Pathogens I Flashcards
What is salmonella
Salmonella enterica present in contaminated food - usually eggs, poultry, meat
And water
How many salmonella cases
40 000 cases reported every year - but underreported - should be 30x more
Vey common
Who does salmonella affect
Mainly young child’s, elderly, immunocompromsied ppl
400 annual deaths in us
Symptoms salmonella
Enteric fever (fever, headache, abdominal pain, transient diarrhea/constipation, infection causing respiratory, hepatic, spleen and/or neurological damage)=
Many consequences
Describe invasion of salmonella - gen
Comes in armed
Protects itself in endoscopes
Invasion depends on surviving endocytic pathway
Describe invasion of salmonella - step 1
Salmonella cells attach to intestinal epithelium - infect enterocytes by means of adhesins
Describe invasion of salmonella - step 2
Invasion fo bacteria follows and engulfment mediated by virulence factors
= get themselves phagocytosed- engulfed
Describe invasion of salmonella - step 3
Once inside cytoplasm- salmonella localized within a salmonella containing vacuole - scv (a converted endosome)
= where it replicates
Describe invasion of salmonella - step 4
Scvs transcytose to basolteral membrane and releases internal cells to the sub mucosa
What do bacteria lack
Internal membrane system comparable to secretory pathway of eukaryotic cells
What do bacteria have to compensate for their lack of internal membrane system
Instead = have specialized machinery to translocate proteins through their pm (2 membranes in case of gram neg bacteria)
Are secretion systems all different
Nooo
Some are common to all bacteria
Others are more elaborate
Describe elaborate secretion systems
Like secretion system 3 and 4 =
Can deliver protein through bacterial membranes
And ALSO through endosomal or plasma membrane of a euakaryotic cell
These more elaborate systems = found in only specific groups of bacteria - bacterial can inject proteins directly into cytoplasm of cell
Describe salmonella secretion system
Secretion system 3
- permits injection of proteins into the cytoplasm of enterocytes
Describe type 3 secretion system specifically
Looks like syringe
Cryo ‘em -
2 membranes with periplasmic space in between = can inject into pm
What do scv do
Incorporates into early endoscope pathway
What does salmonella bacterium encode for
Effector proteins that prevent scv from fusing to lysosome
Describe sopb
Maintains elevated and prolonged levels of pi3p
Prevents generation of pi(3,5)p2
What does scv acquire
Rab 6, connects to dynactin-dyenin machinery via rilp—> transported to perinuclear region
Describe sopd2
Removes rilp and prevents other rab 7 effectors (binds on late endosome) - from binding for further steps for lysosome function
Describe resulting scv
Has early and late endosome characteristics - arrests in late maturation stage
= keeps them from fusing with lysosomes so cannot harm salmonella
In general describe what scv does
Sopd2 displaces rilp/fyco1 = so late endosome doesn’t bind any motors = immobilized so blocks other effectors too (no hops, no fusing with late endosome/lysosome)
Describe legionella pneumophila bacteria
Likes to grow in monocytes and macrophages
Causes legionnaires disease
Can grow in water - like water tans
When inhaled = produces atypical pneumonia slow acting, atypical
(* First identified in 1976 in an outbreak of pneumonia at a hotel hosting the American Legion for a convention in Philadelphia.
* In this outbreak 182 people were infected and 29 died
* Source of the outbreak was traced to bacteria growing in a water tank associated with the air conditioning system)
legionella pneumophila bacteria Secretion system
Type 4 secretion system
Like type 3 - syringe = system can deliver proteins through pm of eukaryotic cell
Describe legionella pneumophila bacteria After phagocytosis
Type 4 secretion system injects a protein which causes rab6 to be ub —> and removed from endosomal membrane = but no recruiting rab7
Result = abnormal early endosome which cannot mature but can support bacterial growth (macrophage turned into bacterial incubator)
Describe other bacteria
Many other pathogenic bacteria use similar strategies to survive intracellularly but diff details (ex = m tuberculosis = prevents acidification of phagosomes)
Also secretion systems differ significantly between gram pos and gram neg bacteria
Some bacterial can also escape phagosoems/endosome and enter cytoplasm - these bacteria must target autophagy to survive = inhibit somethings here
Define virus
Protein/lipid particle that contains nucleic acid (dna or rna) that can self replicate but only inside a host cell - self replication produces new virus particles
(Do or sis dna or rna, also ones with single long strand nucleus acid, some with genomes that are segments)
What is virus dependent on
Host cell for protein synthesis
Viruses lack ribosomes and a complete set of tRNAs
But may have ability to modify host cell translation machinery
What can some but not all viruses do
Can replicated their own genetic material (true for any ssrna/dna viruses)
Other viruses - especially ones with dsdna genomes depend on host dna poly to replicate
Describe exs of diff viruses - gen
Variety of diff structures
Rhinovirus + adenovirus = colds, non envelop
Describe types of viruses - gen
Both dna and rna vrisues, can have very diverse forms
Whether they have envelope affects strongly how they enter and how they are released from cells
Bacteria = own complete prokaryotic organism
Adenovirus = resistance, can survive in to 15 mins in 70% ethanol
Name exs of diseases caused by viruses
- Classical childhood diseases (polio, measles, rubella, mumps etc). Usually prevented with vaccines.
