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

Abstract

AbstractBackgroundPathogenic mycobacteria, such as theMycobacterium tuberculosiscomplex (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 methodsWe 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.ResultsThe generaSerratiaand unclassifiedYersiniaceaedominated 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 (unclassifiedYersiniaceae), and ASV_21 (Serratia) signatures. Exploratory analysis by WMS and ASV similarity analysis suggested the presence ofSerratia liquefaciens,Serratia grimesii,Serratia myotisand/orSerratia quinivoransin both TB and NTM-LD patients. Overall, presence/absence of certainSerratiaASVs was significantly associated with disease state.ConclusionThe lung microbiome of TB patients harbors a distinct, and heterogenous microbiome structure with specific occurrences of certainSerratiatraits.Serratia sp.plays a pivotal role in our understanding of microbial interactions in the lung microbiome of patients infected with Mtbc.