Niche partitioning of a pathogenic microbiome driven by chemical gradients

Chemical gradients shape the cystic fibrosis lung microbiome, with marked effects on the outcome of antimicrobial treatments. Environmental microbial communities are stratified by chemical gradients that shape the structure and function of these systems. Similar chemical gradients exist in the human body, but how they influence these microbial systems is more poorly understood. Understanding these effects can be particularly important for dysbiotic shifts in microbiome structure that are often associated with disease. We show that pH and oxygen strongly partition the microbial community from a diseased human lung into two mutually exclusive communities of pathogens and anaerobes. Antimicrobial treatment disrupted this chemical partitioning, causing complex death, survival, and resistance outcomes that were highly dependent on the individual microorganism and on community stratification. These effects were mathematically modeled, enabling a predictive understanding of this complex polymicrobial system. Harnessing the power of these chemical gradients could be a drug-free method of shaping microbial communities in the human body from undesirable dysbiotic states.

[1]  M. Welsh,et al.  Reduced Airway Surface pH Impairs Bacterial Killing in the Porcine Cystic Fibrosis Lung , 2012, Nature.

[2]  R. Hunter,et al.  Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease , 2016, bioRxiv.

[3]  Barbara A. Bailey,et al.  Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome , 2015, The ISME Journal.

[4]  D. Newman,et al.  Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation , 2015, mBio.

[5]  S. Lynch,et al.  The cystic fibrosis airway microbiome. , 2013, Cold Spring Harbor perspectives in medicine.

[6]  Richard C Boucher,et al.  Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. , 2002, The Journal of clinical investigation.

[7]  J. Clancy,et al.  Nasal potential difference measurements to assess CFTR ion channel activity. , 2011, Methods in molecular biology.

[8]  M. Kühl,et al.  Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum , 2014, Front. Microbiol..

[9]  M. Sánchez Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia , 2015, Front. Microbiol..

[10]  P. Tulkens,et al.  Aminoglycosides: Activity and Resistance , 1999, Antimicrobial Agents and Chemotherapy.

[11]  Kristian Fog Nielsen,et al.  Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking , 2016, Nature Biotechnology.

[12]  Jose A Navas-Molina,et al.  Balance Trees Reveal Microbial Niche Differentiation , 2017, mSystems.

[13]  U. Römling,et al.  Microcolony formation: a novel biofilm model of Pseudomonas aeruginosa for the cystic fibrosis lung. , 2005, Journal of medical microbiology.

[14]  L. Hoffman,et al.  Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset , 2011, Expert review of molecular diagnostics.

[15]  Jose A Navas-Molina,et al.  Deblur Rapidly Resolves Single-Nucleotide Community Sequence Patterns , 2017, mSystems.

[16]  Shibu Yooseph,et al.  Meta-omics uncover temporal regulation of pathways across oral microbiome genera during in vitro sugar metabolism , 2015, The ISME Journal.

[17]  Nuno Bandeira,et al.  Interkingdom metabolic transformations captured by microbial imaging mass spectrometry , 2012, Proceedings of the National Academy of Sciences.

[18]  Barbara A. Bailey,et al.  A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation , 2015, The ISME Journal.

[19]  Daniel G. Lee,et al.  Pyocyanin Production by Pseudomonas aeruginosa Induces Neutrophil Apoptosis and Impairs Neutrophil-Mediated Host Defenses In Vivo1 , 2005, The Journal of Immunology.

[20]  T. Fenchel,et al.  Oxygen and the Spatial Structure of Microbial Communities , 2008, Biological reviews of the Cambridge Philosophical Society.

[21]  Robert Schmieder,et al.  Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2,3-butanedione fermentation , 2014, The ISME Journal.

[22]  Nigel W. Hardy,et al.  Proposed minimum reporting standards for chemical analysis , 2007, Metabolomics.

[23]  Matej Oresic,et al.  MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data , 2010, BMC Bioinformatics.

[24]  Sophie J. Weiss,et al.  Correlation detection strategies in microbial data sets vary widely in sensitivity and precision , 2016, The ISME Journal.

