Final: New material Flashcards
exotoxins
- produces and secreted by bacterium
- specific role in pathogenesis
- may act distant from bacterium
- our bodies produce antitoxin
endotoxin
- a part of the bacterial cell
- LPS
- acts systematically on host
hemolysins
red blood cells
leukocidins
white blood cells
what creates a channel in the membrane
hemolysins and leukocidins
what makes a lot of channels in the membrane
S. aureus and S. pyogenes
A-B subunit toxins
- toxins with two subunits
- toxin produced with subunits together
B subunit
binds cell surface
A subunit
active component
diphtheria toxin
- classic A-B subunit toxin
- transcribed, translated as a single gene unit
- post translational cleavage, reduction to active form performed by host cell
- B subunit binds to cell surface, endocytosed
- in acidic compartment, conformational change creates membrane pore, A subunit enters cytoplasm
- ADP ribosylation of EF-2
Super antigens
- toxins that bind to TCR and MHC activate immune system
- semi specific activation 3-30%
- results in massive overstimulation
medically important exotoxins
- botulinum
- tetanus
- cholera toxin
endotoxins
- LPS-lipopolysaccharide
- Lipid A portion is endotoxin
- released during cell death
- treatment w/ antibiotics may make this worse
- septic shock
- disseminated vascular clotting
- detect with limulus amoebocyte lysate assay
endotoxin induces…
fever and shock
- LPS released when bacteria are lysed in macrophage
- stimulated IL-1, tumor necrosis factor, other cytokines
genetics of pathogenicity
- mobile genetic elements contain toxin genes
- bacteriophage-lysogenic conversion
- plasmids
- transposons
- pathogenicity islands
plasmids and pathogens
toxin genes spread very rapidly
- virulence plasmids can be passed through the population
- tetanus toxin, staph. enterotoxins
lysogenic conversion
- bacteriophage can lyse their host or integrate into chromosome
- lysogens may carry virulence factor genes
- cholera toxin
- SEA
- diphtheria toxin
- botulinum toxin
pathogenicity islands
genomic elements containing virulence genes
- often id by different G+C content from rest of genome
- present in pathogenic strains, absent from avirulent
- potential horizontal transfer unclear
antimicrobial chemotherapy
- based on exploiting differences between our physiology and invading organisms
- antibiotic targets are enzymes or structures essential to pathogens success, but different from our essential parts
which microbe is hardest to treat?
viruses
- may essential parts to them are essential to us. makes it hard to make vaccine
which microbe is easiest to treat?
fungi? bacteria?
sources of antibiotics
natural compounds from bacteria (G+ rods), actinomycetes, fungi
example of a microbe that is very difficult to treat and needs specialized drugs
mycobacteria
bacteriostatic
inhibits growth
bacteriocidal
lyses cells
antibiotic resistance
- bacteria can develop resistance through several mechanisms
- destruction of the antibiotic (B-lactamase)
- mutations in the target site (alterations to ribosome)
- efflux pumps (pump antibiotics out of cells
beta-lactamases
- broad or narrow spectrum
- cleaves beta-lactamase ring
- very widespread in medically relevant bacteria
target alteration
- mutations in the target site that dont affect function
- affect binding of antibiotic
- if antibiotic action closely associated with target activity, more difficult
multi-drug efflux pump
- MDR bacteria a rapidly growing concern
- MDR-TB, MDR-pseudomonas
- one major mechanism is efflux pump
- can act on broad class of drugs
antibiotic resistance
- mutations may arise directly from selection pressure
- antibiotics come from natural sources
- organisms that make them are resistant to them
- organisms may compete by developing resistance
- genes for resistance spread by horizontal transfer
misuse of antibiotics
- Overprescription (colds, flus)