- HIV infection (currently no effective vaccine)
- Respiratory infections (influenza, common cold, COVID). Multiple viruses cause the common cold including, among others, rhinoviruses (most frequent), coronaviruses, adenoviruses and influenza viruses.
- Insect-transmitted diseases (Zika, yellow fever, dengue)
- This list is very far from complete (even for the categories listed)
Describe kinds of viruses - by envelopes
Eneveloped= one membrane
Non enveloped = no
Complex = multiple membranes
Non enveloped virus - genome
Can have any kind of genome
Non enveloped virus - virus particle
Virus particle consists of protein complexed with nucleic acid
Non enveloped virus - enters cell how
Often enters cell by endocytosis - assembled in cytoplasm
Non enveloped virus - release of new particles
Release of new virus particles may require cell to lyse
So more cells cannot be infected until first cell dies
But some viruses - polio and related vrisues = have found alternatives
Non enveloped virus - exs
Reoviruses - dsrna, adenovirus - dsdna, poliovirus = (+)-ssrna, t4 bacteriophage
Describe (+)-ssrna
Functions as message directly = if viral rna gets into cytoplasm = has ribosome binding site and can directly start to produce proteins
tRNA directed pol = onlu getting ssrna into cell = sufficient to start viral infection
Describe polio and related vrisues
NON EVENLOPED
Crystalline regular structure = precise geometry, symmetric, rna inside
Ssrna
Poliovirus = 4 subtypes, aa inside, hi infected = and can affect neurons - acute paralysis
Rhinovirus = many kinds so hard to treat
enveloped virus - genome
Can have any kind of genome
enveloped virus - Virus particle
Lipid bilayer as envelope
Normally derived from cellular membranes - of host cells
Can be destroyed by detergent
enveloped virus - internal part
Internal part = within envelope consists of protein complexed with Nucleic acids
enveloped virus - integral membrane proteinn
Integral membrane proteins cross envelop
May recognize receptor proteins on target cell and can permit direct fusion of the virus with the cells membrane or fusion after endocytosis (sometimes lipid bilayer fuses with membrane)
(Tm envelope protein binds to protein on surface of target cell = binding needed for virus to ifnect)
enveloped virus - Exs
Influenza virus (-)-strand ssrna
SARS cov 2 (+)-strand rna (if wash hands = kill it bc inactivates membrane)
HIV - retrovirus with rna genome
Herpes virus - dna virus
Also very susceptible to inactivation with alcohol
Describe sars cov 2 - image
em micrograph
See lipid bilayer
Negative stain ‘em - excludes stain
Sees huge spikes
Describe sars cov 2 - all parts
Nucleocapsid = genomic rna bound to this
Envelope small membrane protein = allows ions to cross membrane - ion channels important for cells
Spike glycoprotein = ab here = will neutralize, complement ssstem
— has ace2 binding site
- binds ace2 receptor on target cells
If change ace2 binding site - diff aas = why so many variants
Membrane protein
Describe sars cov 2 - integral membrane protein
M = membrane protein
S = spike glycoprotein
E = envelope small membrane protein
Describe ex of complex virus
Pox virus
Describe pox virus structure
Pox virus has 2 envelopes and a complex structure so my subsequent statements about enveloped viruses may not apply
Describe pox virusEs in humans
Include small pox virus and vaccina virus (used as vaccine against smallpox - extinct)
Some others = monkey pox, cowpox
Infrequently infect humans
Describe pox virus And some other very large vrisues
Overlap with the smallest bacteria but differ in lacking the means (ribosomes) to synthesize their own proteins - do not have machinery, very compelx, have many genes
Describe pox virus - ex vaccina virus
Vaccina virus = Virus used in small pox vaccine
How to treat bacterial diseases
Antibiotics have been avialable to treat bacteria diseases for decades
Possible to take advance of differences in biochemistry between prokaryotes and eukaryotes
Almost all bacteria susceptible to some antibiotics
(Many bacteria have proteoglycans - not found in our cells)
Describe antiviral drugs
Only developed recently and only for a few vrisues
Viruses extensively use host cell machinery
Ex =
HIV = reverse trans riptide can be inhibited
SARS cov 2 = rna directed rna pol = can be inhibited
Describe vaccines against bacteria or vrisues
Must be devised one organism at a time
Vaccine development against a few viruses = difficult, also virus can mutate v easy
Describe entire life cycle of virus
Entry into cell
Duplication of genetic material ad alterations to host cell (to cytoplasm or nucleus sometimes) - may include construction of virus factories
Production of new virus particles
New virus particles leave cell
Describe early phase for many vrisues
Duplication of genetic material and alterations to host cell - replicate and modify cells
Describe late phase of many viruses
Production fo new virus particles
Describe virus factories
Extensive modifications of internal membranes in cell
