Transcript Flower size (mm)

Resistance of Mycobacterium tuberculosis to
antibiotics

This bacterium that causes tuberculosis has been one of the scourges of
humankind
• Caused 25% of all deaths in New York City in 1804
• Caused 33% of the deaths in Paris in the 19th century

It still kills more people than any other viral or bacterial disease

However, improved nutrition and sanitation caused a decline in TB in
industrialized countries

The drugs rifampin and isoniazid are effective against the TB bacteria
Figure 21.6
Incidence of TB infections in 1997 (per 100,000 people)
Less than 10
10-24
25-49
50-99
100-250
More than 250

In the late 1980’s, the World Health Organization declared
TB a global health emergency

A number of strains of M. tuberculosis were largely or
completely resistant to rifampin and isoniazid

The case of an HIV-positive man in Baltimore provides
insight into the acquisition of resistance by M. tuberculosis

This man was diagnosed with an acute case of TB

A 39-month regimen of antibiotics resulted in clear x-rays of
his lungs and no sign of the bacteria in his body - the
antibiotics seemed to have cleared the infection

Two months later, the man was readmitted to the hospital
with tuberculosis-like symptoms

Despite aggressive antibiotic treatment, the man died 10
days later

The man’s physician and his research team analyzed the DNA from the
resistant M. tuberculosis from the man as well as DNA from M.
tuberculosis cells taken from the man when he was first admitted

The research team sequenced much of the DNA from the two strains and
found only a single difference, a point mutation at a locus that codes for
a portion of RNA polymerase (the protein that transcribes DNA to mRNA)

The mutation changed a TCG codon to TTG

The mutant RNA polymerase had leucine instead of serine at the 153rd
amino acid in the polypeptide chain

Rifampin acts by binding to the RNA polymerase of M.
tuberculosis

The substitution of leucine for a serine apparently kept the
rifampin from binding tightly to the RNA polymerase
The chain of events

The mutation arose early in the course of the infection

The mutant cells stayed at low frequency during the initial infection

After antibiotic treatment began, the mutant cells had a selective
advantage

The mutant cells grew in population size, eventually causing a relapse of
TB for the patient

Being resistant to rifampin, antibiotic treatment was ineffective
Did evolution by natural selection occur?

Was there variation in the population?
• Yes, there were resistant and non-resistant strains

Was this variation heritable?
• Yes, the researchers showed that the phenotypes of the two strains
were due to variation in their genotypes

Did natural selection occur?
• Yes, only a small fraction of the M. tuberculosis cells survived the first
round of antibiotics

When selection occurred, did a non-random subset of the population
survive better and reproduce more?
• It is clear that cells with the mutant allele conferring antibiotic
resistance increased through time
Figure 21.7 a,b
Number of individuals
In tundra habitats above timberline, the alpine skypilot is pollinated primarily by bumblebees.
28
24
20
16
12
8
4
0
10 12 14 16 18 20 22
Flower size (mm)
Tundra flower:
big and sweet-smelling
Number of individuals
In forested habitats below timberline, the alpine skypilot is pollinated primarily by flies.
Below-timberline flower:
small and skunky-smelling
10
8
6
4
2
0
10 12 14 16 18 20 22
Flower size (mm)
Figure 21.7a
Number of individuals
In tundra habitats above timberline, the alpine skypilot is
pollinated primarily by bumblebees.
Tundra flower:
big and sweet-smelling
28
24
20
16
12
8
4
0
10 12 14 16 18 20 22
Flower size (mm)
Tundra pollinator:
bumblebee
Figure 21.7b
Number of individuals
In forested habitats below timberline, the alpine skypilot is
pollinated primarily by flies.
Below-timberline flower:
small and skunky-smelling
10
8
6
4
2
0
10 12 14 16 18 20 22
Flower size (mm)
Below-timberline
pollinator: fly
Figure 21.8
110
100
Bee visits received
80
60
40
20
0
–4
–3
–2
–1
0
1
Size score
Small flowers
Short stems
Large flowers
Tall stems
2
Figure 21.9
1.0
Relative fitness (fecundity)
0.8
0.6
0.4
0.2
0
0
20
40
60
Bee visits received
80
100
110
Figure 21.10
18
Offspring’s flower size (mm)
16
14
12
10
8
8
10
12
14
Mother’s flower size (mm)
16
18
POLLINATION EXPERIMENT: CONTROL GROUP
1. Hand pollinate
a large, random
sample of skypilots.
2. Collect seeds;
germinate in
greenhouse
3. Plant seedlings
into randomly
assigned locations
in the field.
Number of individuals
Figure 21.11
16
12
8
4
0
9 11 13 15 17
Flower size (mm)
4. Measure flower
sizes and plot data.
Average = 13.1 mm
1. Allow bees to
pollinate a large
sample of skypilots.
2. Collect seeds;
germinate in
greenhouse
3. Plant seedlings
into randomly
assigned locations
in the field.
Number of individuals
POLLINATION EXPERIMENT: EXPERIMENTAL GROUP
16
12
8
4
0
9 11 13 15 17
Flower size (mm)
4. Measure flower
sizes and plot data.
Average = 14.4 mm