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EMERGING ISSUES IN MICROBIAL DIVERSITY

EMERGING ISSUES IN MICROBIAL DIVERSITY. SALT LAKE CITY, MAY 2002. WE TEACH MICROBIOLOGY. BUT WE LEARN FROM MICROBES. SOME PERTINENT COMMENTS. "the microbe always has the last word" "all life in the biosphere depends on microbes" "all microbiology is environmental microbiology".

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EMERGING ISSUES IN MICROBIAL DIVERSITY

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  1. EMERGING ISSUES IN MICROBIAL DIVERSITY SALT LAKE CITY, MAY 2002 WE TEACH MICROBIOLOGY BUT WE LEARN FROM MICROBES

  2. SOME PERTINENT COMMENTS "the microbe always has the last word" "all life in the biosphere depends on microbes" "all microbiology is environmental microbiology"

  3. THE HIDDEN WORLDS OF MICROBIOLOGY • The number of prokaryote cells in the biosphere (but not the universe?) is estimated to be 6,000,000,000,000,000,000,000,000,000,000 (6 x 1030). • These contain 50% of the earth's carbon, 90% of nitrogen and phosphorus, and more than 108 species. • In our colons, there are about 1012 bacteria, not all of which have been identified. • To date, only 1,500 microbes are known to cause disease in humans or animals. • There are <109 bacteria in 1 gram of soil. • A gram of soil contains 1,000-5,000 different species of bacteria. But what of the eukaryotic microbes? Recent studies show a vast hidden diversity of fungi and protists in the biosphere.

  4. SOME APPLICATIONS FACTORIES DISEASE FOOD AND FUEL MICROBES ENZYMES, VECTORS, PROCESSES (PCR) BIOTERRORISM DRUGS EVOLUTION BIOREMEDIATION

  5. WHY STUDY?The Limits of Life DiversityCellular Interactions and CommunitiesEvolutionDiseaseMicrobial PhysiologyBiotechnology and Bioterrorism

  6. LIMITS OF LIFE Temperature: 4-130? pH: 1-10? Genetic: 20-78% G+C Pressure Chemical and physical stress

  7. An example of microbes growing under stress: lichens in an extreme environment. Notre Dame, Paris.

  8. DIVERSITY Microbial ecology of biological niches Metagenomes Unidentified microbial divisions Small eukaryotes Unrealised potential

  9. DIRT TO PAYDIRT IDENTIFICATION MICROBES APPLICATIONS (MICROBIAL CATALOGUE) (BIOCATALYSIS, BIOTRANSFORMATION) DIRT rDNA SEQUENCE CATALOGUE METAGENOME DNA GENES & PATHWAYS

  10. INTERACTIONS Symbiosis Antagonism Commensalism Do all of these responses happen in microbial communities?

  11. THE ROLES OF MICROBES IN THE EVOLUTION OF HIGHER LIFE FORMS AND THE CONSTANT EVOLUTION OF MICROBES: Morphogenesis Developmental programmes Regulatory networks Pathogenesis “Why worry about life in space (astrobiology, etc.) when terrestrial microbes can provide clues as to the origins and evolution of eukaryotic differentiation?”

  12. A bacterial mouth!!?(Momma et al. J. Bact. 2000)

  13. HORIZONTAL (LATERAL) GENE TRANSFERHOW CAN IT BE ESTABLISHED? Demonstration in the laboratory or the environment Sequence or motif similarity (DNA or protein) Islands of distinct base composition Nucleic acid hybridisation Association with movable elements Extrachromosomal association Phenotypic and behavioral similarities

  14. Disease Pathogenesis Prevention Treatment and Resistance

  15. Know the enemy • Life cycle and ecology of infectious microbes • Evolutionary lineage • Environmental changes associated with infection • Host-range variation • Diagnosis • Mechanisms of host/pathogen interaction • Mechanisms of resistance • Host susceptibility determinants • CELLULAR MICROBIOLOGY!

  16. Cellular microbiology: the interaction of prokaryotes and eukaryotes

  17. ANTIBIOTIC RESISTANCE MECHANISMS 2001 • Decreased influx* • Increased efflux* • Enzymatic inactivation* • Sequestration* • Target modification* • Target by-pass* • Target repair • Target amplification • Biofilm formation • ? Intracellular localisation • *can be acquired by horizontal gene transfer • From where? • THAT IS THE QUESTION!

