Week 4 Flashcards
Name the major types of antimicrobials that affect cell wall synthesis
Beta lactams
other antimicrobials such as Vancomycin and bacitracin and daptomycin
What are the 6 classes of B-lactam antibiotics?
Natural Penicillins
Amino penicillins
Penicillinase-resistant penicillins
Anti-pseudonomal penicillins
Cephalosporins
Carapenems
Name 11 penicillins
Amoxicillin Ampicillin Dicloxacillin Indanyl carbenicillin Nafcillin Methicillin Ticarcillin Oxacillin Piperacillin Penicillin G Penicillin v-K
How many generations exist for cephalosporins?
5
Name two antimicrobials in the first cephalosporin generation
Cefazolin
Cephalexin
Name three cephalosporins in the second generation
Cefaclor
Cefuroxime
Cefoxitin
Name four cephalosporins in the third generation
Cefdinir
Cefotaxmine
Ceftazidime
Ceftriaxone
Name one antimicrobial of the fourth cephalosporin generation
Cefepime
Name one antimicrobial of the fifth cephalosporin generation
Ceftavoline
Name three antimicrobials of the carbapenems
Ertapenem
Imipenem
Meropenem
Name one monobactam antimibrobial
Aztreonam
Name three B-lactam inhibitors
Clavulanic acid
Sulbactam
Tazobactam
Describe how B-lactam drugs work
They target the transpeptidase enzyme* (penicillin-binding protein) which is located on the bacteria’s cytoplasmic membrane
What does transpeptidase PBP enzyme do in bacteria?
This enzyme carries out the last step of peptidoglycan wall synthesis by creating transpeptide links in between the peptidoglycan chains
Are B-lactam antimicrobials bacteriocidal or bacteriostatic? Why?
They are bacterocidal because it will cause the peptiglycan walls to fail, causing the bacteria to lyse due to osmotic forces
Are b-lactam drugs more effective against actively proliferating microbes or slowly proliferating microbes? Why?
Actively proliferating, because they inhibits cell wall SYNTHESIS
Why are B-lactams ineffective against mycoplasms?
These bacteria have no cell wall
How should you prescribe doses for B-lactams?
Since they are type 2 (time dependent), you want o keep their serum concentrations above MIC at least 50% of the time
True or false.. natural penicillins are highly susceptible to bacterial b-lactamases
True
Name two natural penicillins
Penicillin G Penicillin V (VK)
Natural penicillins have the highest activity against gram ___ organisms
Positive
Another name for aminopenicillins is ____
Extended spectrum penicillin
Name two aminopenicillins
Ampicillin
Amoxicillin
True or false… aminopenicillins re resistant to B-lactamases
False. However, they are less susceptible than natural penicillins
Another name for penicillinase-resistant penicillins is ____
Anti-staphylococcus penicillin
Name four penicllinase-resistant penicillins
NAFCILLIN*
Methicillin
Oxacillin
Dicloxacicillin
True or false.. penicillinase-resistant penicillins are relatively resistant to B-lactamases
True
Penicillinase-resistant penicillins have lower activity against gram ____ organism and inactivity against gram ___ organisms. However, they are active against ____
Positive
Negative
Staphylococcus aureus
____ is used to treat staphylococcal infections (but not MRSA). ____ is used as a first-line treatment of choice against staphylococcal endocarditis
Nafcillin
Nafcillin
Of all the anti-pseudomonal penicillins, which two antimicrobials have the broadest spectrums of activity?
Ticarcillin
Piperacillin
Monobactams are a type of ____. They have strong activity against susceptible gram ___ organisms
Anti-pseudonomal penicillin
Negative
Ureidopenicllins, such as ____, are a subclass of anti-pseudonomal penicillins. They are active against ____
Piperacillin
Pseudomonas and gram - rods
Cephalosporins are ____ so long as T>MIC is maintained properly
Bactericidal
What class of antimicrobial has the broadest antibacterial effect?
Carbapenems (specifically imipenem)
What is the only true naturally occurring penicillin?
Penicillin G
Penicillin G is _____ hydrolyzed by penicillinase enzymes (B-lactamase)
Rapidly
How is penicillin G usually administered?
IM or IV
True or false… penicillin G is good at penetrating the CNS and has a long half life
Both statements are false
What is the difference between penicillin G and penicillin V?
