Microbial Stress: Spaceflight-induced Alterations in Microbial Virulence and Infectious Disease Risks for the Crew

The response of microorganisms to the spaceflight environment has tremendous implications for the risk of infectious disease for astronauts. Seminal studies using Salmonella enterica serovar Typhimurium demonstrated that the organism’s virulence was altered in response to culture in either spaceflight or spaceflight analogue environments. Furthermore, evaluation of global changes in transcriptomic and proteomic profiles in S. Typhimurium in response to culture in these environments indicated that many of the alterations in gene expression were regulated by the conserved chaperone protein, Hfq. To determine similarities in spaceflight and/or spaceflight analogue-induced responses in other pathogens, extensive studies were performed using the opportunistic pathogen Pseudomonas aeruginosa. As with S. Typhimurium, P. aeruginosa cultured in either spaceflight or spaceflight analogue conditions demonstrated diverse molecular genetic response profiles, including those associated with pathogenesis-related responses and the Hfq regulon. Collectively, these discoveries are providing novel insight into both the conserved and varied molecular genetic and phenotypic responses found in a wide variety of pathogens cultured in both spaceflight and spaceflight analogue conditions. Interestingly, the low fluid-shear culture conditions of both spaceflight and spaceflight analogue environments are relevant to those encountered by pathogens in certain regions of the human body during the natural course of infection. Hence, novel virulence strategies unveiled during spaceflight and spaceflight analogue culture hold promise to safeguard crew health, and may aid the quest for novel therapeutics and vaccines against pathogens for the general public on Earth.

[1]  Patrick De Boever,et al.  Use of the rotating wall vessel technology to study the effect of shear stress on growth behaviour of Pseudomonas aeruginosa PA01. , 2008, Environmental microbiology.

[2]  J. Vogel,et al.  Deep Sequencing Analysis of Small Noncoding RNA and mRNA Targets of the Global Post-Transcriptional Regulator, Hfq , 2008, PLoS genetics.

[3]  Jonathan S. Dordick,et al.  Spaceflight Promotes Biofilm Formation by Pseudomonas aeruginosa , 2013, PloS one.

[4]  Raju Tomer,et al.  A small non‐coding RNA of the invasion gene island (SPI‐1) represses outer membrane protein synthesis from the Salmonella core genome , 2007, Molecular microbiology.

[5]  D. Pierson,et al.  Low-Shear Modeled Microgravity Alters the Salmonella enterica Serovar Typhimurium Stress Response in an RpoS-Independent Manner , 2002, Applied and Environmental Microbiology.

[6]  K J Dickson Summary of biological spaceflight experiments with cells. , 1991, ASGSB bulletin : publication of the American Society for Gravitational and Space Biology.

[7]  Mark C. Ott,et al.  Human Immune Function and Microbial Pathogenesis in Human Spaceflight , 2006 .

[8]  Eoin L. Brodie,et al.  Role and Regulation of σs in General Resistance Conferred by Low-Shear Simulated Microgravity in Escherichia coli , 2004, Journal of bacteriology.

[9]  D. Pierson,et al.  Characterization of Escherichia coli MG1655 grown in a low-shear modeled microgravity environment , 2007, BMC Microbiology.

[10]  Duane L. Pierson,et al.  Microbial Surveillance of Potable Water Sources of the International Space Station , 2005 .

[11]  J. Ghigo,et al.  Escherichia coli biofilms. , 2008, Current topics in microbiology and immunology.

[12]  P. Ayyaswamy,et al.  Escherichia coli Biofilms Formed under Low-Shear Modeled Microgravity in a Ground-Based System , 2006, Applied and Environmental Microbiology.

[13]  B. Gunn,et al.  Salmonella enterica Serovar Typhimurium Strains with Regulated Delayed Attenuation In Vivo , 2008, Infection and Immunity.

[14]  D. Pierson,et al.  Microbial Characterization during the Early Habitation of the International Space Station , 2004, Microbial Ecology.

[15]  G. Storz,et al.  Bacterial stress responses. , 2011 .

[16]  S. Gottesman The small RNA regulators of Escherichia coli: roles and mechanisms*. , 2004, Annual review of microbiology.

[17]  T. Tolker-Nielsen,et al.  Multiple Roles of Biosurfactants in Structural Biofilm Development by Pseudomonas aeruginosa , 2007, Journal of bacteriology.

[18]  N. Majdalani,et al.  Small RNA regulators and the bacterial response to stress. , 2006, Cold Spring Harbor symposia on quantitative biology.

[19]  Matthew R. Parsek,et al.  Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms , 2000, Nature.

