Bacteriel pathogenisis Flashcards by Ella Hamby

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)

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Modern big bacteria killers (2)

Tuberculosis and pneumonia

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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

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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

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Whats a pathogen

disease producer

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Defining a pathogen?

Kochs postulates

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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

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What factors determine whether a hsot bacteria interaction causes disease

Bacterial: route, number, virulence potential
host: host health, host genetics/genetics

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Infection?

Pathogen is established in body

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Disease?

infection produced signs and symptomsig

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Signs vs symptoms?

Signs: observable by others
Symptoms: characteristis felt by patient

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Asymptomatic carriage?

infection without disease

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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

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Secondary infection? +example

infection that develops in an individual already infected by another pathogen
e.g: TB in HIV patients

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How can microbiomes affect susceptibility

colonization resistance (microbiome colony prevents pathogen from colonizing)

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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

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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

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Methods of transport pathogen to host

direct: direct contact & droplet spread
indirect: airborne, vehicle-borne, vector-borne

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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