-
virulence factors
- invasiveness
- infectivity
- toxigenicity
-
invasiveness
motility, flagella
-
infectivity
- adherence (adhesion proteins and pilli)
- capsules
-
pathogenic potential (Toxigenicity)
secretion of toxins
-
host parasite relationship factors
- number of organisms present
- degree of virulence
- host defenses or degree of resistance
-
Primary vs opportunistic
- Primary - usually causes disease
- Opportunistic - isn't in the right place, or over grows, if considerations are right.
-
zoonoses
the transfer of disease between species
-
-
steps to disease
- 1) maintain a reservoir
- 2) transport to host
- 3) adhere to, colonize, and/or invade host
- 4) evasion of host defenses
- 5) multiple or complete the life cycles on or in host
- 6) damage host
-
1) maintain a reservoir
humans, animals, and environment
-
2) transport to host
direct and indirect contact
- Indirect: vehicles (soil, food, and water),
- arthropods, and fomites
-
3) attachment and colonization
pilli, fimbrae, capsule and slim layer, and s layer
also charged molecules hanging outside of the cell, help it adhere
-
4) Evasion
- prevention of fusion process
- secretion of pore forming proteins (to colaspe lysome)
- evading the complement system (moditification of proteins)
- antigen variation, a race to out modify the immune system
-
active vs passive invasion
active - secretion of an enzyme tobreak down host's barrier.
passive - through a scrap or puncture by an arthropod.
-
pathogenicity islands
genes that cause pathology
genes that encode the virulence factors
-
endotoxins vs exotoxins
endotoxins - usually gram negative, toxins are in cell wall
Exotoxins - secreted proteins ofter gram postive, some of the most potent toxins.
-
Name the four types of exotoxins
- 1) AB exotoxins (B binds) (Not all AB are type 2)
- 2) Specific host site bonding (many are AB)
- 3) membrane disrupting exotoxins (pore forming or degrade membrane)
- 4) superantigens (overactivates the immune system)
-
three types examples of host site specific.
- 1) neurotoxins (neurvous system, Botulism, tetanus)
- 2) enterotoxins, (vibrocholerae cholera)
- 3) cytotoxins (cell death, diphtheria, AB, no ribosomal created protein)
-
membrane disrupting exotoxins, two types
- 1) pore forming exotoxins
- hemolysins from streptococcus and s. Aureus.
- 2) Phospholipases
- causes necrosis of tissues
- Gangrene is caused by clostridium profrengenes
-
superantigens
the over reaction of the immune system
a toxins triggers the t-cell response without the antigen presenting cell (APC)
toxic shock syndrome (icky tampon!)
-
endotoxins
lipopolysaccharides (LPS) - lipid A portion of the LPS causes the disease
- t-cell binds to the lipid A portion
- not as potent as exotoxins, yes.
-
describe chemotherapeutic agents and what are they selectively toxic to?
they are used to treat disease. They are selectively toxic to 16S Ribosomal DNA in prokaryotes, we have 18S rDNA
-
When and to what gram type of cell is penicillin most effective?
Gram positive in the log phase.
-
What is streptomyocin effective against?
Turbcurlosis (TB), kills more microbes. Targets SS ribosomes.
-
Why is penicillin ineffective against TB?
thick mycolic acid, stains g(+), but more like gram (-)
-
general characteristics of antibiotics
- selective toxicity
- therapeutic index
(toxic dose)/(therapeutic does) = TI
-
level of antimicrobial activity
- 1) minimal inhibitory concentration (MIC)
- where no growth was seen
-
- 2) minimal lethal concentration (MLC)
- Where subculture does not grow
-
Four different ways of detecting antimicrobial activity
- 1) Dilution susceptibility test
- Different concentrations of the drug in the media, differentiates the MIC from the MLC
- 2) Disk diffusion test (Zone of inhibition)
- Cannot compare Zone of inhibition directly across different antibiotics)
- 3) Kirby-Bauer method
- Standardized method that compares disk diffusion to the degree of microbial resistance.
- 4) Epsilemeter test
- intersection of elliptical zone of inhibition with strips that indicate MIC (tear shape of inhibition, the microbes are sad and crying)
"Death to the Microbes!!" Andrea, otherwise a cheerful person, but not to bad microbes.