  18. Aspects of Antibiotic Resistance The clinical problem (Medicine) Why it happened (Human nature) How it happened (Genetics) Mechanisms (Biochemistry) Origins (Speculation) Solutions (Politics)

  19. M (?) RESISTANCE (low) M A INCREASING SELECTION, STRESS, HYPERMUTATION (compensation) RESISTANCE (medium) (compensation) RESISTANCE (high) MULTIDRUG (compensation) (antagonism) RESISTANCE HOW BUGS BECOME ANTIBIOTIC RESISTANT: THE PATHWAY TO BECOMING UNTREATABLE SENSITIVE

  20. Tantalus Range, B.C. LARGE IS SPECTACULAR, BUT SMALL IS BEAUTIFUL, TOO!

  21. Genomes, GCs and Small Molecules 75 Streptomycetes 67 Pseudomonas 50 Escherichia 66 GENERALISTS Mycobacteria Secondary Metabolite Production SPECIALISTS 37 Staphylococcus 52 Neisseria 42 Chlamydia 40 4 6 8 2 Mycoplasma Genome Size (Mb) (%G+C)

  22. MULTIPLE ACTIVITIES FOR SMALL MOLECULES IN BIOLOGY Growth inhibitors, allosteric effectors,transcription activators, pheromones,quorum sensors, insecticides, immunosuppressives, cell-signalling, hormone analogs, plant growth regulators, surfactants, antivirals, antitumour agents, herbicides, antiparasitics, antihelminthics, antifungals, cholesterol-lowering agents, and enzyme inhibitors

  23. B r H O O H O B r B r O H O N H 2 H H C C H 2 O C H O 3 O C O N O O N H O H O C C H O C H 2 O N H H O O C C H O H C O O C H C H H N 3 H H C O 2 C N C H H O C H O C H 2 C S O O C H 2 H N C S C H C C H H C 2 C H N H 3 H 2 C O O O C N C H H O C H H C 3 C H 3 C H 2 H O C O H N O H C N H C N H C O H 2 2 2 H C C H H C N H O H N C H 2 2 C O H C C H C O C H C H 2 2 3 O H N C H O H N C H H O C O C O H C C H 2 2 O H N C H S C H 3 H Signaling molecule diversity (I) V. harveyiN-(b-hydroxy-butyryl)-L-homoserine lactone 3-hydroxypalmitic acid ester from Ralstonia solanacearum Inhibitory furanone from marine algae Delisea pulchra AgrD1 thiolactone signaling peptide from Staphylococcus aureus Bacillus subtilis CSF (ERGMT)

  24. H H H O N O N H N H O N H O H O H H O O H O N H O O O H O H O N H O N H Signaling molecule diversity (II) from Pseudomonas aeruginosa: N-butyryl homoserine lactone (PAI-2) N-(3-oxo-dodecanoyl)-L-homoserine lactone (PAI-1) 2-hydroxy-3 heptyl-4-quinolone (PQS) cyclo (D Ala-L-Val) cyclo (L-Pro-L-Tyr) Cyclic dipeptides

  25. Role of antibiotics in the development of resistance Selection Phage induction Induced mutagenesis Mutagenicity Virulence ANTIBIOTICS Gene transfer Transposition Gene delivery Biofilms

  26. Biology is much more thanDNA, RNA,proteins and membranes!

  27. Perlman's rules (1980) always right your friend a sensitive partner The microorganism is There are NO stupid microorganisms. can Microorganisms do anything. will smarter than chemists, Microorganisms are wiser than engineers, more energetic than etc. If you take care of your microbial friends, they will take care of your future and you will live happily ever after.

  28. "It is essential that microbiology be perceived and practiced in a way consistent with the natural order of things; microbes are the base for and sustain all other life on this planet. Let us reorganize all of biology around microbiology." Carl R. Woese 1994

  29. The genealogy of 'omic' sciences(or everyone wants their own "-omic") GENOMICS ENTEROMICS VIROMICS METAGENOMICS GNOMICS ARCHEOMICS BIOGEOMICS FUNCTIONAL GENOMICS PROTEOMICS GLYCOMICS METABOLOMICS PHYSIOMICS ARRAYOMICS (TRANSCRIPTOMICS) SYSTOMICS TRANSPOSOMICS RNOMICS

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