Niche Selection

Question 1

What are the different niche selection types?

Answer 1

Specialist: narrow niche, highly adapted, vulnerable to change (H. pylori)

Generalist: broad niche, metabolically flexible (e.g. S. aureus)

Question 2

What is the niche conditions of H. pylori?

Answer 2

Colonises gastric mucosa:
- Acidic
- Mucus-rich

Question 3

What range of pH does H. pylori prefer?

Answer 3

5.5-7.5
It cannot grow well in fully acidic conditions

Question 4

How does H. pylori survive is the acidic conditions of the stomach?

Answer 4

• Flagella & spiral shape grant motility, can swim through thick mucus lining of stomach to areas with a more neutral pH
• Urease enzyme breaks down urea (into ammonia and bicarbonate), which raises local pH

Question 5

What helps H. pylori evade immune killing?

Answer 5

• Urea cycle metabolises arginine, depleting nitric oxide production in macrophages (since NO is made from arginine)

Question 6

How significant is urease for H. pylori?

Answer 6

Essential to allow survival. Not only makes less acidic, but also involved in reducing mucus viscosity to aid motility.

Makes up 10-15% H. pylori proteome (proteins expressed)

Question 7

What is the pathogenic advantage of the specialised niche of H. pylori?

Answer 7

Survives in a habitat that is hostile to most microbes.
Reduces competition for nutrients

Question 8

What is the niche of M. tb?

Answer 8

Macrophage phagosomes- low nutrients, immune pressure

Question 9

What percentage of Mtb genome is dedicated to fatty acid metabolism?

Answer 9

Up to 5%

Question 10

What does Mtb use as carbon/energy sources for metabolism?

Answer 10

• Host fatty acids
• Cholesterol
  (lipid-based aerobic metabolism)

Question 11

What are foamy macrophages?

Answer 11

Lipid-laden macrophages that can be induced by Mtb- act as nutrient reservoirs for the pathogen

Question 12

What is the outer wall of Mtb made of?

Answer 12

Mycolic acids- long chain fatty acids that form a thick cell wall that is impermeable to immune pressure & antibiotics

Question 13

How does Mtb use the lipids?

Answer 13

• Energy (oxidation and TCA cycle)
• Carbon source for biosynthesis of mycolic acids

Question 14

Where are lactobacillus species found?

Answer 14

Gut and vaginal microbiome

Question 15

What type of metabolism does Lactobacillus use?

Answer 15

Lactic acid fermentation- converting glucose -> pyruvate -> lactic acid

Question 16

Why is the metabolism of Lactobacillus important?

Answer 16

Creates an acidic environment that inhibits the growth of competing pathogens, like Candida and E. coli.

Low pH is protective against infections for the host, especially in vaginal tract

Question 17

What is the niche of Staphylococcus aureus?

Answer 17

Many parts of the body, including nose, skin and even bloodstream.

Question 18

Why is S. aureus able to grow in many different areas?

Answer 18

It is a metabolically versatile, facultative anaerobe.

It is able to switch between different nutrient sources, dependent on availability

Question 19

What are some different carbon sources that can be used by S. aureus?

Answer 19

• Glucose
• Amino acids
• Glycerol
• Even nucleosides can be metabolised under extreme nutrient stress

Question 20

What is an essential nutrient for S. aureus?

Answer 20

Iron: crucial for survival and virulence

Question 21

What are the iron uptake systems used by S. aureus?

Answer 21

• Siderophores
• Haem uptake from haemoglobin

Question 22

What are the siderophores of S. aureus?

Answer 22

Staphyloferrin A and B

Question 23

How does the generalist nature of S. aureus play into its infections?

Answer 23

Colonisation of diverse environments contributes to its role as a major opportunistic pathogen

Question 24

What is the iron competition for S. aureus in the nasal microbiome?

Answer 24

Competition is intense in the nasal microbiome due to the limited access to key nutrients like iron

Question 25

How do commensal bacteria interfere with S. aureus iron uptake?

Answer 25

- Some commensal engage in siderophore piracy (uses S. aureus siderophores for themselves) - Other produce proteins that sequester S. aureus siderophores to block access The diversity of the microbiome directly influences the ability of S. aureus to persist and cause disease

Question 26

What is a current example of how bacterial metabolism can act as a target for antibiotics?

Answer 26

Existing drugs (like sulfonamides) inhibit folate synthesis pathway, which is essential for DNA replication. Humans acquire folate from diet, making it a bacteria-selective target

Question 27

What are some emerging antibiotic strategies?

Answer 27

Mimicking of nutritional immunity- depriving bacteria of iron. Blocking pathogen-specific nutrient transporters

Question 28

What is an example of ongoing research into nutritional immunity as a antibiotic strategy?

Answer 28

Ongoing research into iron uptake inhibition or lipid metabolism interference in M. tuberculosis

Question 29

Other than restricting NO synthesis in macrophages, what does urea cycle in H. pylori permit?

Answer 29

Maintenance of internal pH and nitrogen levels

Question 30

What is the impact of urease on motility?

Answer 30

- Increasing the pH changes the composition of protective mucus layer, making it less viscous - Makes it easier for H. pylori to penetrate the mucus to attach to the epithelial cells underneath