Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

LF223: Microbial Pathogens > Lecture 9. Slow Growing Mycobacteria; Mycobacteria leprae > Flashcards

Lecture 9. Slow Growing Mycobacteria; Mycobacteria leprae Flashcards

1
Q

How long is the doubling time of slow-growing mycobacteria?

A

No less than 16 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are most slow-growing mycobacteria?

A

Harmless, environmental bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What have a few slow-growing mycobacteria evolved into?

A

Major human pathogens (M. tuberculosis, M. leprae, M. ulcerans are all chronic diseases)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does Mycobacteria tuberculosis cause?

A

Tuberculosis - world’s deadliest infectious disease (briefly eclipsed by Covid-19)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does Mycobacteria leprae cause?

A

Leprosy (Harman’s disease)
Affects skin, nerves, eyes and respiratory tract
Documented in ancient literature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does Mycobacteria ulcerans cause?

A

Buruli ulcer
Affects the skin and sometimes bone
Can lead to permanent disfigurement and long-term disability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is a feature of mycobacteria?

A

Genomes are small and lose chunks over millions of years of evolution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What makes mycobacteria diseases so pathogenic?

A

Low infectious dose (1 cell, having a low infectious dose increases the chances of a parasite being pathogenic)
Intracellular pathogens (so can be considered parasites) - in macrophage
Resistant cell wall
Subvert the human immune system (mycobacterial cell surface components stop phagosome killing)
Form characteristic granulomatous lesions (Immune cell cluster limiting mycobacterial invasion which mycobacteria can survive within)
Slow-growing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is a granuloma?

A

What host immune cells cluster into to fight infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where are mycobacteria located within the phagosome?

A

Inside the macrophages in centre of granuloma, contained but surviving
Surpasses phagosome killing
Balance between the host and pathogen can vary (mycobacteria can be contained or overtaking granuloma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is special about the mycobacterial cell wall?

A

Acid fast stainin
Neither Gram positive nor Gram negative
Thick, waxy, hydrophobic cell envelope, makes it really resistant to host immune system and most antibiotics
Resistant cell wall means mycobacteria can survive for months or even years in the environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the challenges of developing treatments/drugs for mycobacteria?

A

Resilient to most antibiotics
Drugs are available that treat mycobacterial infections
Resistance develops through mutation
Long term treatment with antibiotic mixtures necessary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What vaccine can be used to provide partial protection to mycobacteria and in what age group is it most effective?

A

The vaccine BCG offers partial protection, particularly to children

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why do vaccines work poorly when treating mycobacteria?

A

The immune evasion strategies of mycobacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the symptoms of leprosy?

A

Loss of sensation in hands and feet
Leading to disability through injury
Blindness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can leprosy be cured?

A

With multi-drug treatment regimes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Besides Mycobacterium leprae, what other causative agent can cause leprosy?

A

M. lepramatosis (discovered in 2008)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When was M. leprae identified as the causative agent of leprosy and what was leprosy considered to be prior to this discovery?

A

1873, previously been considered a hereditary disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why does leprosy have a stigma?

A

Widespread misunderstanding of how the disease works (not highly contagious)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is leprosy typically caught?

A

Via close contact over an extended period and is mainly spread through droplets from the nose and mouth by coughing and sneezing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where is leprosy endemic to?

A

Central Africa, Southeast Asia and South America

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How many new cases of leprosy are there per year globally?

A

200,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How many children are diagnosed with leprosy annually?

A

15,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How many people are estimated to have leprosy-related disabilities globally?

