Bacterial Pathogenesis and Control of M/O Flashcards
Why study bacterial Pathogenesis
Understandung how bact cause disease help dev. of method to control
Climate change alter range of pathogens, antimicroial pathogens
Bateria cause of Ulcers
Ulcers were thought to be caused by stress and no one believed Dr. Barry Marshall that is a bact cuz stomach is acidic and it was hard to culture… but he cultured them and then he drank it and treated itself and confirmed the hypothesis=Nobel Prize
Helicobacter pylori and ulcers
GRam -
Infect 30-50% of pop
Majority=asymptomatic
Neutralize stomach acid by producing urease
Cause inflammation, disrupts stomach mucosa=cause gastric ulcers
STrong link to gastric cancer (only carcinogen bact. in WHO)
What is a pathogen
Continuum
BEnegicial: probiotics/Commensal
Neutral
Can be harmful: Pathobionts (opportunistic pathogens)
Harmful: PAthogens (Koch’s postulat: organisms only in infected, never healthy, isolate from infected and reinjected in healthy)
What cause disease+
Terminology (Infection vs disease vs symptoms vs signs)
Bact. factors: Route, #, Virulence Potential
Host factors: Host health status, Host defense/genetics
Some beneits us by coloinzation resistance (keep pathogen at bay because “no space”)
**Infection: Pathogen establishes in body
Disease: Infections with signs(Objective manif observed/mesured by others) and symptoms (Subjective characteristics felt by patient)
Asymptomatic carriage: Infection w/o diseases
Sndary infection: Infection that develops in an indiv who is alr infected with diff pathogen
Pathogenesis of bacterial disease (steps)
1- Maintain a reservoir
2-Be transported to the host
3-ADhere to, coloniz and/or invade host
4-Multiply/complete life cycles on/in host
5-Evade host defense
6-Leave host and return to reservoir or enter new host
1-Maintain a reservoir
Rerservoir= habitat where agent normally live, grow, multiply… may(or not) be the source which an agent is trasnferred to host
A carrier=person with inapparent infection who is capable of transmitting the pathogen to other
Human reservoir (may or ont show symptoms)(Typhoid Mary for Salmonella typhi)
Animal (ex. cow: E. coli or Poultry: Salmonella)
Env (soil: C. tetani)
Typhoid MAry
Cook… bacteria transmitted by oral so everyone got sick, she refused to stop working and finally was forcefully quarantined
Step 2: TRansport of the bacterial pathogen to the host
Direct
Contact (skin-skin or kissing…)
Droplet spread (sneezing, takling, large/short range…)
Indirect
Airbone (small particle suspended in air for long)
Vehicle-borne (Indirectly transmit an infectious agent-food, water, bio produc as blood, fomite(inanimate objects)
Vector-borne (living beings as mosquitos… may carry an infectious agent thru purely mechanical means or may support growth or changes in the agent)
Step 3: Adherance/Colonization/ Invasion
Adherance: Mediated by mol/struc=adhesines
Colonization: Establishment of a site of microbial reproduction on/within host
Invasion:
-can be active penetration into host cell
-Can be active penetration between host cells
-Can be passive (Not related to pathogen itself (wounds, insect bites…) or can use existing host pathways of internalization (ex. phagocytosis)
Types of adhesins and info
Non-fimbrial (small embedded)
Fimbriae (Spaghetti)
Type IV pili (Thicker spaghetti)
Curli (Rope-ike intertwined fingers)
Attach to specific struc on host cell
P, glycoP or glycolipids
Presence/Absence of receptor can determine host susceptibility
only one aa makes the diff and make one susceptible
Step 4: Multiply or complete life cycle on or in host
Occurs when pathogen fins appropriate env (nutrient, pH, T°, redox potential, protection) withing host… place depend on pathoges
Some have evolved to survive and multiply in diff env in host
Multiply/complete life cycles on/in host: Intra/Extra¢ar pathogens, some incade specidic ¢ (adapted strategies to live insided)
STep 5: Evasion of Host Defense by bact
Must have mechanisms to resis host defenses like: complement sys, phagocytosis, specific immune response
Ex. : Bacterial capsule: composed of chem not recognized as foreign, its slippery and diff to engulf by phagocyte
Step 6: Leave the host
If microbe is to be perpetuated
Most leave by passive mechanism (feces, urin, droplet, saliva…)
Symptoms helps in this: Runny nose, sneezing, coughing, diarrhea
Virulence factors confer an increased ability to cause disease
Improve:
1- Colonization or invasion of host
2- Ability to multiplu and complete life cycle or/in host
3-Ability to evade host defense
4- Ability to leave host and enter new host
Acquision of bacterial virulence factors and types
TRansposon, plasmid, phage, pathogenecity island-Can be commensal
Adhesins (cehck pic)
Nutrients acquisition sys (bacterial siderophore scavenge iron, which is in limiting quantities in the host)
Capsule (outside ¢ wall, usually polysasccharide or other, protect phagocytosis by host ¢)
Virulence-associated secretion systems (Translocated “effector” P)… (exist several diff type: type III secresion sys (T3SS))
Toxins (exotoxins: secreted endotoxins: part of the bacterial cell-LPS of Gram negative)
T3SS
Encoded by approx. 20 gene
Present in GRam neg pathogens
Inject bacterial P(vary between diff bact) directly into host ¢ (“Syring” gene=similar between diff species)
Cellular effect vary between bact
Endotoxins: LPS of Gram negative bact
STructure component of gram neg OM, released when bact lyses (bacterial multiplication)
Toxic component (tocix only at high doses)=Lipid A
HEat stable… toxic only at high dose
Effect are indirect (no enz act onhost… interaction with host cell thru binding of a receptor complex.. induced transcriptional response in the host ¢)
Increased production of host ¢ P which produce sever host-mediated inflammatory response (in case of spsis=fever, high heart rate…)
EX of exotoxin
Botulinum toxin (clostridium botulinum)=most posionous naturally occuring substance in the world
Ckeaves a P involved in neurotransmission from motor neurons to muscles (double biision, paralysis, muscle weakness
exotoxins characteristics and categories
Usually easily inactivated (ex. heat)
Inactiated tocun can be used to elicit immune response
Tocun=specific antiserum can be sused to treat disease
Antitoxin= antibody used to neutralize a specific toxin
AB exotoxins, membrane-disrupting exotoxins, superantigens(stimulate T cellls>exxagerated immune response)
(can also be categorized by site of action, neurotoxin or enterotoxin…)
AB toxins
A subunit=has an enzyme act and is responsible for toxic death
B subunit= mediate cell Binding to specific receptors on target cells/entry
Both act and bindinf can vary depending on specfoc toxin
Diveristy: Diff receptors on host cell, Diff enz act, diff bio eggect, similar overall org
MEmbrane-disrupting exotoxins
Attack host cell membrane
Pore forming
Phospho-lipases
check pic
