Title: How do we compete with pathogens?
1How do we compete with pathogens?
- Bacteria and viruses reproduce much more rapidly
- Bacteria and viruses are very numerous
- Bacteria and viruses tolerate vast fluctuations
in population size - Recover so quickly
- 1 of bacterial population is insignificant but
1 of human population is a major proportion - Enormous genetic diversity with rapid evolution
- Summary Pathogens have large populations that
undergo rapid fluctuation, evolving at a much
higher rate than their hosts.
2- Pathogens have a shared interest in our survival
with few exceptions, a dead host inhibits the
spread of the pathogen.
3Evolutionary mechanisms include intraclonal
(within the cell) and interclonal (between
different cells) processes.
4Intraclonal Processes
- DNA Replication microbes are constantly exposed
to chemical and physical mutagens, resulting in
high variation of genomes - RNA Replication no repair mechanisms means a
mutation rate so high that for many RNA viruses
virtually every particle is genetically different - Haploid Organisms single copy genomes means no
delay in expressing new genetic factors - Phase Variation many pathogens seem to have an
archive of genetic material that may be silent
under normal conditions but can become expressed
and give the appearance of an adaptive change
5Interclonal Processes
- Genetic Exchange conjugation, transduction, and
transformation increase the genetic, and often
the phenotypic, diversity - Host-Parasite Coevolution hosts and parasites
coadapt with parasites generally prolonging their
survival by overcoming host defenses and
mitigating their virulence - Symptoms symptoms may be a host defense or a
virulence mechanism
6The Germ Theory of Disease
7Foundations of Microbiology
- Antoni van Leeuwenhoek first observed
microorganisms - Louis Pasteur laid the foundation for modern
microbiology - Robert Koch developed methods and concepts
8Kochs Postulates
- The disease-causing organism must be present in
all diseased hosts and absent in healthy hosts. - The disease-causing organism must be isolated and
grown in pure culture. - Inoculation of a healthy host with the
disease-causing organism must result in the
original disease. - The disease-causing organism must be re-isolated
and shown to be the same as was inoculated.
9Ignaz Semmelweis
- Observed that mortality rate of new mothers was
higher with physicians than with midwives - Suggested better hygiene to reduce mortality
- Friend died of puerperal sepsis contracted during
autopsy - Hypothesized invisible agents responsible for
the spread of disease
10The Germ Theory of Disease
- Microbes are responsible for the spread of
disease.
11Leading Causes of Death in the U.S.
12Darwinian MedicineThe influence of evolution on
disease.
- How does a disease affect reproductive fitness?
- An inherited disease with a severe fitness cost
will be selected against.
When diseases have been present in human
populations for many generations and still have a
substantial negative impact on peoples fitness
they are likely to have an infectious
cause. ---- Paul Ewald
13Darwinian Medicine and Microbiology
- Evolutionary change occurs very rapidly in the
microbial world - Evolutionary drive is to reproduce
- Do reproductive and transmission strategies
influence disease symptoms? - Are disease symptoms caused by the pathogen or
the host?
14Evolution of Infectious Disease
- Too many copies of an infectious agent can kill
or immobilize a host before it can spread - Pathogens transferred by a vector tend to be more
virulent
15Chronic Diseases
Diseases that could not fulfill Kochs Postulates
were attributed to heredity, environmental, or
multifactorial causes
16Darwinian Medicine and Microbiology II
- Some of the diseases attributed to genetic or
environmental factors, including some forms of
heart disease, cancer, and mental illness, are in
many cases actually due to microbial infections.
17Heart Disease
- Clogged coronary arteries have been found full of
Chlamydia pneumoniae - Some estimates that 80 of coronary heart disease
is caused by C. pneumoniae - C. pneumoniae also found in autopsied brains of
Alzheimers patients (not in controls)
18HIV
- High mutation rate
- Preventative measures curb the spread of
infection - Would transmission-prevention programs be more
effective than the search for a vaccine?
19Cancer
- HTLV-1, a retrovirus endemic in parts of Asia,
Africa, and the Caribbean, has been linked to
some leukemias and lymphomas - Epstein-Barr Virus, the cause of mononucleosis,
has been linked to some lymphomas and
nasopharyngeal cancers - HPV has been shown to cause cervical cancer
- Hepatitis B and C have been linked to liver
cancer
20Ulcers
- Barry Marshall demonstrated that up to 75 of
ulcers may be due to Helicobacter pylori - Over 90 of cases are cured with antibiotics
- Infection by H. pylori causes a 6-fold greater
risk of stomach cancer
21Prediction from Ewald
- Throughout history most people have died of
infectious disease, and most people continue to
die of infectious disease.