Flashcards in Intracellular Bacterial Infections Deck (12)
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1
Q
Advantages of intracellular lifestyle
A
- Nutritional:
- Pathogens avoid competition for space and nutrients with other microbes
- Downregulate genes important for citric acid cycle - rely on hosts for those
- Protection from immune system:
- Avoid a number of innate and humoral defenses
- Lack of sterilization allows some bacteria to lay dormant for decades, only to emerge under immunosuppressive conditions
- Such protection allows easy dissemination around the body
2
Q
Disadvantages of intracellular lifestyle within phagocytic cells
A
- Can be eaten up and digested by cell
- Phagolysosome: membrane-enclosed organelle that forms when phagosome fuses with lysosome
- After fusion, food particles/pathogens contained within phagosome usually digested by enzymes contained within lysosome
- Phagolysosome formation follows phagocytosis
- Harsh environment encountered inside phagocytes + slow growth characteristic of some intracellular pathogens –> chronicity of many of these infections
3
Q
Advantages of residing within non-phagocytic host cell
A
- Limited phagocytic and bactericidal activity by host cell
- Free ATP, free food, some good enzymes to play with and nothing is trying to actively kill it = good life.
4
Q
Strategies used by different intracellular pathogens to avoid antimicrobial defenses
A
- NADPH oxidase complex inhibition: prevents formation of complex
- e.g. Legionella pneumophila
- Detoxify reactive O2 species
- e.g. Salmonella
- Escape into cytoplasm from phagosome
- e.g. Listeria
- Increase natural resistance associated macrophage protein (NRAMP) homologues to help maintain nutrients within cell
- Limit expulsion of Fe2+ by phagosome
- Activated phagocytes usually reduce concentrations of iron available to intracellular pathogens to levels non-compatible with life
5
Q
Antibiotic considerations of intracellular bacteria
A
- Intracellular location of some microbes: critical aspect for failure of some abx for treatment of pathogens from infected hosts
- Intracellular activity of abx depends on:
- Penetration of eukaryotic membrane
- Subcellular localization
- Deleterious interactions with intracellular milieu, including pH
- Abx susceptibility of intracellular pathogen
- Weak base abx (aminoglycosides, macrolides) concentrated within lysosomes by pH-dependent mechanism
- Preferential localization within lysosomes and partial inactivation by acidic pH: major disadvantages
- Lack of peptidoglycan in cell wall of chlamydiae + intracellular lifestyle = poor activity of b-lactams
6
Q
Intracellular pathogens that escape into cytosol
A
- Listeria lyses phagocytic vacuole, escaping into cytosol
- Advantages:
- Access to large amounts of nutrients
- Minimize exposure to antimicrobial defenses associated within vesicles/phagolysosomes
- Disadvantages:
- Cytosolic antimicrobial peptides + cytosolic inducible NO synthase can target them
- Cytotoxic CD8+ T cells can lyse infected cells expressing microbial peptides on MHC I
- Intracellular movement: once in cytosol, Listeria hijacks actin (polymerizes) and uses it to motor around cytosol as well as invade neighboring cells without being exposed to extracellular compartment
7
Q
Intracellular pathogens that remain in vacuoles: fusogenic
A
- Fusogenic = fusion of phagosome with lysosome
- Bug is taken up and goes through entire maturation ultimately ending up in phagolysosome
- Coxiella burnetii, obligate intracellular Gram (-) bacterium
- Only intracellular pathogen to reside within phagolysosome
- Nascent phagosome matures through endocytic pathway, eventually acquiring properties of lysosomes
- Pathogen-containing vacuole acidifies
- Coxiella not cytopathic –> reaches very high numbers within single vacuole
8
Q
Intracellular pathogens that remain in vacuoles: non-fusogenic
A
- Several intracellular pathogens contained in membrane-bound compartments that avoid fusion with lysosome
- Mycobacterium, Legionella, Chlamydia
- No processing of bacteria to put on MHC
- Causes granuloma formation
9
Q
Genetic basis for classification of obligate vs. facultative intracellular pathogens
A
- Facultative microorganisms:
- Capable of both intra- and extracellular growth
- Obligate intracellular pathogens
- Have established such an intimate relation with their host that they cannot reproduce outside intracellular environment
- Loss of essential biosynthetic metabolic pathways = obligate dependency of host cells
10
Q
Obligate intracellular pathogens
A
- Chlamydia spp.
- Coxiella burnetii
- Ehrlichia spp.
- Mycobacterium leprae
- Rickettsia spp.
11
Q
Facultative intracellular pathogens
A
- Bartonella spp.
- Brucella spp.
- Francisella tularensis
- Legionella pneumophilia
- Listeria monocytogenes
- Mycobacterium spp.
- Nocardia spp.
- Salmonella enterica
- Shigella spp.
- Yersinia
Mnemonic: Listen Sally Yer Friend Bruce/Bart Must Leave Now
Listeria, Salmonella/Shigella, Yersinia, Francisella, Brucella/Bartonella, Mycobacterium, Legionella, Nocardia
12
Q
Zipper vs. trigger mechanisms contributing to invasion and dissemination of intracellular pathogens
A
- Can be taken by professional and non-professional phagocytes by zipper or trigger mechanism
- In both cases, reorganization of actin cytoskeleton results in changes at membrane surface, allowing uptake of bacteria
- Zipper:
- Tight interaction between bacterial cell surface ligands and host cell receptors –> closure of host cell surface around bacterium
- Trigger:
- Bacterial products induce cell surface to ruffle, projecting membrane extensions that surround bacteria
- Products secreted by type III secretory systems of Salmonella and Shigella induce this kind of uptake
