Transcript Evolution and Ecology of Pathogens

Evolution and
Ecology of
Pathogens
Martin Polz
Civil & Environmental Engineering
Massachusetts Institute of Technology
Outline
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Emergence of pathogens
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Re-emergence of pathogens
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Global importance of microorganisms
What are pathogens?
Evolution of pathogenesis
Antibiotic resistance
Cholera
Conclusions
Candice's Germ Poem
Germs, germs everywhere
Even on a little pear,
Germs germs all around,
Even on the dirty ground.
Germs, germs make me sick,
Especially on a candy stick.
Germs, germs are so small,
Even on a bouncy ball.
Microbial communities drive biogeochemical cycles…
Example: The Nitrogen Cycle
<3
fixation in
lightening
100
human activities
ATMOSPHERE
200
denitrification
140
biological
fixation
140
denitrification
36
river flow
15
biological
fixation
groundwater
1200
internal cycling
8000
internal cycling
10
burial
SOIL
OCEANS
Nitrogen Cycle Without Microbes
<3
fixation in
lightening
?
human activities
ATMOSPHERE
200
denitrification
140
biological
fixation
140
denitrification
?
15
biological
fixation
river flow
groundwater
1200
internal cycling
SOIL
All processes slow.
Would life be possible?
8000
internal cycling
?
burial
OCEANS
Microbes
•Bacteria
•Fungi
•Protists
•Viruses
Bacteria
•Small
•Efficient
•Biochemically diverse
•Fast growth
Bacteria are everywhere
Cells/ ml or g
x106
Total cells
x1026
Marine
0.5
1,000
Freshwater
1.0
1.5
Sediments
4,600
170
0.34-200
38,000
1-105
0.0004
Subsurface sediments
(0-3,000 m)
Animal guts
(Whitman et al. 1998)
Global bacterial biomass (Pg of C)
Plants
Bacteria
Soil and Aquatic
Subsurface
Terrestrial
560
26
22-215
Marine
1.8
2.2
303
Microbial biomass rivals plant biomass
but has higher turnover
How many bacterial
species are there?
Wilson 1988
Total number species:
~ 1.4 million
Bacteria: ~3,500
Hammond 1995
Total number species:
~ 11 million
Bacteria: ~10 million
The great plate count anomaly
microbial community
plating
DAPI stained marine water sample
< 1% of observable bacteria grow on standard culture media
Genetic diversity
Total nucleic acids
16S ribosomal RNA genes
Sequences
Identification
and quantification
Diversity and
evolutionary relationships
Molecular approach:
• great diversity of microbes
• pathogens only a minor component
of microbial diversity
• allows understanding of evolution
of pathogenesis
Emergence of pathogens
What is a pathogen?
An evolutionary view.
Example: Escherichia coli (E. coli)
Normally a harmless gut bacterium but…
Eterotoxigenic strains
Enteropathogenic strains
Enteroinvasive strains
Enterohemorrhagic strains
Enteroaggregative strains
Uropathogenic strains
Genome analysis provides answer
Comparative analysis:
Strains closely related
Genome structure similar
But….
Insertions of ‘foreign’ DNA
= pathogenicity islands
Comparison harmless and
pathogenic E. coli strains
E. coli K12
E. coli O157:H7
A
B
C
A
B
C
Foreign DNA
= locus of enterocyte effacement
Responsible for pathogenicity:
allows attachment and toxin productions
A harmless bacterium has become a pathogen
by ‘stealing’ DNA from another bacterium!
Mechanisms of gene transfer:
2
1
3
1 Transformation: uptake of DNA from environment
2 Transduction: DNA transfer by viruses
3 Conjugation: plasmid transfer between bacterial cells
Can all transfer genes from other bacteria
that can become incorporated into genome
Fate of transferred genes:
recombination rate
RecA system = recombination into genome
dependent on sequence similarity
% sequence difference
How often does gene transfer happen?
Gene transfer is rare
e.g., transduction by viruses insert
foreign DNA every 108 virus infections
But….
Microbes have very large populations
e.g., gene transfer in marine environment
~20 million billion times per second!
Genes must be advantageous to recipient….
Ecology of pathogenesis
Bacteria grow fast
High population densities
Great competition for resources
Pathogen = normal bacterium
that has gained access to a new resource through new genes
--> Competitive advantage
Re-emergence of pathogens
Example 1: Antibiotics
Antibiotics - natural warfare
species 1
species 2
common resource
Example 1: Antibiotics
Antibiotics - natural warfare
species 1
species 2
antibiotic
common resource
Example 1: Antibiotics
Antibiotics - natural warfare
species 1
species 2
antibiotic
common resource
Example 1: Antibiotics
Antibiotics - natural warfare
species 1
common resource
Antibiotic resistance
Bacteria have evolved resistance genes to antibiotics
Located on plasmids
Plasmid encoded resistance is easily transferred
between species because plasmids are mobile
Occurrence usually low unless selection through
widespread antibiotic use
Antibiotics overuse creates ‘Superbugs’
50 million tons antibiotics per year
‘Superbugs’ resistant to most antibiotics
Example: Tuberculosis
2.5 million deaths
Mycobacterium tuberculosis
increasingly resistant
Example 2: Cholera and climate
Vibrio cholerae and other vibrios
ubiquitous in marine, coastal waters
Genetically similar non-pathogenic and
pathogenic strains co-exist
V.cholera
Vibrio species identified as
agents of human disease
GI
Species
V. alginolyticus
V. carchariae
V. cholerae
Non-O1
O1
V. cincinnatiensis
V. damsela
V. fluvialis
V. furnissii
V. hollisae
V. marinus
V. metschnikovii
V. mimicus
V. parahaemolyticus
V. vulnificus
a
++
++
Clinical presentations a
Wound/ear
Septicemia
Infection
++
+
+
(+)
+
+
++
++
++
++
(+)
+
?
++
++
+
?
+
+
++
(+)
++
GI, gastrointestinal; ++, most common; (+) very rare.
Seasonal cholera in Calcutta
(Sharma, 1998)
Vibrio infections
linked to El Nino
Dhaka, Bangladesh
Cholera cases
Seasonality
Removed
(Pascual, 2000)
Possible reasons for seasonality
Attachment to algae and zooplankton?
Temperature dependent growth?
Algal growth
= vibrio growth?
Temperature rise
= vibrio growth?
Links to global warming and/or pollution
Conclusions
Re-Emergence is an evolutionary/ecological phenomenon
Microbial communities extremely diverse
Large numbers of individuals
Potential for gene transfer
Pathogenesis arises via gene transfer
Result: harmless bacterial species becomes pathogen
because it gains competitive advantage
Ecological factors (resistance, alternate hosts, climate)
may trigger increased incidence of pathogenesis
Outlook for the future
Need to understand environmental
context of pathogenesis
Need to understand gene transfer
rates and diversity of co-occurring
genomes
Thanks to:
Silvia Acinas
Dan Distel
Dana Hunt
Vanja Klepac
Luisa Marcelino
Chanathip Pharino
Ramahi Sarma-Rupavtarm
Janelle Thompson
NSF, NIH, Seagrant, DOE - Genomes to Life