Microbiology Flashcards
What molecules opsonise fungi?
Pentraxin-3 and mannose binding lectin (MBL).
Which immune cells are involved in anti-fungal responses?
Phagocytes (e.g. neutrophils): the first line of defence.
NK cells: provide early interferon gamma.
Dendritic cells: influence T-cell differentiation.
Th1 and Th17 cells play a role.
Give some virulent features of different fungal spores.
Candida - dimorphism allows tissue invasion
Cryptococcus - capsule evades phagocytosis
Aspergillus - inhaled as candida, invade as hyphae (this fungal morphogenesis can drive a modulation of dendritic cell response - confusing the immune response).
Describe how dectin 1 deficiency leads to mucocutaneous fungal infections (N.B mucocutaneous refers to the region of transition from mucosa to skin).
Dectin 1 is a fungal pattern recognition receptor (PRR) - whose deficiency leads to impaired IL-6 production and binding in response to fungal infections.
Describe how CARD-9 deficiency leads to chronic mucocutaneous candidiasis.
CARD-9 is required for TNF-A production in response to B-glucan (a PAMP on the fungal cell wall) stimulation, and for Th17 differentiation.
How do TLR4 and plasminogen polymorphisms confer increased susceptibility to fungal disease?
TLR4 polymorphisms leads to an increased risk of invasive Aspergillosis (IA) in transplantation.
Plasminogen directly binds to Aspergillus fumigatus conidia - hence mutations increase susceptibility to infection.
Describe the main cellular defence against fungi.
Neutrophils: produce NETs - chromatin “nets” which capture pathogens and act outside the nucleus as “danger signals” - recruiting effector cells to the area.
Define the term fungal morphogenesis.
Fungi can transition between yeast, candida and hyphae (multicellular) forms which can drive a modulation of dendritic cell response which confuses the immune system leading to a less effective response (since dendritic cells modulate adaptive immune responses).
Describe how the immune system can be augmented to treat fungal infection.
Adoptive immunotherapy: generation of antifungal T-cells (which produce interferon gamma) in a sample which are then given to the patient.
Gene therapy: restore function in a primary immunodeficiency (e.g. gp91).
Describe how host responses to the many fungal spores inhaled daily changes the outcome.
Host response may be normal, ineffective or exaggerated leading to allergic or invasive fungal disease. Aspergillus is a primary driver.
Which hypersensitivity reactions are involved in fungal allergies?
Type 1: IgE-driven, involving histamine and leukotrienes, taking minutes.
Type 3: IgG and IgM-driven, involves complement, 1-24 hours.
Type 4: T-cell driven, involving lymphokines, 2-3 days.
(Types 1,3 and 4).
Describe the diagnosis of allergic bronchopulmonary aspergillosis (ABPA)
Predisposing conditions: asthma, cystic fibrosis.
Obligatory criteria - high baseline serum IgE, positive T1 hypersensitivity skin test (immediate) OR aspergillus-specific IgE.
Supportive criteria (2+): eosinophilia, IgG AB to Aspergillus, consistent radiological abnormalities (dilated bronchi, thick walls, lobar collapse due to mucus impaction, ring or linear opacities, fibrotic scarring).
Describe the treatment of allergic bronchopulmonary aspergillosis (ABPA).
Corticosteroids.
Itraconazole (steroid-sparing agent) - benefit past 16 weeks unclear. Indicated if not responding to steroids or is steroid-dependent.
Omalizumab - recombinant IgE monoclonal antibodies may be useful.
What is hypersensitivity pneumonitis (extrinsic allergic alveolitis)?
Allergic response following fungal sensitisation requiring long-term exposure (hence is often occupational). Cell-mediated delayed sensitivity reaction.
Describe aspergillus rhinosinusitis.
May be allergic or invasive. Association with atopy & nasal polyposis. Obliterated sinuses with hypoattenuated mucosa.