[20]  M. Kacena,et al.  Gentamicin: effect on E. coli in space. , 1999, Microgravity science and technology.

[21]  Jennifer Barrila,et al.  DISCOVERY OF SPACEFLIGHT-RELATED VIRULENCE MECHANISMS IN SALMONELLA AND OTHER MICROBIAL PATHOGENS: NOVEL APPROACHES TO COMMERCIAL VACCINE DEVELOPMENT , 2011 .

[22]  J. W. Wilson,et al.  Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq , 2007, Proceedings of the National Academy of Sciences.

[23]  Cécile Huin-Schohn,et al.  Could spaceflight‐associated immune system weakening preclude the expansion of human presence beyond Earth's orbit? , 2009, Journal of leukocyte biology.

[24]  P. Volz,et al.  Phosphate uptake in Saccharomyces cerevisiae Hansen wild type and phenotypes exposed to space flight irradiation , 1979, Applied and environmental microbiology.

[25]  J. Hinds,et al.  Low-shear modelled microgravity alters expression of virulence determinants of Staphylococcus aureus , 2010 .

[26]  G R Taylor,et al.  Recovery of medically important microorganisms from Apollo astronauts. , 1974, Aerospace medicine.

[27]  David M Klaus,et al.  Antibiotic efficacy and microbial virulence during space flight. , 2006, Trends in biotechnology.

[28]  Kelly Johanson,et al.  Saccharomyces cerevisiae gene expression changes during rotating wall vessel suspension culture. , 2002, Journal of applied physiology.

[29]  C. M. Ott,et al.  Induction of Attachment-Independent Biofilm Formation and Repression of hfq Expression by Low-Fluid-Shear Culture of Staphylococcus aureus , 2011, Applied and Environmental Microbiology.

[30]  L. Teel,et al.  A three‐dimensional tissue culture model for the study of attach and efface lesion formation by enteropathogenic and enterohaemorrhagic Escherichia coli , 2005, Cellular microbiology.

[31]  D. Learn,et al.  Hypochlorite scavenging by Pseudomonas aeruginosa alginate , 1987, Infection and immunity.

[32]  G Richoilley,et al.  Study of minimal inhibitory concentration of antibiotics on bacteria cultivated in vitro in space (Cytos 2 experiment). , 1985, Aviation, space, and environmental medicine.

[33]  N. Høiby,et al.  Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients , 2009, Pediatric pulmonology.

[34]  Diane O. Inglis,et al.  Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans , 2013, PloS one.

[35]  Sara D. Altenburg,et al.  Increased Filamentous Growth of Candida albicans in Simulated Microgravity , 2008, Genom. Proteom. Bioinform..

[36]  C. Mark Ott,et al.  Transcriptional and Proteomic Responses of Pseudomonas aeruginosa PAO1 to Spaceflight Conditions Involve Hfq Regulation and Reveal a Role for Oxygen , 2010, Applied and Environmental Microbiology.

[37]  B. Iglewski,et al.  P. aeruginosa Biofilms in CF Infection , 2008, Clinical reviews in allergy & immunology.

[38]  David W. Niesel,et al.  Transcription profiles of Streptococcus pneumoniae grown under different conditions of normal gravitation , 2007 .

[39]  A. Demain,et al.  Shear stress enhances microcin B17 production in a rotating wall bioreactor, but ethanol stress does not , 2001, Applied Microbiology and Biotechnology.

[40]  B. Gunn,et al.  New technologies in using recombinant attenuated Salmonella vaccine vectors. , 2010, Critical reviews in immunology.

[41]  H. Schellhorn,et al.  Role of RpoS in Virulence of Pathogens , 2009, Infection and Immunity.

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

[43]  P. Volz Mycology studies in space , 1990, Mycopathologia.

[44]  M. Plotkowski,et al.  Cytotoxicity of Pseudomonas aeruginosa internal lectin PA-I to respiratory epithelial cells in primary culture , 1994, Infection and immunity.

[45]  Satish K. Mehta,et al.  CHAPTER 40 – Reactivation of Latent Herpes Viruses in Astronauts , 2007 .

[46]  N. Schiller,et al.  Inhibition of Macrophage Phagocytosis by Pseudomonas aeruginosa Rhamnolipids In Vitro and In Vivo , 1996, Current Microbiology.

[47]  L. Mizrahi,et al.  Mannose-binding hemagglutinins in extracts of Pseudomonas aeruginosa. , 1977, Canadian Journal of Biochemistry.