Penicillin V is acid stable, meaning that you can take it orally instead of IM/IV
It has the same Gram + activity but less gram - than G
What is the advantage that aminopenicillins have over natural penicillins?
They are extended spectrum penicillins, meaning that they have better gram - coverage
Aminopenicillins are the drugs of choice for what three things?
Prophylaxis of infective endocarditis*
Listeria monocytogenes
Treatment of UTIs causes by susceptible enterococci
Aminopenicillins are usually administered with ___ such as ___, ___, or ____.
B-lactamase inhibitors
Clavulunate acid
Salbactam
Tazobactam
What is augmentin? What is unasyn?
Augmentin - amoxicillin + clavulanate
Unasyn - ampicillin + sublactam
Amoxicillin has a ___ oral absorption, ____ Cpmax, ___half life, and ___ likely to cause adverse GI effects than ampicillin
Higher
Higher
Longer
Less
A drawback to amoxicillin is that it can inhibit renal excretion of ___
Methotrexate
The drug of choice for prophylactic prevention of endocarditis is ___. If the patient is allergic to this drug, they may take ___ instead. If that still doesn’t work, then you could prescribe ___, ___, or ____.
Amoxicillin
Cephalexin
Clindamycin
Azithromycin
Clarithromycin
Which is better absorbed orally, ampicillin or amoxicillin?
Amoxicillin
It is also not affected by the presence of food when ingesting.
What is an adverse effect of ampicillin?
Could lead to a superinfection of C. Dificile. —pseudomembranous colitis
____ can inactivate ampicillin if mixed
Hydrocortisone
True or false… ampicillins dampen the effect of oral contraceptives
True
Parents often give their sick children ampicillin because why?
It is in the form of a liquid (the pink bubble gum medicine), so young children can take it
Which penicillinase-resistant penicillin is discontinued in the U.S because it made the glomerulus in the kidney ineffective?
Methicillin
True or false.. penicillinase-resistant penicillins are more potent than penicillin G
False, it is less potent
True or false… nafcillin can be used to treat MRSA
False.. although it is excellent at treating staphylococcal infections, it cannot treat MRSA
Naf for staph!
What do probenecids do? How do they do it?
The slow renal excretion to retain serum levels of penicillins, cephalosporins, monobactams, and imipenems. Also used to treat gout
They do this by inhibiting organic ion transporters (OATs) in the kidney
Why is it that probenecid does not affect the concentrations of nafcillin, oxacillin, and dicloxacillin?
These drugs are lipophilic and undergo biliary excretion (through gall bladder, not kidney)
Anti-pseudonomal penicillins are used for ….
Treating serious bacteremia and UTIs due to bacteria resistant to Pen G and ampicillin
Administer IM or IV, NOT PO
Carboxypenicillins are subclass of ____. Two carboxypenicillins are ___ and ____
Anti-pseudomonas penicillins
Indanyl carbenicillin
Ticarcillin
Indanyl carbenicillin is ___ active and used clinically for management of organisms resistant to ___
Orally
Ampicillin
Ticarcillin is ___ active than indanyl carbenicillin. It is used for targeting gram ___ bacteria, particularly ____
More
Negative
P. Aeruginosa
What antibiotic would most likely be given to a patient with an infection of a urinary catheter?
Ticarcillin
____ is the broadest spectrum of the antipseudonomal penicillins
Piperacillin
Aztreonam is great for patients with ___ mediated penicillin allergy
IgE
True or false… if you are allergic to penicillin, you are most likely allergic to all other B-lactams
True
Large doses of pen G can produce what symptoms?
Lethargy, confusion, twitching, seizures, kidney failure, coma
Broad spectrum drugs are more likely to result in a super infection. Pseudomembranous colitis can result to taking what 4 drugs?
Piperacillin
Cephalosporins
Aztreonam
Aminopenicillins
How are cephalosporins excreted from the body?
Renally
Depending on the generation, cephalosporins are moderate to broad spectrum. Are they all bacterocidal or bacterostatic?
Bacterocidal
As you increase in cephalosporin generation, it is more targeted towards gram ____, and its B-lactam resistance ____
Negative
Increases
Which generation of cephalosporin is active against MRSA?
