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

Incidence of TB infections in 1997 (per 100,000 people)

Less than 1010-24

25-49

50-99100-250More than 250

Figure 21.6

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

In tundra habitats above timberline, the alpine skypilot is pollinated primarily by bumblebees.

In forested habitats below timberline, the alpine skypilot is pollinated primarily by flies.

Below-timberline flower: small and skunky-smelling Flower size (mm)

Nu

mb

er o

f in

div

idu

als

10 12 14 16 18 20 22

10

8

6

4

2

0

Tundra flower: big and sweet-smelling

Flower size (mm)

Nu

mb

er o

f in

div

idu

als 28

24201612 8 4 0

10 12 14 16 18 20 22

Figure 21.7 a,b

Tundra flower: big and sweet-smelling

In tundra habitats above timberline, the alpine skypilot ispollinated primarily by bumblebees.

Tundra pollinator: bumblebeeFlower size (mm)

Nu

mb

er o

f in

div

idu

als

2824201612 8 4 0

10 12 14 16 18 20 22

Figure 21.7a

In forested habitats below timberline, the alpine skypilot ispollinated primarily by flies.

Below-timberline flower:small and skunky-smelling

Below-timberline pollinator: flyFlower size (mm)

Nu

mb

er o

f in

div

idu

als

10 12 14 16 18 20 22

10

8

6

4

2

0

Figure 21.7b

Large flowersSmall flowers

Short stems Tall stems

–3 –2 –1 0 1 2–4

Size score

110

100

80

60

40

20

0

Bee

vis

its

rece

ived

Figure 21.8

0 20 40 60 80 100 110

Bee visits received

1.0

0.8

0.6

0.4

0.2

0

Rel

ativ

e fi

tnes

s (f

ecu

nd

ity)

Figure 21.9

8 10

8

10

Mother’s flower size (mm)

Off

spri

ng

’s f

low

er s

ize

(mm

)

12 14 16 18

12

14

16

18

Figure 21.10

9 11 13 15 17

9 11 13 15 17

0

4

8

12

16

0

4

8

12

16

Nu

mb

er o

f in

div

idu

als

Nu

mb

er o

f in

div

idu

als

Flower size (mm)

Flower size (mm)

4. Measure flower sizes and plot data.Average = 13.1 mm

4. Measure flower sizes and plot data.Average = 14.4 mm

3. Plant seedlingsinto randomly assigned locations in the field.

3. Plant seedlingsinto randomly assigned locations in the field.

2. Collect seeds;germinate ingreenhouse

2. Collect seeds;germinate ingreenhouse

POLLINATION EXPERIMENT: CONTROL GROUP

POLLINATION EXPERIMENT: EXPERIMENTAL GROUP

1. Hand pollinate a large, randomsample of skypilots.

1. Allow bees to pollinate a largesample of skypilots.

Figure 21.11

1m

The dolphin and ichthyosaurlineages are far apart on theevolutionary tree, suggestingthat they are not closelyrelated

Lizards

Ichthyosaurs

Birds

Dinosaurs

Pterosaurs

Ichthyosaur1m

Elephants

Whales and

dolphins

Primates

Rodents

Marsupials

Common dolphin

Monotremes

Analogy: When similarities result from convergent evolution

Synapsids

The members of lineagesbetween the dolphins andichthyosaurs do not haveadaptions like:- streamlined bodies- long jaws filled with teeth- fins and flippers

Box 21.2 Figure 1a

Fruit fly HOM complex

lab pb Dfd AntpUbx

Flat

wor

ms

Art

hrop

ods

(inse

cts,

spi

ders

,

cru

stac

eans

)

Ann

elid

s

(seg

men

ted

wor

ms)

abdAabdB

Mol

lusc

s

(sna

ils, c

lam

s,

squ

id)

Homology: When similarities are inherited from a common ancestor

b-1 b-2 b-3 b-4 b-5 b-6 b-7

Echin

oder

ms

(sea

sta

rs,

san

d do

llars

)

Human Hox complex

Cho

rdat

es

(ver

tebr

ates

)

b-8 b-9

As shown in the two boxesabove, the loci found in theHox and HOM complexesof fruit flies and humans havesimilar sequences and are in the same order on their chromosomes

Box 21.2 Figure 1b