[25]  F. Rohwer,et al.  Ecological networking of cystic fibrosis lung infections , 2016, npj Biofilms and Microbiomes.

[26]  P. Salamon,et al.  Cystic fibrosis therapy: a community ecology perspective. , 2013, American journal of respiratory cell and molecular biology.

[27]  L. Rigottier-Gois,et al.  Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis , 2013, The ISME Journal.

[28]  A. Warris,et al.  Aspergillus infections in cystic fibrosis. , 2016, The Journal of infection.

[29]  S. Doucette,et al.  Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis , 2011, Thorax.

[30]  K. Kerr,et al.  Survival of Stenotrophomonas maltophilia following exposure to concentrations of tobramycin used in aerosolized therapy for cystic fibrosis patients. , 2001, International journal of antimicrobial agents.

[31]  D. Jahn,et al.  Anaerobic physiology of Pseudomonas aeruginosa in the cystic fibrosis lung. , 2010, International journal of medical microbiology : IJMM.

[32]  M. Whiteley,et al.  Oxygen levels rapidly modulate Pseudomonas aeruginosa social behaviours via substrate limitation of PqsH , 2010, Molecular microbiology.

[33]  Theodore Alexandrov,et al.  3D molecular cartography using LC–MS facilitated by Optimus and 'ili software , 2017, Nature Protocols.

[34]  R. Knight,et al.  Pyrosequencing-Based Assessment of Soil pH as a Predictor of Soil Bacterial Community Structure at the Continental Scale , 2009, Applied and Environmental Microbiology.

[35]  W. Blankenfeldt,et al.  Recent insights into the diversity, frequency and ecological roles of phenazines in fluorescent Pseudomonas spp. , 2013, Environmental microbiology.

[36]  S. Garneau‐Tsodikova,et al.  Cosubstrate Tolerance of the Aminoglycoside Resistance Enzyme Eis from Mycobacterium tuberculosis , 2012, Antimicrobial Agents and Chemotherapy.

[37]  J. Lipuma,et al.  Cystic fibrosis lung microbiome: Opportunities to reconsider management of airway infection , 2015, Pediatric pulmonology.

[38]  Barbara A. Bailey,et al.  Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease , 2014, The ISME Journal.

[39]  J. Bargon,et al.  Prophylactic antibiotic therapy is associated with an increased prevalence of Aspergillus colonization in adult cystic fibrosis patients. , 1999, Respiratory medicine.

[40]  M. Elkins,et al.  Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolates Derived from Patients with Cystic Fibrosis under Aerobic, Anaerobic, and Biofilm Conditions , 2005, Journal of Clinical Microbiology.

[41]  Forest Rohwer,et al.  Biogeochemical Forces Shape the Composition and Physiology of Polymicrobial Communities in the Cystic Fibrosis Lung , 2014, mBio.

[42]  M. Rogers,et al.  Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis , 2018, PloS one.

[43]  Nuno Bandeira,et al.  Three-Dimensional Microbiome and Metabolome Cartography of a Diseased Human Lung. , 2017, Cell host & microbe.

[44]  P. Meda,et al.  Rhamnolipids Are Virulence Factors That Promote Early Infiltration of Primary Human Airway Epithelia by Pseudomonas aeruginosa , 2006, Infection and Immunity.

[45]  M. Dworkin Sergei Winogradsky: a founder of modern microbiology and the first microbial ecologist. , 2012, FEMS microbiology reviews.

[46]  P. Ralph,et al.  A split flow chamber with artificial sediment to examine the below-ground microenvironment of aquatic macrophytes , 2014 .

[47]  J. Rello,et al.  Pseudomonas aeruginosa virulence and therapy: Evolving translational strategies* , 2009, Critical care medicine.

[48]  P. Dorrestein,et al.  The WinCF Model - An Inexpensive and Tractable Microcosm of a Mucus Plugged Bronchiole to Study the Microbiology of Lung Infections. , 2017, Journal of visualized experiments : JoVE.

[49]  Pradeep K. Singh,et al.  Cystic Fibrosis Sputum Supports Growth and Cues Key Aspects of Pseudomonas aeruginosa Physiology , 2005, Journal of bacteriology.