3. Mycobacterium

Tuberculosis

caused by Mycobacterium tuberculosis

Leprosy

Mycobacterium leprae

Most bacterial pathogens cause what type of infection

Acute

Leprosy affects the

Nerves, skin, eyes, and nasal mucosa

Leprosy transmission

Very long, close contact with untreated person
ARMADILLOS

Leprosy treatment

Multidrug treatments for 1-2 years including rifampicin, clofazimine, and dapsone.

MTB

Mycobacterium tuberculosis

MTB transmission

small aerosol droplets containing between 1-3 bacteria

MTB reservoir

Humans, primarily pulmonary infections

Latent TB infection

person shows no symptoms and cannot transmit TB to others

Active TB infection incidence

10 million in the world have it and can transmit it to others

Active infection is more common with who

Smokers and people with HIV

MTB prevention

Bacillus Calmette-Guerin (BCG vaccine)

BCG vaccine

Only used for high risk ppl and is only 50% effective and causes scarring

MTB signs and symptoms

bloody cough, chest pain, consumption, fever, fatigue, etc

Consumption

Historic term for weightloss because infected person slowly withers away

Highest inidence for MTB

Africa and southeast asia

MDR MTB

Multi drug resistant tuberculosis infection, doesnt respond to 2 of 4 first line antibiotics

XDR TB

Rare, extensively drug-resistant tuberculosis, a severe form of TB that is resistant to 1 of 3 second line antibiotics

MTB treatment

Multiple antibiotics for 6-12 months

MDR TB is commonly resistant to

isoniazid and rifampicin – these are the 2 most important antibiotics used in treatment

XDR TB is commonly resistant to

isoniazid and rifampicin, PLUS any second-line drug like a fluoroquinolone or an aminoglycoside drug

Isoniazid

Targets mycolic acid synthesis in the bacterial cell wall, inhibiting growth of Mycobacterium.

Rifampin

Targets RNA polymerase in mycobacterial cells, preventing RNA synthesis and thereby inhibiting bacterial replication.

Fluoroquinolones

inhibit bacterial DNA gyrase, disrupting DNA replication and repair in Mycobacterium.

Aminoglycosides

inhibit protein synthesis by binding to the bacterial ribosome, effective against Mycobacterium tuberculosis.

MTB over the last 200 years

Has killed 1 billion people

Bedaquiline

Quinolone that targets MTB ATP synthase , used for drug-resistant tuberculosis treatment.

Mycobacterium is a ____ pathogen

Intracellular

M. leprae replication

Very slow. Division every 12-14 days!

M. tuberculosis replication

Every 18-24 hours

Mycobacterium are considered

Acid fast due to hydrophobic mycolic acids

Acid fast stain

Stains mycobacteria pink

MTB capsule is made of

Polysaccharide, protein, and lipid

MTB capsule function

Prevent dessication
Adherence
Resists host immune system

Mycobacterium gycolipids

PDIM and PGL

PDIM and PGL fuction

recruit MTB permissive macrophages
Reduce immune activation
Inhibits actin polymerization

MTB mycolic acids

Hydrophobic fatty acids found in the cell wall that contribute to the bacterium's resistance to desiccation and antibiotics.

MTB droplets

Smaller than 5 um, which easily reach the lower respiratory tract

Once MTB enters the lower lung, what happens

MTB is taken up by alveolar macrophages

MTB alveolar macrophages

NOT PERMISSIVE FOR MTB GROWTH

MTB PGL

Recruits CCR2+ macrophages

CCR2+ macrophages

Permissive macrophages which allow for intracellular MTB growth

PDIM MTB

Masks PAMPS to evade immune recognition
Dampens TLR signaling

Once inside a permissive macrophage, what happens with MTB

Through multiple routes, phagosomal acidification is blocked

Rab7 host

Protein which is essential for phagolysosome formation for host immune system

Rab7 MTB isoform

Nonfunctional rab7 which prevents lysosomal acidification

MTB TACO

Retained in MTB phagosome which releases calcium ions from phagosome to prevent acidification

MTB PknG

Serine-threonine kinase which inhibits lysosomal fusion

Granuloma

Macrophages are recruited to infected CCR2+ macrophages, deep in lung, forming a granulomatous structure that contains the infection.

Function of granuloma

attempt by the immune system to isolate foreign substances that it cannot eliminate

Early stage granuloma

Beginning of latent MTB infection

Late stage granuloma

can undergo necrosis, forming a necrotic core that supports bacterial growth and transmission to the next host. Exit from the granuloma often transitions the host to active MTB infection

Granuloma drug resistance

MTB are dormant inside granuloma which takes away replicating target
Also walled off from antibiotics

Tuberculosis necrotizing toxin (TNT)

Depletes NAD+ which prevents cells from making ATP in order to kill infected macrophages

M. leprae- Schwann cells

Infected the cells that form the myelin sheath around neurons. Infection leads to nerve damage, injury, and digit reabsorption.

Quiz next class

Granulomas- active vs late infection