5th
True or false.. the first generation cephalosporin penetrates the CNS. It is the first drug of choice when treating any active infection
Both statements are false
_____ is used for prophylaxis prior to surgery
Cefazolin (first generation cephalosporin)
Cefaclor (a second generation cephalosporin) is used to treat ___
Sinusitis and otitis due to H. Influenzae
Cefuroxime is unique in that it can…
Cross the blood brain barrier
Name some features of third generation cephalosporins
Very effective against gram - rods
Most can cross blood brain barrier
Which third generation cephalosporin is active against pseudomonas aeruginosa?
Ceftazidime
true or false.. cefepime is active in treating MRSA
False.. that is a fourth generation cephalosporin
Ceftaroline (5th generation) is active against MRSA
What drug has the broadest spectrum coverage available to man?
Imipenem , a carbapenem
True or false… carbapenems are very stabl in the presence of B-lactamases
True
Name 2 non-B-lactam antibacterials that affect cell wall synthesis
Bacitracin (topical)
-against + and -
Vancomycin
-used to treat endocarditis in penicillin-allergic patients
True or false vancomycin active against gram + and groom - bacteira
False… just gram +
What makes vancomycin unique?
It inhibits cell wall synthesis at an earlier point than B-lactams
Poorly absorbed orally
Can cause red man syndrome - rapid infusion induced non-immunological release of histamine
Name 2 non-b-lactam antibacterials that affect the cell MEMBRANE
Polymyxins - detergent that disrupts membranes. Effective against gram -
Daptomycin - effective against gram + . Alters cell membranes electrical charge
How does daptomycin work?
Throws off K gradient by inserting a K pore.
Daptomycin is inserted with calcium dependence.
Rhabdyomyolosis is an adverse effect of daptomycin. What is it?
Muscle pain
Describe the progression of symptoms of anaphylaxis
Skin
Eyes/nose/gi
Respiratory
Cardiovascular
What are the three types of allergic reactions to penicillins/B-lactams?
Immediat/acute onset - reactions within 30 minutes, life threatening
Accelerated onset - arise within 30min to 48 hrs after administration. Non life threatening
Delayed onset - longer than two days after administration. Most adverse reactions to penicillin are of this type (mild rashes)
Bacteria that are able to take up DNA are said to be ____
Competent
True or false… most competent bacteria only take up linear DNA through transformation, not plasmids or viral DNA
True
What is the difference between generalized and specialized transduction?
Generalized - if the virus inserts its DNA randomly into the bacterial DNA
Specialized - if the virus enters into the bacterial DNA in a specific site
What does the F plasmid code for?
A type four sex pilus
These plasmids contain TRA genes, which allow the plasmid to transfer.
What are col plasmids?
Contain genes that code for bacteriocins (proteins that can kill other bacteria). Some are also toxic to host cells (genotoxins)
What are virulence plasmids?
Encode virulence factors. These can make a harmless bacterium into a pathogen
What are R plasmids?
Resistance plasmids. These contain genes that provide resistance against antibiotics or poisons
Some plasmids can only be transferred during conjugation if they tag along with other plasmids that contain ___
Tra genes
True or false… R plasmids typically code for one resistance gene
False. They can cary many
What is the difference between direct transposition and replicative transposition?
Direct transpotion is like cut and paste of a transposable element
Replicative transposition is like copy and paste of a transposable element
What are pathogenicity islands?
These are condensed segments in the bacterial DNA that house many of the virulence genes
This means that horizontal gene transfer can result in almost immediate virulent strains
Commensal E. Coli, if given virulent genes via horizontal gene transfer can become pathogenic. One pathogenic strain is called ___ which causes URIs.
Uropathogenic E.coli
Does the number of bacteria and diversity of bacteria increase or decrease as you descend the GI tract?
Increase
What are some good things that our gut microbiota does for us?
Helps us extract energy from food
Required for proper immune system development
Affects metabolism of drugs
Protects against pathogens
Clostridium difficile is gram ___ and found in low abundance in the GI tract of 5% of humans. It only causes pathogenesis following antibiotic treatment, if so, it may cause ____, which is …
Positive
Pseudomembranous colitis - sever ulceration of the colon
Clostridium difficile causes what three symptoms? Why is it that C. Difficile can survive antibiotics? (3 things)
Diarrhea
Abdominal pain
Fever
Resistance genes and mutations
Biofilm formation
Spore formation*
Why is it significant that clostridium can produce spores?
