Consequences of Constraints (trade-offs in nature and evolutionary medicine)
What is a Life-History trade-off?
It is based on the concept that an organism cannot do everything well. Growth vs
Reproduction: trade –off between acquiring resources for growth and expending
resources for reproduction.
Trade-offs: examples from nature:
Industrial melanism and the peppered moth. Black colour is result of rare-
recurring mutation – black allele is dominant. Melanism provides camouflage
against dark backgrounds – melanic adaptation is environment specific (no one
phenotype is best in all environments). Change in background colouration (tree
bark) produces change in colour morph frequency.
Trade-offs: examples from human medicine:
MRSA, Tuberculosis, Feedlot microbes (Growth dependent on host resistance).
Viruses (Growth dependent on host species)
The First Antibiotic: Penicillin
How Penicillin kills bacteria: penicillin attaches to the cell walls of bacteria
and destroys a key molecular component of the cell wall. With its cell wall
disrupted, the bacterium dies.
Resistant bacteria are not killed by penicillin, because they have genes which:
1) alter cell walls to prevent binding by penicillin or 2) produce enzymes that
attack the antibiotic: degrade the penicillin.
MRSA: Multiple Drug Resistant S. aureus
Staphylococcus aureus grows and reproduces from 50 degrees F to 120
degrees F, with the most rapid growth occurring near body temperature (about
98 degrees F).
MRSA commonly occurs in the hospital setting but, more recently, community-
associated MRSA (CA-MRSA) has been found in correctional facilities and athletic
teams.
Extreme Drug-Resistant Tuberculosis: XDR-TB
TB was ‘conquered’ 50 years ago by streptomycin. Drug countries have not
invested in TB because it is a disease of developing countries. 9 million cases of
TB in the world, and WHO estimates that 2% of them (180,000) are XDR-TB. US
Centre for Disease Control reported 64 cases of XDR-TB; 21 ended in death.
South Africa: 53 cases of XDR-TB, 52 deaths.
The ‘Cost of Resistance’
There is a life history trade-off for bacteria between Antibiotic Resistance and
Reproductive Capacity in the absence of antibiotics.
The bacteria live in 2 environments:
, 1) The normal environment with a low level of natural antibiotics produced by
competing molds
2) The hospital, doctor’s office, or animal feed lot environment containing
enormous amounts of man-made antibiotics.
Evolution in 2 Environments:
2 kinds of bacteria:
1) ABS, Anti-Biotic Sensitive
2) ABR, Anti-Biotic Resistant
In the normal environment, E1: ABS bacteria grow faster than ABR because
reproductive capacity: bABS>bABR
In the environments with antibiotics, E2: ABR bacteria grow faster than ABS
bacteria because reproductive capacity: bABR>bABS
Use of Antibiotics:
Uncommon before 1950: antibiotic resistance favoured only in the common
environment, selected against everywhere else. Hence, there is a high frequency
of antibiotic resistant bacteria in 2006.
Common after 1950 (1970): antibiotic sensitive favoured only in the rare
environment, selected against everywhere else. Hence, there is a low frequency
of antibiotic sensitive bacteria.
1985: 6 million antibiotic prescriptions for sinusitis, Streptococcus pneumoniae
and Haemophilus influenza common upper respiratory tract bacterial species.
1992: 13 million prescriptions for sinusitis
1985: 15 million prescriptions for middle ear infections, Streptococcus
pneumoniae bacteria
1992: 23.6 million prescriptions for middle ear infections
Geometric growth of cases of CA-MRSA: CA-MRSA cases ranged from 0 to 9 per
year from 1990 through 1999 and then increased exponentially from 39 in 2000
to 459 in 2003.
Vancomycin: ‘the drug of last defence’: a S.aureus strain emerged that is
resistant to vancomycin. The first clinical infection with VRSA was reported in July
2002.
Feedlot use of antibiotics:
19 million pounds of antibiotics per year are fed to farm animals, and 88% of that
amount was fed at low doses, which favour evolution of antibiotic resistance
because they do not kill all bacteria in a colony
36 million antibiotic prescriptions at 1.5g per prescription = 54 million g
8.6 trillion g in feedlots vs 54 million g in prescriptions
Environmental Variation and Genetic trade-offs:
What is a Life-History trade-off?
