Exam 2 Flashcards
General steps a pathogen must perform to cause illness
- Exposure
- Adherence
- Invasion
- Colonization
- Toxicity, Spread or Death
Multidrug efflux system
Transport system used for pumping out drugs which enter the outer bacterial membrane
Basic exterior components of a bacteria
- Capsule
- Flagella
- Envelope
Bacterial capsule and biofilm
- Often polysaccharide
- Provides protection from host defenses, aids in attachment to host tissues or can have its own toxic effects
- BIOFILM: connected capsules that bacteria form when bacteria sense density of cohort as determined by pheromone strength
Bacterial envelope
Consists of inner membrane (peptidoglycans), cell wall (peptidoglycans) and [in case of gram negative bacteria] an outer membrane.
Difference between cell wall in Gram+ and Gram- bacteria
Gram+ bacteria have a thicker peptidoglycan layer, which includes teichoic and lipteichoic acids
Gram- bacteria have a thinner peptidoglycan layer, but also have near impereable outer membrane which contains LPS.
Mycoplasma
Cells which lack peptidoglycan, allowing them to squeeze through filters. They are insensitve to peptidoglycan attacks.
TIniest free-living organism known.
Wright’s Gremsa
Used to examine peripheral blood smears
What do acid fast stains stain?
Bacteria with cells walls containing long chain fatty acids
3 classes of Helminths
- Roundworms
- Flatworms
- Flukes
Roundworms
Type of Helminth
Aka Hookworms
- Collagenous tegument and non-segmented structure
- Larvae penetrate skin, are carried to lungs, go to mouth and are swallowed, and eventually reach the small intestine
Flatworms
Type of Helminth
Gutless worms, aka tapeworms
Flukes
Type of Helminths
Primitive leaflike worms with syncytial integument
Mechanisms of Bacteria Induced Injury (4)
- Bacterial Virulence
- Bacterial Adherence
- Endotoxin
- Exotoxins
Bacterial Virulence
Depends on ability of bacteria to adhere, invade, and deliver toxic moieties
Bacterial Adherens
- Adhesins are bacterial surface molecules that bind to host cells (ex. fimbriae or pili on surface of gram-negative bacteria)
- Entry into macrophages (directed b receptors that recognize antibodies or complement of surface of bacteria)
- Entry into epithelial cells (dependent on interactions between bacteria and receptors such as integrins)
Bacterial Endotoxin
LPS- structural componenet of out cell wall of gram negatives. Induces fever in host and activates macrohages/B cells
Bacterial Exotoxins
Toxis released by bacteria that interfere with cellular metabolism and allow bacteria to outgrow competing bacteria
Spectrum of inflammatory Responses to Infection
- Suppurative (Polymorphonuclear) Inflammation
- Mononuclear and Granulomatous Inflammation
- Cytopathic-Cytoproliferative Inflammation
- Necrotizing Inflammation
- Chronic Inflammation and Scarring
Supparative Inflammation + example
- Caused by pyogenic bacteria
- Increased vascular permeability
- Pus forming
ex. Pneumonia
Mononuclear/ Granulomatous Inflammation + example
Formation of giant cells
ex. syphilis
Cytopathic-cytoproliferative Inflammation + example
- Classic for virus mediated damage to host cell in absence of host inflammatory response
- Can result in:
- blisters (ex. herpes virus)
- lesions (ex. venereal warts/HPV)
- polykaryons (ex.measles)
- Inclusion bodies (CMV)
Necrotizing Inflammation+ example
- Uncontrolled viral infections
- Secreted bacterial toxins
- Cytolysis of host cells in protozoa infections (ex. group A streptococcus)
Chronic inflammation and scarring + example
Several inert organisms cause damage by the scarring process (ex. schistosome eggs)
What is the route of invasion for salmonella?
It enters the intestinal tract (after entering body orally), and ends up entering M cells of the Peyer’s patch.
Bacterial-mediated endocytosis and what is the key protein envolved?
Two-step process of (1) attachment and (2) entry, which involves the formation of large membrane ruffles and rearrangment of host cell cytoskeleton. Ruffles form as a result of Sip proteins which change the eukaryotic cytoskeleton to facilitate phagocytosis via ruffling.
How does s.typhimurium transition from intracellular infection to systemic?
