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EMERGING ISSUES IN MICROBIAL DIVERSITY
SALT LAKE CITY, MAY 2002
WE TEACHMICROBIOLOGY
BUT WE LEARNFROM MICROBES
SOME PERTINENT COMMENTS
"the microbe always has the last word"
"all life in the biosphere depends on microbes"
"all microbiology is environmental
microbiology"
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.
SOME APPLICATIONS
BIOREMEDIATION
FACTORIES
ENZYMES, VECTORS,
PROCESSES (PCR)
DISEASE
BIOTERRORISM
FOOD AND FUEL
DRUGS
EVOLUTION
MICROBES
WHY STUDY?
The Limits of Life
Diversity
Cellular Interactions and Communities
Evolution
Disease
Microbial Physiology
Biotechnology and Bioterrorism
LIMITS OF LIFE
Temperature: 4-130?
pH: 1-10?
Genetic: 20-78% G+C
Pressure
Chemical and physical stress
An example of microbes growing under stress:lichens in an extreme environment.Notre Dame, Paris.
DIVERSITY
Microbial ecology of biological niches
Metagenomes
Unidentified microbial divisions
Small eukaryotes
Unrealised potential
DIRT TO PAYDIRT
DIRT
MICROBES APPLICATIONSIDENTIFICATION
(BIOCATALYSIS,BIOTRANSFORMATION)
(MICROBIAL
CATALOGUE)
DNA rDNA SEQUENCECATALOGUE
METAGENOME
GENES & PATHWAYS
INTERACTIONSSymbiosis
Antagonism
Commensalism
Do all of these responses happen in microbial communities?
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?”
A bacterial mouth!!?(Momma et al. J. Bact. 2000)
HORIZONTAL (LATERAL) GENE TRANSFERHOW CAN IT BE ESTABLISHED?
1. Demonstration in the laboratory or the environment
2. Sequence or motif similarity (DNA or protein)
3. Islands of distinct base composition
4. Nucleic acid hybridisation
5. Association with movable elements
6. Extrachromosomal association
7. Phenotypic and behavioral similarities
Disease
Pathogenesis
Prevention
Treatment and Resistance
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!
Cellular microbiology: the interaction of prokaryotes and eukaryotes
ANTIBIOTIC RESISTANCE MECHANISMS 2001
Decreased influx*Increased efflux*
Enzymatic inactivation*Sequestration*
Target modification*Target by-pass*
Target repairTarget amplification
Biofilm formation? Intracellular localisation
*can be acquired by horizontal gene transfer
From where?
THAT IS THE QUESTION!
Aspects of Antibiotic Resistance
The clinical problem (Medicine)
Why it happened (Human nature)
How it happened (Genetics)
Mechanisms (Biochemistry)
Origins (Speculation)
Solutions (Politics)
HOW BUGS BECOME ANTIBIOTIC RESISTANT:THE PATHWAY TO BECOMING UNTREATABLE
SENSITIVE
MULTIDRUGRESISTANCE
RESISTANCE (low)
M (?)
INC
RE
AS
ING
SE
LE
CT
ION
, ST
RE
SS
, HY
PE
RM
UT
AT
ION
RESISTANCE (medium)(compensation)
M A
(compensation)
RESISTANCE (high)(compensation)
(antagonism)
June 1945:The New York Times
“…..The thoughtlessness of a person playing with penicillin treatment is morally responsible for the death of a man who finally succumbs to infection with the penicillin resistant organism.”
Sir Alexander Fleming
LARGE IS SPECTACULAR, BUT SMALL IS BEAUTIFUL, TOO!
Tantalus Range, B.C.
Genomes, GCs and Small Molecules
Mycoplasma
Chlamydia
Neisseria
Staphylococcus
Mycobacteria
Escherichia
Pseudomonas
Streptomycetes
52
37
66
50
67
75
Genome Size (Mb)
SPECIALISTS
GENERALISTS
84 62
Sec
ond
ary
Met
abol
ite
Pro
du
ctio
n
(%G+C)
42
40
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
Signaling molecule diversity (I)
O
O
H
N
H
OO H
O
O
Br
Br
Br
HN
CH
C
H2 C
O
O
C
OH
O
HNCH
CC
H2
O
O
S
NH
CH
C
CH
OOCH
3
CH2
H3 C
NH
CH
C
CH2
OH
2CS
CH
3
HN
CH
CCH
2O
O
NH
CH
CC
H2
O
O
HO
NH
CH
CC
H
O
O
HO
CH
3
NH
2
CH
CH
2 C
O
O
HO
NH2
CH
C
H2C
O
O
H2C
C
HO
O
HN CH
C
H2C
O
O
CH2
H2C NH
C NH2
HN
HN CH
C
H
O
O HN CH
C
H2C
O
O
CH2
S CH3
HN CH
C
CH
OH
O
HO
CH3
AgrD1 thiolactone signaling peptide from Staphylococcus aureus
Bacillus subtilis CSF (ERGMT)
V. harveyi N-(-hydroxy-butyryl)-L-homoserine lactone
Inhibitory furanone from marine algae Delisea pulchra
OH O
OCH3
3-hydroxypalmitic acid ester from Ralstonia solanacearum
Signaling molecule diversity (II)
O
OH
H
N
OO
O
O
H
N
H
O
N
O
OH
H
N-(3-oxo-dodecanoyl)-L-homoserine lactone (PAI-1)
N-butyryl homoserine lactone (PAI-2)
2-hydroxy-3 heptyl-4-quinolone (PQS)
NH
NH
O
O
HH
H
N
NH
O
O
H
HOH
cyclo (Ala-L-Val) cyclo (L-Pro-L-Tyr)
from Pseudomonas aeruginosa:
Cyclic dipeptides
ANTIBIOTICS
Selection
Induced mutagenesis
Mutagenicity
Transposition
BiofilmsGene delivery
Virulence
Gene transfer
Phage induction
Role of antibiotics in the development of resistance
Biology is much more than
DNA, RNA,
proteins and membranes!
Perlman's rules (1980)
always rightyour frienda sensitive partner
The microorganism is
There are NO stupid microorganisms.
canMicroorganisms 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.
"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
The genealogy of 'omic' sciences(or everyone wants their own "-omic")
GENOMICS
FUNCTIONAL GENOMICS
GNOMICSMETAGENOMICSENTEROMICS VIROMICS
METABOLOMICS PHYSIOMICS
PROTEOMICS
RNOMICS
ARRAYOMICS(TRANSCRIPTOMICS)
ARCHEOMICS
TRANSPOSOMICS
BIOGEOMICS
SYSTOMICS
GLYCOMICS