Bacteriel pathogenisis Flashcards
Relevance of bacterial pathogenesis
-historically high disease burden
-plague is still around
-new threats (new virulence factor combos and evolving bacteria
-climate change is altering range of vector
-antimicrobial resistance (no longer affected by antibiotics)
Modern big bacteria killers (2)
Tuberculosis and pneumonia
Story of bacterial ulcers?
-thought that there was no bacterial cause to ulcers
-Marshall ate food left out for days
-puked a lot, endoscoped stomach, found H. pylori
-won a nobel prize
H. pylori and ulcers
gram type, affected population, symptoms
-gram (-)
-infects 30-50% of population
-neutralizes stomach acid (production of urease
-inflammation + disrupted stomach mucosa = ulcers
-ulcers are linked to gastric cancer
Whats a pathogen
disease producer
Defining a pathogen?
Kochs postulates
Koch’s postulates + issues
-if present, causes disease (pathogens can be isolated from healthy individuals)
-isolate from diseased individual and cultured (some organisms are hard/impossible to culture)
-should cause disease when reintroduced to healthy organism (disease is dependant on external factors)
-should be reisolated from newly diseased patient
What factors determine whether a hsot bacteria interaction causes disease
Bacterial: route, number, virulence potential
host: host health, host genetics/genetics
Infection?
Pathogen is established in body
Disease?
infection produced signs and symptomsig
Signs vs symptoms?
Signs: observable by others
Symptoms: characteristis felt by patient
Asymptomatic carriage?
infection without disease
Opportunistic infection? +example
infection that would generally be cleared by system, but causes disease/death
e.g: pseudomonas in CF patients: thickened mucous in lungs prevents infection from being cleared
Secondary infection? +example
infection that develops in an individual already infected by another pathogen
e.g: TB in HIV patients
How can microbiomes affect susceptibility
colonization resistance (microbiome colony prevents pathogen from colonizing)
Steps of pathogenisis of bacterial diseases?
- Maintain a reservoir
- Be transported to the host
- Adhere to, colonize, and/or invade host
- Multiply or complete life cycles on or in host
- Evade host defenses
- Leave host and return to reservoir / enter new host
Reservoir? Types?
-habitat in which agent normally lives, grows and multiplies in
-humans (may or may not show effects of illness) animals or environment
specific to pathogen
Methods of transport pathogen to host
direct: direct contact & droplet spread
indirect: airborne, vehicle-borne, vector-borne
fomites?
inanimate objects in category of indirect, vehicule borne method of transport
Adherence?
Mediated by adhesins
Adhesins?
attach to specific strcutures: determine host susceptibility to pathogen
Colonization?
site of microbial reproduction in host
Invasion?
active penetration into or between host cells OR
passive penetration through unrelated means (bites, lesions…) or using host pathways of internalization (phagocytosis)
Multiply or complete life cycles on or in host? what does it depend on
pathogen must find appropriate environment (for some, theres mutliple options for this)
Evasion of host defenses by pathogen? types of defense (host) mechanisms and evasiont techniques
-complement system, phagocytosis, specific immune responses
-ex: bacteria capsule
Leaving the host: why, how
-perpetuating the microbe
-passive mechanisms (feces, urine…) usually aided by symptoms
Commensal strains vs pathogenic strains
commensal: rarely cause disease
pathogenic: can cause disease (different strains=different types of disease)
Virulence factors and ability to cause disease (4)
Can improve:
-colonization or invasion of host
-ability to multiply or complete life cycles
-ability to evade hsot defenses
-ability to leave and enter new host
Virulence factors (Molecular Koch’s postulates)?
-present in strains of bacteria causing disease (and vice-versa)
-disruption of gene reduces virulence
-reintroduction of gene restores virulence
-gene is expressed during infection
Aquisition of virulence factors?
-transposons
-pathogenicity islands
-plasmids
-phages
Examples of virulence factors?
-adhesins
-nutrient aquisition systems (ex: siderophores scavenge iron)
-capsule
-virulence asssociated secretion systems
-toxins
Anti-virulence drugs example
receptor decoys (works against adhesins)
T3SS? what, structure, bacteria type
virulence associated secretion system: injects bacterial proteins directly into host cells through syringe
flagellar basal body
gram (-) bacteria
Types of toxins
Endotoxin: part of bacterial cell
Exotoxin: secreted
Endotoxin: what, how is it toxic, what releases it, symptoms
LPS of gram (-) bacteria
Lipid A is toxic in high doses
Lysis of bacteria: increases host cell protein response, creating infmmation - can lead to sepsis (and fever)
Characteristics of endotoxins
Toxic to host in high doses
No enzymatic activity
Heat stable
Exotoxin example
Botulinum toxin (botox) - cleaves protein involved in neurotransmission from motor neurons to muscles (paralysis)
Characteristic of exotoxins | inactivated toxin
highly toxic
easily inactivated by heat
inactivated: can be used to elicit immune response (antitoxin)
Categories of exotoxins (2+2sub categories)
AB exotoxins: A=enzymatic activity B=cell binding/entry
membrane-disrupting exotoxins: poreforming or phospholipase
Intoxications?
disese resulting from the entry of a specifc preformed toxin (very fast onset)
Intoxication example:
Bacillus cereus: spore forming bacteria producing toxins that cause fast onset - grows in contaminated and improperly stored food
Vomiting
EHEC? reservoir, infectious dose, method of transmission
enterohemmoragic E. coli
cattle (ground beef or contaminated manure)
as little as 10 organisms
T3SS: injectiong of Tir, becomes receptor
EHEC symptoms and complications (HUC)
hemorrhagic colitis (bloody diarrhea)
0-20% of patients: hemolytic uremic syndrome
hemolytic anemia, platelet deficiency, kidney failure
HUS complications
50%: chronic renal problems
25%: neurological symptoms
3-5%: death
Shiga toxin: encoded in what, type/subunits,
EHEC (bacteriophages integrated in chromosome - prophage)
AB toxin: B-> glycolipids, A-> inhibits protein synthesis
EHEC treatment
no specifc treatment, lysing bacteria increases risk of HUC
treat the symptoms, watch and wait
EHEC prevention
handwashing, proper cooking of beef, safe food prep, pasteurization
