Flashcards in Host-Parasite Interaction Deck (41):
benefit microbe, harmless to the host
mutual benefit to both and microbe
benefit to the microbe, harm to the host
- in order for a microbe to be pathogenic, it must enter the host, maintain a population, and cause damage to the host.
Type I secretion
- Enterohemorrhagic E. Coli
Type II secretion
- Vibrio cholera
Type III secretion
- Enteropathogenic E. Coli
Type IV secretion
- Agrobacterium tumefacians
- sometimes interactions are specific, sometimes not
- N. gonorrhea
- Opa protein binds receptors in urogenital epithelium
- fimbriae bind to epithelium of small intestine
- help streptococcus mutant bind to tooth surfaces
- made up of LPS
- the presence of LPS in an animal is always indicative of an infection, and the innate immune system will kick in any time LPS is detected (pyrogenicity)
- specifically made by the microbe in response to host invasion
- exported from the cell and have specific targets in or on the host cells.
types of exotoxins
- cause damage to host cell structure and activities
- protein synthesis inhibitors - diphtheria toxin
- hemolysins - attack RBC
- leukocidin - attack WBC
- do so by inserting pore forming proteins into target cell membranes
- cause damage to neural tissues and disrupt nerve conduction
- botulism toxin - prevents release of acetyl choline which prevents muscle contraction
- tetanus toxin - blocks release of gaba which prevents muscle relaxation
- mainly act on tissues in intestines
- cholera toxin - massive diarrhea and water loss
- A subunit is the toxin
- B subunit binds to the host cell
How AB toxin works
- B subunit (bound to A) will recognize a receptor on the host cell surface and bind to it.
- The host cell will be signaled to take up the bound AB toxin via endocytosis.
- upon entry, the A and B will dissociate and the toxin will interact with the target
- many but not all are enzymes called ADP ribosyltransferases, which transfer the ADP-ribose from a NAD nucleotide to its target protein
- once target protein has been ADP ribosylated, it becomes inactive
targets of ADP-ribosylation
- elongation factor 2 - diphtheria toxin
- adenylate cyclase - cholera, pertussis toxin
- G-actin - clostridium toxA
Toxin Delivery (Secretion Systems)
- The type I-IV secretion systems are used by Gram-negative bacteria to get virulence factors past both membrane and out of the cell.
- I and II deliver the secreted protein into the environment around the cell, but are not specific for toxin delivery.
- III and IV deliver the toxins directly into the cytoplasm of host cells.
Type I secretion system
- consists of an outer membrane channel
- always TolC
- and an inner membrane ABC transporter
- depends on the protein
- each protein requires a unique ABC transporter
- identified by the presence of a protein motif called ATP Binding Casette
- casette binds and hydrolyzes ATP, providing energy to transport the protein.
- the rest of the transporter specific for the protein being transported.
E. Coli O157:H7 secretion system
- causes hemolytic uremic syndrome
- the disease is caused by production of hemolysin secreted by type I secretion
- lysed blood cells clog glomerulus in kidneys and waste products accumulate in the blood
- bacteria almost never found in the blood.
- hemolysin is secreted as a monomer but assembles as an oligomer in the RBC membrane, and then insert as an octomer into and through the membrane.
Type II secretion
- method of getting proteins past the outer membrane, but proteins secreted must be in the periplasm to begin with.
- use Sec system to transport proteins into the periplasm
- once in periplasm, push protein past outer membrane by type II
- homology to type IV pilus
Cholera toxin secretion system
- when large numbers of it are ingested, they will make and secrete the cholera toxin. Outbreaks correlated to the sea surface temperatures
- since 1817 there have been 7 (or *) major pandemics
- AB toxin that is active against the epithelial cells of the intestines
- once inside cell, A subunit will modify adenylate (through ribosylation) to make it always activated
- increases cAMP levels which triggers massive losses fluid, severe diarrhea, dehydrates, and could result in death (from hypovolemic shock)
Type III secretion
- they deliver the toxin directly to the cytoplasm of the host cell.
- The TTSS passes through three membranes.
Enteropathogenic E. Coli secretion system (EPEC)
- first attaches to host cell via fimbriae and protein intimin
- once cell close enough the use the TTSS, the Tir proteins are injected
- TSSS will inject toxin identified as EspF
- serve as attachment sites for EPEC as well as nucleation sites for actin polymerization.
- actin pushes the host cell membrane up, creating the pedestal on which EPEC will sit on.
- basically make their own adherence molecule.
- directed to the mitochondria and causes leaks
- mitochondria release cytochrome C which signal signal apoptosis.
- epithelial death causes breakdown of mucosal barrier and diarrhea
Type IV secretion
- powered by ATP, also resembles type IV pili (conjugatation pilus)
- directly inject DNA and protein into the cell.
- transport occurs all the way from the cytoplasm of the bacteria to the cytoplasm of the host
Agrobacterium tumefaciens secretion system
- a gall (plant cancer) caused by insertion of proteins and oncogenic DNA via a type IV secretion apparatus
- bacteria capable of causing the tumors contain a tumor inducing plasmid (Ti) plasmid
- must enter through a wound
- contains a small portion of DNA (T-DNA) that is transferred to the plant to cause the tumor, the opine permeate and opine catabolism proteins, and Vir proteins.
- contains genes that encode a type 4 secretion system that will transfer T-DNA and the VirD2.
- site-specific DNA recombinase that will help transport the T-DNA into the nucleus and insert it directly into the plant chromosome.
- contains genes that will make the plant produce auxins (plant hormones) and cytokines, plant steroids that will cause the cell to reproduce rapidly and form the gall.
- also present are the genes that cause the plant to produce opines and nopaline.
- rare amino acids that will be excreted by the plant cells to feed the bacteria.
- argenine and lysine residues lined up
- A. tumefaciens use the opines as food, but only if they are carrying the Ti plasmid, as it contains the genes required for opine catabolism.
- bacteria that do not have the plasmid do not have the ability to break down opines.