Clonal Population of Mycobacterium tuberculosis Strains Reside within Multiple Lung Cavities

Abstract

BackgroundUnsuccessful treatment outcomes among patients with multi-/extensively- drug resistant tuberculosis (TB) have hampered efforts involved in eradicating this disease. In order to better understand the etiology of this disease, we aimed to determine whether single or multiple strains of Mycobacterium tuberculosis (MTB) are localized within lung cavities of patients suffering from chronic progressive TB.Methodology/FindingsMultiple cavity isolates from lung of 5 patients who had undergone pulmonary resection surgery were analyzed on the basis of their drug susceptibility profile, and genotyped by spoligotyping and 24-loci MIRU-VNTR. The patients past history including treatment was studied. Three of the 5 patients had extensive drug resistant TB. Heteroresistance was also reported within different cavity isolates of the lung. Both genotyping methods reported the presence of clonal population of MTB strain within different cavities of the each patient, even those reporting heteroresistance. Four of the 5 patients were infected with a population of the Beijing genotype. Post-surgery they were prescribed a drug regimen consisting of cycloserine, a fluoroquinolone and an injectable drug. A 6 month post-surgery follow-up reported only 2 patients with positive clinical outcome, showing sputum conversion.ConclusionIdentical spoligotype patterns and MIRU-VNTR profiles between multiple cavities of each patient, characterize the presence of clonal population of MTB strains (and absence of multiple MTB infection).

Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment

“…An earlier study investigated different lesions obtained following lung surgery and found discrete pulmonary lesions carried strains with different drug-resistant mutations, which had evolved from a single parental strain 11 . This finding was further confirmed by analyzing the drug susceptibility profile of multiple cavity isolates from 5 patients that underwent pulmonary resection surgery 12 . In these situations, clonal interference does not apply because the strains reside in physically discrete lesions and genetic heteroresistance might therefore be a long-term phenomenon in vivo .…”

Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis

“…The finding of isolates from different lesions in the same patient that have different resistance profiles (ie, heteroresistance), lends support to the hypothesis of differential drug penetration or exposure. 82 Collectively, these data from laboratory experiments, clinical trial simulations, and prospective clinical studies provide support for the notion that biological variability (eg, pharmacokinetic variability) is the main culprit for emergence of multidrug-resistant tuberculosis. Therefore, innovative and new methods are needed to optimally dose patients.…”

Risk factors for pulmonary cavitation in tuberculosis patients from China

“…In MDR cases, the tubercle bacilli are resistant to anti-TB drugs, which results in the chronic progressive disease with cavitation in the lungs of patients. 14 A previous study showed that the presence of pulmonary cavitation is linked to the development of drug resistance during treatment. 28 Therefore, the interaction between pulmonary cavitation and drug resistance may accelerate the generation and expansion of pulmonary cavitation.…”

“…14, 15 A study investigating the relationship between VNTR profiles and disease progression revealed that specific VNTR genotypes were associated with disease progression in Mycobacetrium avium pulmonary infection. 16 Similar results were observed by Shin et al 17 who showed that fibrocavitary diseases were more likely to be grouped into a particular cluster among Mycobacterium abscessus diseases.…”