It is based on the concept that an organism cannot do everything well. Growth vs
Reproduction: trade –off between acquiring resources for growth and expending
resources for reproduction.
Trade-offs: examples from nature:
Industrial melanism and the peppered moth. Black colour is result of rare-
recurring mutation – black allele is dominant. Melanism provides camouflage
against dark backgrounds – melanic adaptation is environment specific (no one
phenotype is best in all environments). Change in background colouration (tree
bark) produces change in colour morph frequency.
Trade-offs: examples from human medicine:
MRSA, Tuberculosis, Feedlot microbes (Growth dependent on host resistance).
Viruses (Growth dependent on host species)
The First Antibiotic: Penicillin
How Penicillin kills bacteria: penicillin attaches to the cell walls of bacteria
and destroys a key molecular component of the cell wall. With its cell wall
disrupted, the bacterium dies.
Resistant bacteria are not killed by penicillin, because they have genes which:
1) alter cell walls to prevent binding by penicillin or 2) produce enzymes that
attack the antibiotic: degrade the penicillin.
MRSA: Multiple Drug Resistant S. aureus
Staphylococcus aureus grows and reproduces from 50 degrees F to 120
degrees F, with the most rapid growth occurring near body temperature (about
98 degrees F).
MRSA commonly occurs in the hospital setting but, more recently, community-
associated MRSA (CA-MRSA) has been found in correctional facilities and athletic
teams.
Extreme Drug-Resistant Tuberculosis: XDR-TB
TB was ‘conquered’ 50 years ago by streptomycin. Drug countries have not
invested in TB because it is a disease of developing countries. 9 million cases of
TB in the world, and WHO estimates that 2% of them (180,000) are XDR-TB. US
Centre for Disease Control reported 64 cases of XDR-TB; 21 ended in death.
South Africa: 53 cases of XDR-TB, 52 deaths.
The ‘Cost of Resistance’
There is a life history trade-off for bacteria between Antibiotic Resistance and
Reproductive Capacity in the absence of antibiotics.
The bacteria live in 2 environments:
, 1) The normal environment with a low level of natural antibiotics produced by
competing molds
2) The hospital, doctor’s office, or animal feed lot environment containing
enormous amounts of man-made antibiotics.
Evolution in 2 Environments:
2 kinds of bacteria:
1) ABS, Anti-Biotic Sensitive
2) ABR, Anti-Biotic Resistant
In the normal environment, E1: ABS bacteria grow faster than ABR because
reproductive capacity: bABS>bABR
In the environments with antibiotics, E2: ABR bacteria grow faster than ABS
bacteria because reproductive capacity: bABR>bABS
Use of Antibiotics:
Uncommon before 1950: antibiotic resistance favoured only in the common
environment, selected against everywhere else. Hence, there is a high frequency
of antibiotic resistant bacteria in 2006.
Common after 1950 (1970): antibiotic sensitive favoured only in the rare
environment, selected against everywhere else. Hence, there is a low frequency
of antibiotic sensitive bacteria.
1985: 6 million antibiotic prescriptions for sinusitis, Streptococcus pneumoniae
and Haemophilus influenza common upper respiratory tract bacterial species.
1992: 13 million prescriptions for sinusitis
1985: 15 million prescriptions for middle ear infections, Streptococcus
pneumoniae bacteria
1992: 23.6 million prescriptions for middle ear infections
Geometric growth of cases of CA-MRSA: CA-MRSA cases ranged from 0 to 9 per
year from 1990 through 1999 and then increased exponentially from 39 in 2000
to 459 in 2003.
Vancomycin: ‘the drug of last defence’: a S.aureus strain emerged that is
resistant to vancomycin. The first clinical infection with VRSA was reported in July
2002.
Feedlot use of antibiotics:
19 million pounds of antibiotics per year are fed to farm animals, and 88% of that
amount was fed at low doses, which favour evolution of antibiotic resistance
because they do not kill all bacteria in a colony
36 million antibiotic prescriptions at 1.5g per prescription = 54 million g
8.6 trillion g in feedlots vs 54 million g in prescriptions
Environmental Variation and Genetic trade-offs:
