Serratia sp. dominates the lung microbiome of patients with tuberculosis and non-tuberculous mycobacterial lung diseases

Background Pathogenic mycobacteria, such as the Mycobacterium tuberculosis complex (Mtbc), and non-tuberculous mycobacteria (NTMs) can cause severe chronic pulmonary infections. However, not all infected patients develop active disease. Yet, it is unclear whether certain key taxa in the lung microbiome play a role in the pathogenesis of tuberculosis (TB) and NTM lung disease (LD). Material and methods We employed 16S rRNA amplicon sequencing (V3-V4) to characterize the baseline microbiome in bronchoalveolar lavage fluid from a patient cohort diagnosed with TB (n=23), NTM-LD (n=19), or non-infectious disease (n=4) prior to the initiation of therapy. The analysis included the depletion of human cells, removal of extracellular DNA, implementation of a decontamination strategy, and exploratory whole-metagenome sequencing (WMS) of selected specimens. Results The genera Serratia and unclassified Yersiniaceae dominated the lung microbiome of all patients with a mean relative abundance of >15% and >70%, respectively. However, at the sub-genus level, as determined by amplicon sequence variants (ASVs), TB-patients exhibited increased community diversity, and TB specific ASV_7 (unclassified Yersiniaceae ), and ASV_21 ( Serratia ) signatures. Exploratory analysis by WMS and ASV similarity analysis suggested the presence of Serratia liquefaciens , Serratia grimesii , Serratia myotis and/or Serratia quinivorans in both TB and NTM-LD patients. Overall, presence/absence of certain Serratia ASVs was significantly associated with disease state. Conclusion The lung microbiome of TB patients harbors a distinct, and heterogenous microbiome structure with specific occurrences of certain Serratia traits. Serratia sp. plays a pivotal role in our understanding of microbial interactions in the lung microbiome of patients infected with Mtbc.