The infective spores persist in harsh environments and are hard to kill. They can remain dormant for long periods of time
What stimulates the formation of spores by clostridium difficile?
Spores form when there is shortage of nutrients
Antibiotics can stimulate spore formation
Any other harsh environment in which the bacteria thinks it will die in
Spores have multi-layered protective coats consisting of what five things?
Cell membrane Thick peptidoglycan mesh Another cell membrane Wall of keratin-like protein Outer layer (exosporium)
True or false… most antibiotics and hand sanitizers can kill spores
False
What two genera produce spores?
Clostridium (anaerobic G+)
Bacillus (aerobic G+)
What is a nosocomial infection?
Hospitally acquired
What bacteria spores are likely to be found in the hospital, environment, gas gangrene, and food?
Hospital - C. Difficile
Environment - c. Tetani, B. Anthracis
Gas gangrene - C. Perfringens
Food - C. Botulinum, C. Perfringens, B. Cereus
Once a bacterial cell is phagocytosed, the phagosome will fuse with a lysosome to form a ___
Phagolysosome
What are three methods bacteria use to evade host defenses?
Some avoid uptake by phagocytes
Some primarily reside within host cells
Some alter their virulence factors and can live in or out of cells (facultative intracellular bacteria)
What are survival strategies that bacteira use in the extracellular environment?
Production of capsules
Varying of surface exposed antigens (antigenic variation, phase shifting)
Secretion molecules that interfere with host defenses (toxins that modify host cells, enzymes that destroy defenses)
What are some things bacteria do to survive within host cells?
Developed resistance to reactive oxygen species (by possessing superoxide dismutase) and NO (by suppression of host NO synthase expression)
Neutralize phagolysosome contents
Prevention of phagolysosome fusion
Escape from phagosome
What bacterial genera prevent phagolysosome fusion?
Mycobacterium
Legionella
What bacterial genera escape from the phagosome?
Listeria, francisella, rickettsia
Listeria monocytogenes is a gram ___, ____ ____. Causes listeriosis (foodborne pathogen). It is a master escape artist because it is able to use its internalins ___ and ___ to engage ___ and trigger actin reorganization of the host cell. This will allow internalization of the bacteira by the host cell
Positive, facultative anaerobe
InlA and InlB
Surface receptors
How does listeria monocytogenes move around within host cells?
Actin-based intracellular bacterial mobility (“actin rockets”)
This will also allow them to spread laterally from cell to cell within tissue
True or false… in order to be considered toxins, they must be secreted from bacteria
False
Name some things that virulence factors can do
Cause aberrant activation of host inflammatory response (lipid A*)
Bind and act at host cell surface (super antigen)
Act on host cell membranes (forming pores)
A-B type toxins, includes single chain and multisubunit toxins
What are some things that the bordetella tracheal cytotoxin does?
Stimulates Nod1. Arrests ciliary movement, causes extrusion of ciliated cells
Coughing
Secondary infections
Describe mycobacterium ulcer as polypeptide-derived mycolactone
Causes apoptosis/necrosis of host tissue without pain
Buruli ulcers
What do exotoxins like superantigens do?
Forces APC and T cell together by binding to MHC2. This will cause lots of cytokines to be released and a hyperinflammatory response. This also exhausts and kills T cells
What are some things that staphylococcus aureus causes?
Food poisoning
Bacteremia
Toxic shock syndrome
Abscesses and cellulitis
Many of the virulence factors encoded by S. Aureus are regulated by ___
Quorum sensing
Prokaryotic ribosomes are made up of ___ and ___ subunits to total ____ whereas eukaryotic ribosomes are made up of ___ and ___ subunits to total ____
30s + 50s = 70s
40s + 60s = 80s
What are the three big targets of the drugs that disrupt protein synthesis?
50s subunit
30s subunit
TRNA synthetase
What are the three ribosomal binding sites and what are their functions?
A site = holds amino acids to be added
P site = holds growing polypeptide chain
E site = exit site for tRNA
True or false… human mitochondrial ribosomes highly resemble bacterial ribosomes. How is this important with dosing?
True
At high doses, selectivity is reduced and toxicity increases
What are the main differences between prokaryotic mRNA and eukaryotic mRNA?
Prokaryotic mRNA is polycistronic and its life span is short because it is unstable
Eukaryotic mRNA is monocistronic and its lifespan is long because it is quite stable
What does chloramphenicol do?