A

2 to 3 milion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Where were half of all new cases of leprosy cases diagnosed?
India, home to a third of the world’s poor - a group disproportionately affected by the disease
26
How is M. leprae transmitted?
Not fully clear?
27
What animal has been shown to transmit M. leprae to humans in the US?
Nine-banded armadillos (represent possible zoonotic reservoir)
28
What animal might be a zoonotic reservoir for M. leprae in the UK??
Red squirrels Only recently detected (2008) No known squirrel-human transmission case
29
What is M. leprae the intracellular parasite of?
Keratinocytes Nerve cells Dendritic cells Macrophages
30
Why is our understanding of leprosy pathogenesis and interaction with the host limited?
We are unable to culture the bacterium in vitro
31
How many people show no symptoms for leprosy and clear the disease?
95%
32
What is the spectrum of leprosies that are classified depending on symptoms and severities?
From tuberculous to lepromatous leprosy (tuberculoid is where macrophage is activated, lepromatous is where macrophage is suppressed)
33
What are the symptoms of lepromatous leprosy?
Extensive sensory loss over a longer period More severe disease and larger numbers of bacteria Facial deformities and paralysis Involvement of eyes, bones, and other tissues
34
What is lepromatous leprosy characterised by?
By a Th2 T-cell immune response
35
What occurs in lepromatous leprosy?
Antibody complex formation The absence of granulomas Failure to restrain M. leprae growth. Robust antibody formation occurs but is not protective Cell-mediated immunity is conspicuously absent (eg activation of macrophages)
36
What does tuberculoid leprosy feature?
Th1 T-cell cytokine response
37
What occurs in tuberculoid leprosy?
Vigorous T-cell responses to M. leprae antigen Containment of the infection in well-formed granulomas
38
What is the full clinical spectrum of leprosy disease?
Tuberculoid (TT) Borderline tuberculoid (BT) Borderline borderline (BB) Borderline lepromatous (BL) Lepromatous (LL)
39
What is each type of leprosy characterised by on the spectrum?
Characteristic cell-mediated or humoural immune profile
40
What type of pathogen is M. leprae and what does it have a distinct preference for?
Obligate intracellular pathogen with a distinct preference for Schwann cells of the peripheral nervous system and for macrophages
41
What is the mechanism for M. leprae nerve damage?
Unclear but could be any of the following Ischemia: restricted blood flow Apoptosis: Programmed cell death Demyelination: Loss of myelin sheath
42
What are Schwann cells?
Cells of peripheral nervous system that produce the myelin sheath around neuronal axons
43
How did M. leprae originally infect humans?
Likely that the leprosy bacilli started parasitic evolution in humans or early hominids millions of years ago Makes leprosy the oldest human-specific infection
44
How did M. leprae co-evolve with humans?
Reductive evolution – loss of functional genes Evolved to increasingly parasitic lifestyle, resulting in only being able to grow within host cells Lean genome (3.27 Mb) was much smaller (>1 Mb) than that of related Mycobacterium tuberculosis It contained around 1,600 pseudogenes with loss of ~50% of the ancestral genes Pseudogenes are considered as molecular fossils
45
Why does susceptibility to leprosy vary?
Multiple single nucleotide polymorphisms (SNPs) involving many genes have been found to be associated with increased or decreased protection. This also means protection to leprosy can be inherited
46
What mutation protects people from leprosy and why?
Toll-like receptor 1 (TLR1) mutation from isoleucine to serine at AA 602, homozygous individuals protected against leprosy. Immunity suggests TLR1 part of pathogenesis mechanism for leprosy (TLR1 isI ivolved in immune response/signalling in macrophage)
47
How is leprosy diagnosed?
At least one of: Definite loss of sensation in a pale (hypopigmented) or reddish skin patch Thickened or enlarged peripheral nerve, with loss of sensation and/or weakness of the muscles supplied by that nerve Microscopic detection of bacilli in a slit-skin smear
48
What is paucibacillary (PB) leprosy?
A case of leprosy with 1 to 5 skin lesions, without demonstrated presence of bacilli in a skin smear
49
What is multibacillary (MB) leprosy?
A case of leprosy with more than five skin lesions; Or with nerve involvement (pure neuritis, or any number of skin lesions and neuritis); Or with the demonstrated presence of bacilli in a slit-skin smear, irrespective of the number of skin lesions
50
What does leprosy treatment depend on?
Whether you are dealing with PB or MB leprosy
51
In 1981, what did the WHO recommend for treating leprosy and for how long?
Multi-drug therapy consisting of dapsone, clofazimine, and rifampin 6 months treatment for PB and 12 months for MB
52
Why is it important for leprosy to be diagnosed early on and prompt treatment?
To prevent disabilities
53
What problems arise when using the three drugs used to treat leprosy?
Resistance is emerging to all 3 drugs (dapsone has been used since 1945) Some cases relapse several years after therapy completed Second line drugs are available if resistance to MDT arises
54
What is dapsone?
A sulfone antibiotic Inhibitor in the folate synthesising enzyme system Folic acid is necessary for bacteria and humans alike Bacteriostatic
55
How can resistance to dapsone arise?
Resistance can arise through point mutations on gene (folP1) for target enzyme
56
What is rifampicin?
Ansamycin class of antibiotics Semisynthetic as it is modified from the natural product rifamycin Action is as an RNA polymerase inhibitor Blocks bacterial transcription
57
What is common with taking rifampicin?
Side effects
58
How can resistance to rifampicin arise?
Resistance occurs through mutations at binding site of rifampicin on RNA pol
59
What is clofazimine?
Synthesised for 70 years Molecular mode of action against mycobacteria unclear Anti-inflammatory Resistance can occur through over expression of transporters
60
How can leprosy be prevented?
Community awareness is key Case detection and treatment with MDT WHO recommends tracing household contacts along with neighbourhood and social contacts of each patient Administration of a single dose of rifampicin as preventive chemotherapy to close contacts BCG vaccination given primarily for TB may offer some protection against leprosy
61
What does the stigma of leprosy affect?
The stigma of leprosy affects the physical, psychological, social, and economic well-being of those with leprosy, contributing to the cycle of poverty in the affected regions
62
What aims are set in place to eradicate leprosy?
Implement integrated, country-owned zero leprosy road maps in all endemic countries Scale up leprosy prevention alongside integrated active case detection Manage leprosy and its complications and prevent new disability Combat stigma and ensure human rights are respected

LF223: Microbial Pathogens (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions