Virulence Factor Practice Questions Flashcards
Which part of an LPS molecule is most likely to lead to a protective response from the adaptive arm of the immune system?
a. Lipid A
b. Fatty acids
c. Protein
d. O repeat unit
e. Glucose
O repeat unit
What are the parts of LPS? What is the adaptive arm of the immune system? What would a protective response from this system be based on? Which part of LPS is most likely to drive that?»_space;>The immunogenic portion of the molecule is the O antigen—this is the part against which a protective antibody could be directed.
The core and lipid A could also be immunogenic (weakly in the case of lipid A) but are not particularly accessible–so antibodies would not be protective.
What is the major role of peptidoglycan?
a. Cause septic shock
b. Cause toxic shock
c. Maintain cell shape
d. Prevent phagocytosis
e. Kill host ciliated cells
Maintain cell shape
While PG fragments can do # 1, # 3, and # 5, the reason that bacteria produce PG is as a basic cellular structure. Membranes have no real structure to them, so the only part of the cell envelope that can possibly generate shape is the PG layer. How this happens is complex (and quite interesting, and not entirely understood).
Which of these is most likely to comprise the majority of a bacterial capsule? Methionine-serine-glutamate Glucose-galactose-arabinose Thymine-adenine-uracil Bactoprenol-ubiquinol Lanthanide-actinide-halogen
Glucose-galactose-arabinose
What are capsule made out of? Which of these things fit that category? The vast majority of bacterial capsules are polysaccharides, and are therefore composed of sugars.
A 57-year-old woman in the ICU develops fever and hypotension. Blood cultures grow a facultatively-anaerobic, Gram-negative bacillus which produces dark pink colonies on MacConkey agar. Serotyping reveals the presence of the K1 antigen on the bacterial cell surface, which is composed of polysialic acid. What step in the infectious cycle is most directly facilitated by this antigen, allowing the causative agent to produce this disease?
a. Transmission
b. Colonization
c. Replication
d. Host cell invasion
e. Dissemination
Dissemination: replication in the bloodstream
If you can’t remember what a K antigen is, then ask yourself what sialic acid is and then which cellular structures (on the surface, this is stated) are likely to contain it. Once you figure out it is capsule (Kapsel), then you can go on to the 2nd part of the question. Some bacterial capsules, such as the one described here, are very effective at preventing phagocytosis and also preventing complement component binding. This resistance to serum and cellular killing mechanisms means that organisms producing such capsules are able to survive (and often replicate) in the bloodstream, which is one of the most efficient ways for bacteria to spread (or ‘disseminate’) throughout the body. The argument could be made that replication in the bloodstream means it is being colonized, so the capsule contributes to this. This is definitely a good point for discussion, but consider that survival is a prerequisite to replication, and not all pathogens will replicate in the bloodstream itself; so, dissemination is the better answer (both generally and specifically).
a. Transmission: method of spreading disease after leaving body
b. Colonization: increase in number
c. Replication
d. Host cell invasion
e. Dissemination: replication in the bloodstream
What describes the way in which the polysialic acid K1 capsule prevents recognition by the adaptive immune system? Antigenic variation Blocks PRR access Binds C3b Binds factor H Mimicry
Mimicry
What is the adaptive system? What molecule recognizes microbes in that system? How might microbes prevent these molecules from recognizing them as foreign? Which of these approaches would a sialic acid capsule be exploiting?
K1 capsule is made of sialic acid, which is present on host cell surfaces. Thus, the bacterium ‘looks like’ host to the immune system, i.e. mimics the host. Antibodies recognizing sialic acid should not be produced, and seeing that this would be the predominant antigen visible to the immune system, an protective adaptive response would not be easily produced. It does bind factor H, which interferes with the alternate complement response, but this is an innate response, not adaptive.
What lets bacteria know it is time to start growing together?
a. Temperature
b. Cell density
c. Host cell receptor binding
d. Nutrient limitation
e. Attack by innate immune system
Cell density
What system helps multiple bacteria do things in a coordinated fashion? What is a basic trigger of this system?
