial examines the contributions included on the topic "Nontuberculous mycobacteria and bronchiectasis." This collection includes one review that explores the cause-and-effect relationship between the two conditions [1], along with four original research articles. One study examines the epidemiology of the infection and concludes that the available evidence does not support person-to-person transmission of the disease [2]. The next article investigates an infection caused by the uncommon species Mycobacterium colombiense, which led to the development of bronchiectasis [3]. The third article analyzes the differences in granuloma formation induced by M. tuberculosis and M. avium [4]. The final one describes a murine model that replicates key features of cystic fibrosis, a condition closely associated with the development of bronchiectasis [5].Rubio et al. [2] investigated pathogen transmission by analyzing the cluster structure of 46 M. avium complex isolates obtained from patients with bronchiectasis, using whole-genome sequencing. Bronchiectasis provides a favorable environment for mycobacterial proliferation and facilitates their expulsion from the lungs through coughing. The researchers identified two clusters, each composed of two strains from different patients, isolated more than a year apart and without any evident epidemiological link, prompting the conclusion that person-to-person transmission had not occurred. If these strains share a common ancestor, the mode of transmission remains unresolved and is likely to involve indirect routes such as fomites-an area currently under active investigation. This study also offers valuable insights into the genomic diversity of M. intracellulare and M. avium species.Among the species most frequently isolated today are M. avium, M. intracellulareinvestigated by Rubio et al. [2]-and M. abscessus. New NTM species, however, continue to be identified in clinical settings. An interesting example is the case reported by Tan et al. [ integrity. This more stable granuloma structure may help shield the mycobacteria, promoting 63 their persistence and the progression to chronic disease, a process in which radiologic findings 64 may evolve from isolated nodules to established bronchiectasis [7]. The evidence generated in 65 this study may help advance ongoing efforts to understand the differing pathogenic 66 mechanisms of the M. tuberculosis complex and NTM. 67The genetic disease most strongly associated to bronchiectasis is cystic fibrosis caused by 68 mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR), a 69 chlorine/bicarbonate channel that balances fluid homeostasis in epithelia. In the airways, 70 mucus becomes dehydrated and mucociliary clearance is severely impaired, creating 71 conditions that facilitate infection by a variety of microorganisms, including mycobacteria. A 72 cystic fibrosis-like phenotype is reproduced in the mice by mutating the βENaC channel, which 73 enhances Na⁺ transport [8]. Given that nearly all patients with cystic fibrosis eventually 74 develop bronchiectasis, this model was used by Pearce et al. to examine the role of M. 75 abscessus, a NTM species frequently isolated in this population [5]. The results showed that 76 the mice were able to clear the mycobacteria, leading to the conclusion that this model is not 77 suitable for studying chronic infection. Nevertheless, a decline in lung function was observed, 78 suggesting that the model may still be useful for investigating the early stages of 79 bronchiectasis development-a possibility that warrants further study. 80The review by Singh et al. [1] may serve as a compendium of the subject matter covered in this 81Research Topic. The authors describe the vicious cycle that arises between NTM infection and 82 bronchiectasis. NTM infection fuels persistent inflammation and tissue damage through 83 cytokine release and granulomatous responses, leading to further architectural distortion of 84 the airways and progression of bronchiectasis. In turn, the structural abnormalities and 85 impaired mucociliary clearance characteristic of bronchiectasis increase susceptibility to NTM 86 acquisition, perpetuating the cycle. The authors also emphasize other key aspects of the 87 disease, such as the diagnostic challenges faced in high-burden countries, where smear 88 microscopy cannot distinguish M. tuberculosis from NTM, making molecular methods 89 essential, as well as the difficulty of differentiating true infection from mere colonization. 90According to international guidelines, confirmation NTM pulmonary disease requires a 91 combination of clinical symptoms, radiological abnormalities, and microbiological evidence, 92 including at least two positive sputum cultures or one positive bronchoscopy sample. The 93 importance of biofilm formation is also stressed, as it promotes microbial persistence and 94 facilitates horizontal gene transfer, thereby potentially increasing antimicrobial resistance and 95 complicating treatment. 96The association between NTM infection and bronchiectasis affects an ever-growing number of 98patients, yet many aspects of their interplay remain poorly understood. The simultaneous rise 99 in the incidence of both conditions is unlikely to be coincidental and may instead reflect a close 100 and biologically meaningful connection. Moreover, the proportion of infections that progress 101 to bronchiectasis and the proportion of pre-existing structural airway abnormalities that 102 predispose to infection are unlikely to be equivalent. In each scenario, the therapeutic 103 priorities would differ, creating opportunities for more tailored and personalized treatment 104 strategies. 105