-
Mechanisms of action for microbial drugs
- 1) Inhibitors of cell wall synthesis
- 2) Nucleic acid synthesis
- 3) Metabolic antagonists
- 4) Protein synthesis inhibitor
-
1) Inhibitors of cell wall synthesis
- Penicillin
- inhibits transpeptidase
- competitive inhibitor
- Semisynthetic Penicillin
- broader spectrum
- different side groups
- Cephalosporins
- used by most patients that are allergic to penicillin, structually and functionally similar
- Vancomycin
- Targets tetrapeptide linkages by physically binding to aminoacids and sterically blocking the glycosidic linkage and the peptidase.
-
2) Protein synthesis inhibitors
- aminoglycoside antibiotics
- cause misreading of mRNA by binding to the 30s ribosomal subunit, this is bacteriosidal
- Tetracyclines
- reversibly binds to the 30s ribsomal subunit. Inhibits binding of the aminoacyl-tRNA, bacteriostatic
- Macrolide
- inhibits translocation of tRNA by binding to the 23s rRNA of the 50s ribosomal subunit, somewhat bacteriostaic
- chloramphenicol
- inhibits peptidyl transferase reaction on 50s ribosomal subunit, bacteriostatic
-
3) metabolic antagonists
bind to essential enzymes for metabolic processes by competively inhibiting use of metabolites by key enzymes
- 1) Sulfonamides
- sulfur drugs, an analog for PABA (p-aminobenzoic acid) precurser to make folic acid
- 2) Trimethoprim
- Interferes with folic acid as well, it is a synthetic antibiotic
-
4) Nucleic acid synthesis inhibition
higher side effects, blocks either DNA replication or DNA transcription
- Quinolones
- bacteriosidal, targets gyrase, which is a topoisomerase
-
influencing factors of antimicrobial drugs
- Susceptibilty of pathogen to drug
- abiltiy of drug to reach:
- the site of infection
- Concentration in body that exceed pathogen MIC
Where + how + frequency of admin = speed of metabolism
-
drug resistance
- resistance can be transmitted
- mechanism is not confined to a single drug class
- resistant mutants arise spontaneously and are selected for
- Superbugs are resistant to multiple antibiotics
-
mechanisms of resistance
- 1) altered antibiotic target - mutation
- 2) antibiotic resistant genes (pick up plasmids)
- 3) antibiotic degrading enzyme
- 4) Antibiotic altering enzyme
- 5) Make pump to get out of cell
-
Origin and transmission of drug resistance
- 1) bacterial chromosomes
- 2) plasmids
- 3) transposons/integrons
-
Epidemiology of Disease
- Monitor public health data
- Respond to disease outbreak
- Investigate emerging and reemerging diseases
MMWR-Morbidity mortality weekly report
-
Types of disease
- Sporadic-occurs occasionally at irregular intervals
- Endemic-steady low level frequency at moderately regular intercal maintained
- Epidemic-sudden increase in frequency above expected number
- Pandemic-increase in disease occurrence within large population over wide region (usually worldwide)
-
Incidence versus prevalence
Morbidity versus mortality
Signs vs symptoms
#new vs #new+ongoing
#infected vs # deaths
Objective vs subjective changes
-
Course of infectious diseases
- 1) incubation period
- 2) prodromal stage
- 3) Illness
- 4) Convalescence
-
Surveillance methods
- Review of death certificates
- field investigation of epidemics
- investigation of actual cases
-
Remote Sensing and Geographic Information Systems
- RS-gathering of digital images of Earth's surface
- GIS-data management systen organizes/displays digital map data
-
Inf. Dis, Epi,
- Tries to determine:
- Causative agent
- source and or reservoir of agent
- mechanism of transmission
- host/environmental factors facilitating development of disease
- best control methods
- Correlation with single causative agent
-
Types of epidemics
- Common source epidemic (food/water)
- Propagated epidemic (like strep throat)
-
Herd Immunity
Resistance of population to infection/spread based on immunizations ~70% optimal
-
Infectious disease cycle
- 1) Pathogen
- Koch's Postulates
- 2) Source/Reservoir
- S-Source of transmission to host
- R-Normal location of pathogen
- 3) Transmission to host
- Airborne, contact, vehicle, vector-borne
- 4) Susceptibility of host
- 5) Exit from host
-
Transmission to host
- Airborne-Indirect (>1 meter) Direct (<1 meter)
- Contact-Direct (physical interaction), Indirect (intermediate usually inanimate-fomites), Droplet(large particles)
- Vehicle-Inanimate objects sometimes single vehicle pathogen to multiple hosts
- Vector-External (mechanical transmission-passive carriage of pathogen on body of vector and no growth of pathogen during transmission), Internal (carried within vector 1-harborage transmission: pathogen does not undergo changes within vector, 2-Biological transmission: pathogen undergoes changes within vector)
|
|