While most of these answers are probably correct to some extent (depending on the organism), one commonality among all bacteria is the importance of quorum sensing to the process. This process allows bacteria to know how many of them are around, and thus only do certain things when there are enough. It’s a bit tough to build a city (or overrun a giant multicellular organism with strong defenses) with only a few bacteria!
Why do sessile bacteria display reversible antibiotic resistance, while their planktonic counterparts are susceptible? (choose 2)
a. Gene acquisition from many surrounding organisms
b. Genetic regulation
c. Increased rate of point mutations
d. Decreased metabolic rate
e. Drug inactivation by biofilm
Genetic regulation & Decreased metabolic rate
To what do sessile and planktonic refer in this situation? What would sessile bacteria have that planktonic ones don’t? What does “reversible” antibiotic resistance mean? How might changes within sessile organisms allow them to resist the effects of antibiotics?
Sessile bacteria are those growing in a biofilm. While in the biofilm, stress caused by difficult living conditions (including low nutrients, high toxic byproducts) lead to a genetic stress response, which makes the bacteria more resistant to reactive oxygen species and less likely to autolyse. These conditions also cause growth to slow, which means that antibiotics relying on active bacterial replication (e.g. those that target DNA synthesis, cell wall synthesis, protein synthesis among others – which is most of them) will be less effective. There is some indication that other mechanisms may also be at play, but these two are the most generally accepted.
Who is more likely to have meningococcal meningitis?
a. A 19-y-o college student who lives in the dorm and has a sore throat
b. A 19-y-o college student who lives alone and has a runny nose
c. A 19-y-o college student with no prior symptoms
A 19-y-o college student who lives in the dorm and has a sore throat
What is different between these people?
People living in crowded living quarters are more likely to get meningococcal meningitis, and initial colonization and invasion by the pathogen can lead to cold-like symptoms.
Who is more likely to get meningococcal meningitis?
a. A 6-y-o child
b. A 65-y-o man
c. A 1-y-o child
A 1-y-o child
Younger children and adolescents are more likely to get meningococcal meningitis than mid-aged children and adults. However, at the moment Streptococcus pneumoniae is still the most common cause of bacterial meningitis in all age groups, particularly among unvaccinated (or not recently vaccinated) but otherwise healthy elderly people. This is changing though, with the children vaccinated with PCV7 and now PCV13 vaccines getting older–risk used to be higher in children, is now higher in adults, and overall rates have declined in all groups (effects of PCV7 in US on incidence of invasive pneumococcal disease in a. children < 5 and b. adults >65 are shown below; Klugman 2011). Will we see continued declines with PCV13, which covers the 19A serotype and was introduced in 2010? Early evidence says yes (30000 fewer cases of invasive pneumococcal disease and 3000 fewer deaths in US over 3 years following introduction of PCV13; Moore et al. 2015).
What are two important virulence factors associated with meningococcus?
a. LPS and capsule
b. Capsule and superantigen
c. LOS and superantigen
d. Lipid A and superantigen
e. Lipid A and capsule
E. Lipid A and capsule
What is meningococcus? What parts does it have that are relevant to the way in which it causes disease?
Neisseria does not make a superantigen, and a small (but seemingly important) point is that it produces LOS, not LPS. Capsule allows the organism to survive and thrive in the bloodstream, which allows it to cause sepsis and also gives it the chance to reach the CNS, where it causes meningitis. But, don’t get caught by the ‘buzzword’ LOS–when paired with superantigen, this makes that choice incorrect. Remember that LOS contains lipid A, which is the component of the molecule causing the innate immune response.
A 37-year-old woman in the surgical recovery ward develops a high fever, hypotension, and confusion. The symptoms are due to overwhelming cytokine production triggered by a bacterial protein that activates T-cell receptors in the absence of MHC and cofactor stimulation. What are the characteristics of the most likely causative agent?
a. Gram -, oxidase + rod
b. Gram -, encapsulated diplococcus
c. Gram +, sporulating rod
d. Gram +, facultatively aerobic coccus
e. Gram +, encapsulated diplococcus
f. Gram -, flexible spirochete
D. Gram +, facultatively aerobic coccus
Superantigens: Staph enterotoxins, TSSTs, Strep pyrogenic toxins
What type of protein is being described? What organisms produce these? What are the characteristics of these bacteria?»_space;»The question is describing a superantigen. These are produced by bacteria such as Streptococcus pyogenes and Staphylococcus aureus. Streptococcus pyogenes is a Gram +, aerotolerant anaerobe that is usually found in long chains. Staphylococcus aureus are Gram + cocci in clusters, which can produce energy in the presence or absence of oxygen (thereby being classfied as facultative aerobes or facultative anaerobes, which are essentially the same thing).
