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bioRxiv · 10.1101/2024.05.27.596016

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

Belheouane, M.·Kalsdorf, B.·Niemann, S.·Gaede, K. I.·Lange, C.·Heyckendorf, J.·Merker, M.
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Abstract

BackgroundPathogenic 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 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 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. ConclusionThe 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.

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Belheouane, M., Kalsdorf, B., Niemann, S., Gaede, K. I., Lange, C., Heyckendorf, J., Merker, M.. 2024-05-27. Serratia sp. dominates the lung microbiome of patients with tuberculosis and non-tuberculous mycobacterial lung diseases. https://doi.org/10.1101/2024.05.27.596016

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