Binds to 50s subunits and inhibits the formation of the peptide bond
What does streptomycin (aminoglycoside) do?
Changes shape of 30s subunit, causes code on mRNA to be read incorrectly
What does erythromycin (macrolide) do?
Binds to 50s subunit and prevents translocation - movement of ribosome along mRNA
What do tetracyclines do?
Interfere with attachment of tRNA to mRNA-ribosome complex
Name 5 aminoglycosides
Gentamycin Neomycin Amikacin Tobramycin Streptomycin
Aminoglycosides bind to the ___ subunit, changing its ____. What are three consequences of this?
30s
Shape
Blocked initiation
Premature termination
Misreading of mRNA
Which aminoglycoside is the oldest of the family and has the highest level of bacterial resistance? How is it administered?
Streptomycin (IM, IV)
What aminoglycoside is the most commonly prescribed aminoglycoside and is often used in combination with penicillins? How is this drug administered?
Gentamycin (IV)
Which aminoglycoside drug has the broadest spectrum of all aminoglycosides? How is it administered? This is often used for fighting nosocomial infections
Amikacin (IM IV)
Which aminoglycoside drug has excellent activity against pseudomonas aeruginosa? How is it administered?
Tobramycin (IM, IV)
Which aminoglycoside drug is used topically only?
Neomycin
What is a neomycin enema?
This is used to flush and detoxify the colon and lower bowel before bowel surgery. Note that this drug is flushed out before it is absorbed
Aminoglycosides are primarily used to treat infections caused by ___, gram ___ bacteria
Aerobic
Negative
Are aminoglycosides bactericidal or bacterostatic? How often should these drugs be taken?
Bacterocidal
These are concentration-dependent killing (type 1) but also have some mild post administration effects.
They should be taken daily. They should be taken every 8 hours if you are pregnant, its a neonatal infection, or if it is bacterial endocarditis
True or false… aminoglycosides may be taken orally
False
Why must neomycin be used topically only?
It has high nephrotoxicity
In anuric patients, half life can ___ by 20x-40x. Why is this significant?
Increase
This is significant because aminoglycosides are excreted renally. If they have impaired renal activity, caution should be taken because these drugs’ toxicity is concentration dependent
Aminoglycosides have a syngestic relationship with ___ or ___
B-lactams
Vancomycin
These drugs break down the cell wall so that the aminoglycosides can get into the bacteria to mess up their protein production
What are four adverse effects of aminoglycosides? Describe them
Ototoxicity - inner ear damage. Toxicity correlates with the number of destroyed hairs
Nephrotoxicity - kidney damage. Thus, frequent plasma concentration monitoring is essential
Neuromuscular paralysis - decrease ACH postsynaptic sensitivity. Patients with myasthenia gravis at greatest risk. Accumulation in fetal and plasma (teratogenic-so avoid in pregnancy)
Contact dermatitis - common reaction to topical neomycin
What four groups are at the most risk for aminoglycoside adverse effects?
Elderly (reduced kidney function and reduced ear hair cells)
Impaired renal function patients
Septic patients
Patients with previous exposure to aminoglycisides - can result in functional accumulation (post antibiotic effect)
Name four tetracyclines
Tetracycline
Doxycycline
Minocycline
Tigecycline
Are tetracyclines typically broad spectrum or narrow spectrum?
Broad spectrum. Active against gram + and - and atypical intracellular organisms
Tetracyclines bind ____ to the ____ ribosomal subunit which will…
Reversibly
30s
Prevents attachment of the aminoacyl tRNA
Are tetracyclines bacterocidal or bacterostatic?
Bacterostatic
What class of drugs are often used to treat acne vulgaris?
Tetracycline
True or false… if bacteria are resistant to one tetracycline, they are resistant to ALL tetracyclines
False. Although they are resistant to most, tigecycline is usually still effective
True or false… tetracyclines should be taken orally with food
False. Although they can be taken orally, oral absorption is altered by diary, iron supplements, or antacids
Tetracycline concentrates where?
