Abstract

In this study, our aims were to comparatively analyze the power of variable number tandem repeat (VNTR) typing to discriminate isolates within subspecies and to identify a potential genetic marker for better molecular typing of Mycobacterium abscessus complex (MABC) strains. A total of 103 clinical MABC isolates were collected from a nationwide cross-sectional study in China. Eighteen VNTR loci were chosen to genotype the MABC isolates. Of the 103 clinical MABC isolates, there were 76 (73.8%) M. abscessus subsp. abscessus (MAA) and 27 (26.2%) M. abscessus subsp. massiliense (MAM) isolates. Among the patients with MAA lung diseases, the percentage of patients older than 45 years (67.1%) was significantly higher than that of patients with MAM lung diseases [33.3%, adjusted odds ratio (aOR) = 0.36, 95% CI = 0.13–0.98, p = 0.046]. Fifteen VNTR loci were designated as being “highly discriminant” in our sample, except for TR109. The total of 103 MABC isolates were fully discriminated into 103 unique patterns by an 18-locus VNTR set [Hunter–Gaston Discriminatory Index (HGDI) = 1.000], of which the inclusion of the top 12 loci yielded a comparative HGDI value (HGDI = 0.9998). Remarkably, the order of the diversity of the VNTR loci showed significant difference between the MAA and MAM isolates. TR137 and TR2, two loci with high diversity indices for the MAA isolates, only yielded poor discriminatory power for the MAM isolates; the allelic diversity (h) values were 0.0000 and 0.2621, respectively. A detailed analysis of TR137 in combination with the other 17 VNTR loci showed that the combination of TR137–TR2 could fully distinguish MAA from MAM isolates. In conclusion, our data revealed that MAA is more prone to affect elderly patients. Additionally, the population structure of the MABC isolates circulating in China has high diversity. The combined use of the TR137 and TR2 loci provides a simple criterion for the precise identification of MABC to the subspecies level.

Highlights

  • Worldwide, infections due to non-tuberculous mycobacteria (NTM) appear to be increasing (Thomson and NTM working group at Queensland TB Control Centre and Queensland Mycobacterial Reference Laboratory, 2010; Pang et al, 2017)

  • Among the patients with M. abscessus subsp. abscessus (MAA) lung diseases, the percentage of patients older than 45 years (67.1%) was significantly higher than that of patients with M. abscessus subsp. massiliense (MAM) lung diseases [33.3%, adjusted odds ratio = 0.36 95% CI = 0.13–0.98, p = 0.046]

  • Our data demonstrate that the Mycobacterium abscessus complex (MABC) isolates causing pulmonary diseases primarily originate from the environmental niche

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Summary

Introduction

Infections due to non-tuberculous mycobacteria (NTM) appear to be increasing (Thomson and NTM working group at Queensland TB Control Centre and Queensland Mycobacterial Reference Laboratory, 2010; Pang et al, 2017). MABC is composed of the most common rapid growing mycobacteria that cause human diseases, accounting for 23.1% of pulmonary infections due to NTM in China (Tan et al, 2021). MAM has a truncated erm(41) gene, whereas MAA has a functional erm(41) gene corresponding to inducible resistance, thereby leading to poorer outcomes (Choi et al, 2012). This sequence divergence indicates significant evolutionary differences between these two neighboring mycobacteria. Further comparative investigation of their genetic diversity will extend our knowledge of these microorganisms

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