Persistent Legionnaires' Disease and Associated Antibiotic Treatment Engender a Highly Disturbed Pulmonary Microbiome Enriched in Opportunistic Microorganisms

Ana Elena Pérez-Cobas (1) , Christophe Ginevra (2, 3) , Christophe Rusniok (1) , Sophie Jarraud (2, 3) , Carmen Buchrieser (1)

1 Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria
2 LegioPath - Pathogenèse des légionelles- Legionella pathogenesis
3 CNR - Centre National de Référence des Légionelles

Despite the importance of pneumonia to public health, little is known about the composition of the lung microbiome during infectious diseases, such as pneumonia, and how it evolves during antibiotic therapy. To study the possible relation of the pulmonary microbiome to the severity and outcome of this respiratory disease, we analyzed the dynamics of the pathogen and the human lung micro-biome during persistent infections caused by the bacterium Legionella pneumophila and their evolution during antimicrobial treatment. We collected 10 bronchoalveolar lavage fluid samples from three patients during long-term hospitalization due to pneumonia and performed a unique longitudinal study of the interkingdom micro-biome, analyzing the samples for presence of bacteria, archaea, fungi, and protozoa by high-throughput Illumina sequencing of marker genes. The lung microbiome of the patients was characterized by a strong predominance of the pathogen, a low diversity of the bacterial fraction, and an increased presence of opportunistic microorganisms. The fungal fraction was more stable than the bacterial fraction. During long-term treatment, no genomic changes or antibiotic resistance-associated mutations that could explain the persistent infection occurred, according to whole-genome sequencing analyses of the pathogen. After antibiotic treatment, the micro-biome did not recover rapidly but was mainly constituted of antibiotic-resistant species and enriched in bacteria, archaea, fungi, or protozoa associated with patho-genicity. The lung microbiome seems to contribute to nonresolving Legionella pneumonia , as it is strongly disturbed during infection and enriched in opportunistic and/or antibiotic-resistant bacteria and microorganisms, including fungi, archaea, and protozoa that are often associated with infections.

Mots clés: Legionella pneumophila; antibiotic resistance; pneumonia; pulmonary microbiome

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

Ana Elena Pérez-Cobas, Christophe Ginevra, Christophe Rusniok, Sophie Jarraud, Carmen Buchrieser. Persistent Legionnaires' Disease and Associated Antibiotic Treatment Engender a Highly Disturbed Pulmonary Microbiome Enriched in Opportunistic Microorganisms. mBio, 2020, 11 (3), pp.e00889-20. ⟨10.1128/mBio.00889-20⟩. ⟨pasteur-02860054⟩