In calcium-hydroxyapatite teeth/bones, or in tumors with high calcium content
Name 10 non-oral adverse effects to tetracyclines
***Disulfiram-like effect (hangover) (avoid alcohol)
GI upset, hepatotoxicity, headache, metallic taste, PHOTOTOXICITY, vestibular problems, benign intracranial hypertension, itching in anal and genital areas, super Infections of candida and **clostridium difficile (pseudomembranous colitis)
True or false… tetracyclines are safe to give to pregnant patients?
False!!!
Name two oral adverse effects of tetracycline
Hairy tongue - due to defective desquamation of the filiform papillae
Deposition in bone and primary dentition - causes discoloration and hypoplasia of developing teeth.
Contraindicated in pregnant patients, breast feeding patients, and in children younger than 8 years, and in patients with liver and renal disease
Tigecycline has the same spectrum as other tetracyclines, plus it has activity against….
MRSA
Multi-drug resistant S.pneumoniae
Vancomycin resistant enterococci
Some anaerobes
What is the clinical use of tigecycline?
This drug was developed to overcome tetracycline resistance in complicated skin, soft tissue, and intra-abdominal infections
How is tigecycline administered? How is is excreted? It works rapidly in ____ but not effective during ____
IV
Bile/fecal
Tissues
Bacteremia
What drugs are considered the safest antimicrobials?
Macrolides (ketolides)
Name three macrolides
Erythromycin
Clarithromycin
Azithromycin
Macrolides bind _____ to ____ subunits to inhibit the _____ step of protein synthesis
Irreversibly
50s
Translocation
Are macrolides bacteriostatic or bacteriocidal? Are they broad spectrum or narrow spectrum?
Bacteriostatic
Broad spectrum
True or false… macrolides can be used to treat MRSA
False
What are some clinical uses for macrolides?
2nd line agents for skin and soft tissue infections (not MRSA), frequently used for upper respiratory infections, and community acquired pneumonia
Which macrolides has the longest half-life and volume of distribution?
Azithromycin
Azithromycin is preferred therapy for urethritis caused by _____
Chlamydia
What is the difference between endotoxins and exotoxins?
Endotoxins are toxic pathogen components (like LPS)
Exotoxins are toxins secreted by pathogens
What are four challenges that pathogens present to the immune system?
Form diversity
Life cycle diversity
Diverse routes of infection
Rapid, target response over a broad domain
True or false… pathogens often infect multiple body compartments
True
True or false… pathogen physiology changes with life cycle
True
True or false… single immune response types may clear up a pathogen
False
What are primary lymphoid organs?
Where immune cells originate and develop
Bone marrow
Thymus
What are secondary lymphoid organs?
Where adaptive immune responses are intiatied and where naive and mature B and T cells reside
Lymph nodes
Spleen
Lymphatic system
Organ-specific lymph-node-like tissues (payers patches, tonsils, etc.)
The common lymphoid precursor will give rise to…
B cells
T cells
NK cells
Common myeloid precursors will give rise to…
Monocytes (that give rise to macrophages and dendritic cells)
Granulocytes (which include neutrophils, eosinophils, basophils)
Mast cells
RBCs
Megakaryocytes (give rise to plasmids)
True or false.. lymph flow is bidirectional
False, it is unidirectional. It involves valves, smooth muscle, pressure gradient, and drains into the venous system
What are the three stages to a generalized response to an infection?
Immediate innate
Induced innate
Adaptive immune response
What three components are part of the immediate innate system?
Barriers
Antimicrobial peptides
Complement
What are the components of the induced innate immune response?
Inflammatory cells (neutrophils, monocytes (macrophages and dendritic cells), natural killer cells
Tissue resident cells (that require activation) - basophils, eosinophils, mast cells
What are the three primary antigen presenting cells?
Dendritic cells
Macrophages
B lymphocytes
Naive lymphocytes are activated in the ___
Lymph nodes
If activated, the naive lymphocytes will undergo expansion
Activated lymphocytes travel from the lymph to the infection site
What are CD8 and CD4 T cells? What receptor do each of them bind to?
CD8 = cytotoxic T cells. These target cells specifically and kills them (CD8 binds to MHC 1)
CD4 = T helper cells. Activate macrophages and B cells (binds to MHC 2)
An activated B cell forms numerous ____
Plasma cells
True or false… antibodies may target more than one antigen
False
What is the difference between A subunits and B subunits of toxins?
A subunit - responsible for enzymatic activity of the toxin
B subunit - mediates binding to a specific receptor and transfer of the A subunit across the membrane
