Molecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic Fibrosis.

Autor:	Melnik AV; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Vázquez-Baeza Y; Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA.; UC San Diego Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA., Aksenov AA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Hyde E; Department of Pediatrics, University of California, San Diego, La Jolla, California, USA., McAvoy AC; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, USA., Wang M; Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California, USA., da Silva RR; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Protsyuk I; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Wu JV; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Bouslimani A; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Lim YW; Biology Department, San Diego State University, San Diego, California, USA., Luzzatto-Knaan T; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Comstock W; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Quinn RA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Wong R; Department of Pathology, University of California, San Diego, La Jolla, California, USA., Humphrey G; Department of Pediatrics, University of California, San Diego, La Jolla, California, USA., Ackermann G; Department of Pediatrics, University of California, San Diego, La Jolla, California, USA., Spivey T; Department of Radiology, University of California, San Diego, La Jolla, California, USA., Brouha SS; Department of Medicine, University of California, San Diego, La Jolla, California, USA., Bandeira N; Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California, USA., Lin GY; Department of Pathology, University of California, San Diego, La Jolla, California, USA., Rohwer F; Biology Department, San Diego State University, San Diego, California, USA., Conrad DJ; Department of Medicine, University of California, San Diego, La Jolla, California, USA., Alexandrov T; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Knight R; Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.; Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California, USA.; UC San Diego Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA.; Department of Bioengineering, University of California, San Diego, La Jolla, California, USA., Dorrestein PC; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA., Garg N; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA ngarg42@gatech.edu.; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, USA.; Emory-Children's Center for Cystic Fibrosis and Airways Disease Research, Atlanta, Georgia, USA.; Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, USA.
Jazyk:	angličtina
Zdroj:	MSystems [mSystems] 2019 Sep 24; Vol. 4 (5). Date of Electronic Publication: 2019 Sep 24.
DOI:	10.1128/mSystems.00375-19
Abstrakt:	To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella , consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses. IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs. (Copyright © 2019 Melnik et al.)
Databáze:	MEDLINE
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