In May 2011, an outbreak of foodborne illness, complicated in many cases by hemolytic uremic syndrome, was seen in Germany. In thousands of patients, the causative agent was identified as a Shiga-toxin producing, Gram-negative, oxidase-negative rod that fermented lactose. A novel finding was that the isolates had the serotype O104:H4:K9, indicating that there was a common source for the infection and that it was a pathogen that had not previously been seen. What bacterial structures/components were useful in determining the serotype of this organism?
LPS, flagella, capsule OMPs, haptens, kinetoplasts Histones, peptidoglycan, teichoic acid Flagella, lipid A, pili Pili, transpeptidases,
A. LPS, flagella, capsule
Remember O, H, and K antigens? This is how Escherichia coli strains are serotyped. Refer back to the Bacterial Cell Structure material if necessary. Also, remember that serotyping schemes may be organized and named differently for different organisms; they may be lettered or numbered, and not use the O/H/K designations.
A 42-year-old man presents with burning epigastric pain. Investigations reveal that he is suffering from a peptic ulcer caused by Helicobacter pylori infection. This organism has an atypical form of the molecule forming the outer leaflet of the outer membrane. To which aspect of pathogenesis of this organism does this deviation from normal contribute?
Protection from phagocytosis Antigenic variation Reduction of host innate response Adhesion to host cell receptors Production of urea-degrading enzymes
Reduction of host innate response
structural toxins: Lipid A, peptidoglycan, lipoteichoic acids, lipoarabinomannan
pathology caused by immune response….no activity on host components!!!!!
What forms the outer leaflet of the outer membrane? What is the usual role of this molecule? How does that occur? The version here is “atypical”, so what process that normally happens would be altered if this molecule has a different form? This question refers to lipid A, which is a PAMP (pathogen-associated molecular pattern). PAMPs are normally recognized by pathogen recognition receptors (PRRs), which are part of the innate immune system and activate this response when they recognize the presence of these conserved structures. If the structure of a PAMP is unusual (i.e. the pattern is changed), then the PRRs which have evolved to recognize the typical structure of that PAMP will not be able to recognize it as well. Many commensal organisms and pathogens able to cause long-term disease have evolved to be less provocative to the innate immune system.
A 16-year-old boy is brought to the emergency department after a car accident. He has multiple contusions, broken bones, and burns to the upper torso. What are the characteristics of a biofilm-forming environmental opportunist that is of particular concern in burn patients?
a. Gram-negative, oxidase-positive, motile bacillus
b. Gram-positive, catalase-positive, coagulase-negative bacillus
c. Budding yeast
d. Gram-positive, catalase-positive, coagulase-positive coccus
e. Gram-negative, oxidase-positive diplococcus
Gram-negative, oxidase-positive, motile bacillus
A patient in the ICU develops diarrhea after several days of treatment with broad-spectrum antibiotics for a severe infection. The causative agent is found to be a Gram-positive, strictly anaerobic rod that produces an enterotoxin (called toxin A) that affects a target host cell’s ability to polymerize actin. The C-terminus of this protein binds specific glycosidic structures on the host surface, and after endocytosis the N-terminal glucosyltransferase domain is autoproteolytically cleaved and enters the cytoplasm. What term best classifies the C-terminal part of this protein? ‘C’ domain Type III secretion domain Type III secretion domain ‘A’ domain Correct Answer ‘B’ domain
Correct Answer: ‘B’ domain
What is the C terminus doing (given in the question)? What type of toxin is toxin A, given the description in the question?»_space;»For this type of toxin, what is the name of the part that has the role filled by the C terminus? This is describing an AB toxin (enzymatic component, binding component, and entry by receptor-mediated endocytosis). The B part is the part involved in cell receptor recognition/attachment/binding and triggering endocytosis.
