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Biology subjects

Belheouane, M.

Publications and source records attributed to Belheouane, M..

2 recordsLinked to original sources

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

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.

microbiology↗

Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice

Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e. the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally-arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of a AKR/J mouse strain (B6-mtAKR) together with a C57BL/6J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to wild-type C57BL/6J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair metabolic health and lifespan in mice.\n\nHighlightsO_LIWe identify heteroplasmy of the adenine-repeat variation (9 to 13A) in nt5172 in the origin of light-strand DNA replication (OriL) in inbred mice.\nC_LIO_LIB6-mtAKR mice carry >20% 12A heteroplasmy in the OriL, while B6 mice carry only [~] 10% heteroplasmy.\nC_LIO_LIThe level of 12A heteroplasmy correlates to mtDNA copy number, glucose metabolism, and lifespan in mice.\nC_LIO_LIGiven the established role of mtDNA heteroplasmy in regards to endurance exercise performance in athletes, these findings may impact our understanding of metabolism and aging in humans.\nC_LI

genetics↗