After crossing the epithelium, it is engulfed by macrophages which carry it to the reticuloendothelial system and from there, into the bloodstream. It induces proteins to protect it while in the macrophage.
Key genes for pathogen facilitation of entry to M cell (what genes are involved and where are they?)
What do these genes encode for?
Many of the genes (including inv and spa) required for invasion are located on a 40-kB pathogenicity island called Salmonella Pathogencity Island 1 (SPI 1). They go to encode a type III secretory system used to export Sip proteins.
What keeps the phagosome with salmonella in it, from being fused to a lysosome
Type 3 secretory apparatus secretes proteins into M cell cytosol to inhibit fusion.
How does N. Gonorrhea avoid the immune system?
N. Gonorrhea is able to randomly change the appearance and composition of their adhesins (pili and non-fimbrial proteins), to protect themselves from being wiped out by host immunity.
Specific mechanism used by pathogen to facilitate entry into macrophages
Type III secretory system (pgrHIKL) exports proteins through bacterial cell surfce into the macrophage, therby facilitating phagocytosis.
General set-up of two-component signal transduction.
What autokinases are involved?
- Sensor (histidine autokinase): usually a membrane-bound receptor that autophosphorylates on a histidine reside. It uses ATP as its phosphor-donor.
- Response Regulator (aspartate autokinase): usually (but not always), a DNA binding protein that autophosphorylates using the phosphorylated sensor as its phosphor-donor. Response regulator is attached to an output domain (e.g. DNA-binding domain)
PhoP/PhoQ
Specific Two-component signaling system for Salmonella
- PhoQ is a membrane-bound histidine kinase sensor that senses low [Mg2+] (a sign that the salmonella has entered macrophage)
- PhoP is the response regulator associated with PhoQ. It functions as a DNA-binding protein and represses genes required for invasion into M cells and macrophages, while simultaneously activating genes required for survival in the macrophage.
- Specific gene deactivated by PhoP.
- Specfic gene activated by PhoP
- PhoP-repressed genes (prg)- genes needed for invasion of Mcell by salmonella
- PhoP-activated genes (pag)- essential for survival
Requirments and purpose for bacterial adherence
Purpose: defense against host’s mechanical cleansing
Requirement:
- Host cell surface receptor on cell which is typically a specific carbohydrate residue, which makes for easy attachment
- Bacterial adhesin which often a pili (attachment at a distance) or outer membrane protein (OMP) (intimate attachment)
Pilin Gene Organization and Mechanisms for Transportation
- pilE is the gene location expressed, due to a promotor
- pilS- silent genes due to being incomplete/ lacking a promoter
All of these genes have the same orientation and any gene moved to the pilE site becomes activated. This occurs via gene conversion or transformation.
- Gene conversion- occurs within a cell. PilS is an endogenote; donor is the actual cell which is going to recombine.
3 categories of “emerging pathogens”
- A previously unknown organism that causes disease
- A previouslt identified organism that has recently acquired the capacity to cause disease
- A previously identified pathogen that has recently acquired the capacity to resist antibiotic treatment
Reductionist approach of drug discovery
- Identify paradigms of drug discovery
- Design drugs to target virulence factors identified by experiment
Genomic approach of drug discovery
- Sequence the genome of the pathogen
- Design drugs to target all potential virulence factors (or potential vaccine targets)
What protective factors are included within the cell wall of Gram+ bacteria?
+ = teichoic acid and lipteichoic acid
LPS
Lipopolysaccharide
Aka endotoxin. Located within outer membrane of Gram-negative bacteria. It contributes to the structural integrity of the membrane and also protects from certain chemical attacks.
Key point about mycobacterial envelope
Mycobacterium have sugars on their cell surface which mimic host sugars. As a result, when they engage with macrophages they are uptaken and sequestered into safe intracellular compartments. These sugars also stimulate anti-inflammatory responses.
Prions (composition + diseases of association)
- Composed of modified host proteins
- Associated with neurodegnerative diseases
Commanilities between Chlamydiae, Rickettsiae, and Mycoplasms (4)
- Obligate intracellular pathogens
- Divide by binary fission
- Susceptible to antibiotics
- Lack certain cell structures
Best microscopy field to see spirochetes
Dark Field
Bacteria that looks like a tennis racket/ drum stick
Clostridium Tetani
- small rod with round terminal spores giving a drumstick appearance. Often isolated from deep wounds.