- use of weakened, outdated drugs
- failure to finish course
- unsupervised use
- long term use for sub-clinical infections
ramifications
- MRSA, VRE drug resistant nosocomial infections
- prophylaxis before surgery now requires harsher, higher doses of antibiotics
- gram-negative pathogens are almost always totally resistant B-lactams
- newer antibiotics are necessarily more costly, often have more side effects
filamentous fungi
growing as multinucleate, branching hyphae, forming a mycelium
yeasts fungi
growing as ovoid or spherical single cells multiply by budding and division
superficial mycoses fungi
- epidermophyton
- microsporum
- trichophyton
deep mycoses fungi
- aspergillus
- candida
- blastomyces
local fugal infections
- thrush
- tinea
systemic fungal infections
- cryptococcal meningitis
- aspergillosis
treatment options
- far fewer drugs
- ergosterol
(amphotericin B - binds ergosterol) - azoles (interfere with synth)
protozoa
- single celled
- intracellular and extracellular
- systemic infections
- immune evasion
insect borne protozoa
- leishmania - sand fly
- trypanosoma - chagas disease - reduviid bug
- African sleeping sickness - tsetse fly
- plasmodium - anopheles mosquito
ingestion of cysts
- systemic disease (toxoplasma)
- GI disease (amoebas, giardia, cryptosporidia)
treatment of cysts
- not many drugs options
- metronidazole
- immune evasion
- quinines and related for malaria
- resistance
helminths
- flatworms (tapeworms)
- flukes (schistosomes)
- roundworms (filarial worms)
routes of infection
- intermediate host (accidental ingestion)
- active skin penetration
- insect
- fecal-oral route
schistosomiasis
- affects 300-600 million people worldwide - blood fluke
- snail intermediate host
- other fluke infections (liver and lung)
- few available drugs
tapeworms
- adult form (intestinal tract)
- larval forms (intermediate host, disseminated tissue, cysts in brain, organs, varies by species)
roundworms-nematodes
- very diverse
- protective cuticle
- plant parasitic
- free living bacteriovorus
- pathogenic (person to person, arthropod vectors, zoonotic)
arthropods vectors of disease
- widespread
- many associations
- transmit many diseases
- plants, animals, humans
- control insects-control disease
herpesviridae
- often neurotropic
- causes various diseases (fever/genital herpes, chicken pox/shingles, infectious mono)
chicken pox/shingles
varicella zoster
- childhood CP
- adulthood shingles
- vaccines for both
papilloma virus
- HPV causes common warts, genital warts, cervical cancer
- very common
- HPV 6 and 11 cause genital warts
HIV
- human immunodeficiency virus
- a retrovirus
- RNA genome
- incorporates into host cell as cDNA
- infects CD4+ T-cells
Infection of Host Cells by
HIV
HIV surface glycoproteins bind CD4, CXCR4 molecules on T-cell
HIV latency andactivation
Provirus integrates into host cell genome, may be activated to produce virus particles
influenza
Influenza kills ~50k per year in
the US
Orthomyxovirus
Segmented genome
Surface antigens(spikes) hemagglutinin and neuraminidase
Large shifts in antigenic structure give rise to pandemics
antigenic drift and shift
- Drift-point mutations in
H,N antigens
Flu virus reassortment
leads to shift —Pandemic
strain
poxviridae
smallpox, cow pox viruses
Smallpox ~30% fatality rate
NOT chicken pox
(a herpes virus)
Double stranded DNA
Enveloped
smallpox (edward jenner)
Smallpox was a universal
disease
80% of Europeans
contracted it
30% mortality
Vaccine invented by
Jenner 1769
Based on cowpox (Vacca-
cow)
Last natural case in 1977
The black death
bubonic - fleas on rates
septicemic - in the bloodstream, results in septic shock
yersinia pestis
forms biofilm to block fleas digestive tract
- starving flea will now bite people
- c. elegans
SIR model of disease
Vaccine allows you to go
from Susceptible to
Recovered without passing
through Infected!
When S gets below 1/Ro,
that is when the epidemic