[48]  Wei Sun,et al.  Live Recombinant Salmonella Typhi Vaccines Constructed to Investigate the Role of rpoS in Eliciting Immunity to a Heterologous Antigen , 2010, PloS one.

[49]  J. Blake A note on mucus shear rates. , 1973, Respiration physiology.

[50]  N. Majdalani,et al.  Bacterial Small RNA Regulators , 2005, Critical reviews in biochemistry and molecular biology.

[51]  C. Mark Ott,et al.  Media Ion Composition Controls Regulatory and Virulence Response of Salmonella in Spaceflight , 2008, PloS one.

[52]  J. Sha,et al.  Alterations in the Virulence Potential of Enteric Pathogens and Bacterial–Host Cell Interactions Under Simulated Microgravity Conditions , 2006, Journal of toxicology and environmental health. Part A.

[53]  R. McLean,et al.  Bacterial biofilm formation under microgravity conditions. , 2001, FEMS microbiology letters.

[54]  W. R. Hawkins,et al.  Clinical aspects of crew health , 1975 .

[55]  L. Hyman,et al.  Effects of Low-Shear Modeled Microgravity on Cell Function, Gene Expression, and Phenotype in Saccharomyces cerevisiae , 2006, Applied and Environmental Microbiology.

[56]  A. Imberty,et al.  Role of LecA and LecB Lectins in Pseudomonas aeruginosa-Induced Lung Injury and Effect of Carbohydrate Ligands , 2009, Infection and Immunity.

[57]  G. O’Toole,et al.  Rhamnolipid Surfactant Production Affects Biofilm Architecture in Pseudomonas aeruginosa PAO1 , 2003, Journal of bacteriology.

[58]  G. Weinstock,et al.  Epidemiology of Staphylococcus aureus during space flight. , 1996, FEMS immunology and medical microbiology.

[59]  D. Pierson,et al.  Microbial Responses to Microgravity and Other Low-Shear Environments , 2004, Microbiology and Molecular Biology Reviews.

[60]  G. Rotilio,et al.  Low-Shear Modeled Microgravity Enhances Salmonella Enterica Resistance to Hydrogen Peroxide Through a Mechanism Involving KatG and KatN , 2012, The open microbiology journal.

[61]  G. Pier,et al.  Role of Alginate O Acetylation in Resistance of Mucoid Pseudomonas aeruginosa to Opsonic Phagocytosis , 2001, Infection and Immunity.

[62]  B. Gunn,et al.  Evaluation of new generation Salmonella enterica serovar Typhimurium vaccines with regulated delayed attenuation to induce immune responses against PspA , 2009, Proceedings of the National Academy of Sciences.

[63]  P. Monsieurs,et al.  Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation. , 2010, Environmental microbiology.

[64]  C. Gross,et al.  Hfq Modulates the σE-Mediated Envelope Stress Response and the σ32-Mediated Cytoplasmic Stress Response in Escherichia coli , 2006 .

[65]  Sara D. Altenburg,et al.  Yeast genomic expression patterns in response to low-shear modeled microgravity , 2007, BMC Genomics.

[66]  Jasmine Shong,et al.  Effect of spaceflight on Pseudomonas aeruginosa final cell density is modulated by nutrient and oxygen availability , 2013, BMC Microbiology.

[67]  A. Torres,et al.  The effects of low-shear stress on Adherent-invasive Escherichia coli. , 2008, Environmental microbiology.

[68]  J. Vogel,et al.  The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium , 2007, Molecular microbiology.

[69]  C. Mark Ott,et al.  Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[70]  J. Costerton,et al.  Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis , 1980, Infection and immunity.

[71]  D M Klaus,et al.  Clinostats and bioreactors. , 2007, Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology.

[72]  M. Juergensmeyer,et al.  Long-term exposure to spaceflight conditions affects bacterial response to antibiotics. , 1999, Microgravity science and technology.

[73]  B. Gunn,et al.  Immunogenicity of a Live Recombinant Salmonellaenterica Serovar Typhimurium Vaccine Expressing pspA in Neonates and Infant Mice Born from Naïve and Immunized Mothers , 2010, Clinical and Vaccine Immunology.

[74]  C. Mark Ott,et al.  Microgravity as a Novel Environmental Signal Affecting Salmonella enterica Serovar Typhimurium Virulence , 2000, Infection and Immunity.

[75]  D. Pierson,et al.  Novel Quantitative Biosystem for Modeling Physiological Fluid Shear Stress on Cells , 2006, Applied and Environmental Microbiology.

[76]  Lawrence F. Dietlein,et al.  Biomedical Results of Apollo , 2011 .