What are the speacial fungal stains? (4)
- Lactophenol cotton blue
- GMS
- PAS (periodic acid-Schiff)
- Mucicarmine (mucin)
Warthin-Storry or Steiner
Silver stains for bacteria and spirochetes
SIlver impregnanted stain for formalin fixed tissue
Best stains for parasites (4)
- Wright’s giemsa (blood smears)
- Wet mounts
- Trichrome
- Modified acid fast
What does calcofluor white stain?
Only the chitin/cellulose which is found (medically) in cell walls of fungus.
Key defense mechanism of clostridium perfringens
It produces enterotoxins (which is a class of exotoxins)
Type III Secretory Apparatus
- Complex multi-subunit structure involved in transporting virulence factors into host cells via direct injection. Tip of needle can partially penetrate the host cell, serving as a conduit.
- Gram-negative only
- Related to Flagella
The 3 steps of peptidoglycan synthesis
- Peptidoglcan subunits are synthesized in cytoplasm
- Subunits are transferred across the membrane by a carrier molecule
- Newly transferred subunits are cross-linked to the peptidoglycan which is already present on the other side of the membrane.
Main mechanism of penicillin function
Penicillin binding protein (PBP) makes and breaks the peptidoglycan cross-linking process. Penicillin inhibits these PBPs, thereby blocking peptidoglycan formation.
What is the step in bacterial nutrient breakdown just prior to fermentation/respiration?
Central Metabolic Pathway
It partially converts entering nutrients to energy just after the nutrients enter the cell.
Dangerous products of Aerobic Respiration and how they are cleared by bacteria.
Oxidative products (e.g. H2O2 and O2-)
Broken down via peroxides and superoxide dismutases, respectively.
Pathogens with Signficant Antigenic Variation (lots of different antigens within each class of pathogens) (7)
- Rhinoviruses (Colds)
- Influenza
- Gonorrhea
- Borrelia Hermsii (Relapsing fever)
- Borrelia burgdorferi (Lyme disease)
- Trypanosoma Bruvei (African Sleeping Sickness)
- Giardiasis
- Plasmodium falciparum (Severe malaria)
R plasmid (how is it generated, how is it replicated, what does it have and how does it evolve?)
“Resistance Plasmid”
- Is generated via transposition of a transposon into a conjugal plasmid
- Has several resistance genes and can evolve quickly via fusion to other plasmids
- Self replicating (unlike conjugal transposons which must intgegrate into chromosome to replicate)
- Conjugal plasmid (along with F plasmid)
F plasmid
Fertility Plasmid
Type of Conjugal plasmid (along with R plasmid). Can autonomously transfer themselves from one host to another.
The 4 main types of transposable elements
- Insertion sequences (IS)
- Transposons
- Transposable prophages
- Conjugal transpons
Insertion Sequences
Elements which only carry genes for transposition, including its own site-specific recombinase and 2 inverted terminal sequences
Transposon
Carry genes for transposition + another fxn (resistance, conjugation, etc.)
Transable Prophage
A bacteriaphage that is a transposon. It can alternate between lytic growth and lysogeny/
Conjugal Transposons
Jump from position to position within a given cell and also carry the machinery for conjugation, thus allowing them to mediate their own transfer to other cells (still as part of a genome though)
Conjugal R plasmids are also known as…
ResistanceTrasnfer Factor (RTF)
What is competance and what mediates it?
The ability of bacteria to take up DNA from the environment. Mediated by protein competence factor, which causes indiscriminate uptake of any DNA in the environment. It is also mediated by quorum sense.
2 simple steps for bacteriaphage infection
- Aduction (attachment)
- Injection of genome
Vibrio cholerae and bacteriophages
It is a bacteriophage!
In order to cause its toxic effect of cholera (and diphteria), the host bacterium must be infected by a phage (CTX phage) which comes from the vibrio cholerae virus.
Phages involved in lysogenic infection are aka…
Temperate phages
Operons
Unit of transcription that includes multiple cistrons (genes). Consists of promoter, operator, cistrons and terminator.
What does cAMP serve as a co-activator for?
It binds to the activator and increases its binding affinity
Sigma factor
A subunit of RNAP that specifically recognizes and binds the promoter