Treatment: oral corticosteroids, surgical removal of obstructing nasal tissue. Systemic anti-fungal treatment not shown to be effective.
Give different exotoxins produced by bacteria.
Neurotoxins - act on nerves and motor endplate i.e. tetanus or botulinum toxins.
Enterotoxins - act on GI tract to cause infectious diarrhoea (cholera, E Coli) or food poisoning (Staph aureus).
Pyrogenic exotoxins - stimulate release of cytokines (Staph aureus, Streptococcus pyogenes).
Tissue invasive exotoxin - allow bacteria to destroy and tunnel through tissue - enzymes destroy DNA, collagen, fibrin, NAD, RBCs, WBCs.
What are bacterial endotoxins?
Only produced by gram negative bacteria - not proteins but a lipid moiety of LPS. Shed in steady amounts by living bacteria.
Treating gram negative bacteria with antibiotics can sometimes worsen the condition (when bacteria lyse they release large quantities of LPS/endotoxin leading to septic shock).
Define microbe outbreak.
A greater-than-normal (or than expected) number of individuals infected/ diagnoses within a period or time, or in a particular place (or both).
Explain why surveillance and testing are necessary to identify outbreaks, and define possible, probably and confirmed epidemic cases. (Rewritten since Covid-19 outbreak).
Surveillance provides an opportunity to identify outbreaks.
Good and timely reporting systems are instrumental to identify outbreaks.
Possible epidemic case: Any person that has developed the symptoms AND has met a laboratory criteria (e.g. isolation of agent).
Probable epidemic case: Any person that has met the above criteria AND has been in epidemic country, consumed possibly contaminated food, been in close contact with a confirmed epidemic case.
Confirmed epidemic case: Any person meeting criteria for a possible case AND has had strain isolated.
Give common communicable bacterial respiratory tract infections in Europe and their virulence factors.
Legionnaire’s disease (legionella pneumophilia (gram negative)) - lives in amoeba in ponds, lakes, air conditioning. Route of infection is inhalation of infected aerosols. Grows in alveolar macrophages.
Virulence factors: type IV secretion systems: legionella replicates in legionella containing vacuoles (LCVs) inside cells. Type IV secretion systems transport proteins from the cytosol to inside the vacuole.
Tuberculosis (mycobacterium tuberculosis (gram positive)). Virulence factor - has an extra lipid layer (making treatment more difficult) and can enter a dormant state for reactivation.
Give common communicable bacterial sexually transmitted infections in Europe and their virulence factors.
Chlamydia - chlamydia trachomatis (Gram negative obligate intracellular parasite).
Most common STI in Europe and causes >3% of the world’s blindness.
Gonorrhoea - neisseria gonorrhoeae (gram negative).
Causes urogenital tract infections by interacting with non-ciliated epithelial cells. Virulence factors - pili, antigenic variation mechanisms (which allow it to escape detection and clearance by the immune system).
Give common communicable bacterial food and waterborne infections in Europe and their virulence factors.
Campylobacter - most infectious GI disease in EU - small children 0-4 most at risk. Infection via uncooked poultry - sporadic cases (not outbreaks).
Virulence factors: adhesion, invasion factors, flagella motility, Type IV secretion systems, toxins.
Salmonellosis (gram negative) - undercooked poultry, children 0-4 - outbreaks.
Virulence factors: type III secretion systems encoded on pathogenicity islands.
Cholera (vibrio cholera (gram negative)) - acute severe diarrhoeal disease - T4 fimbria, cholera toxin (increased cAMP - opening of Cl- channels, expulsion of water from cells) - carried on phages. Without prompt rehydration, death can ensue quickly.
Listeriosis (listeria monocytogenes (Gram positive)) - risk groups of immunocompromised and pregnant people. Virulence - actin-based cell motility. Can enter tight barriers.
Give the bacteria responsible for plague and Q fever.
Plague = yersina pestis (gram negative).
Q fever = coxiella burnetti (gram negative)
Give the bacteria responsible for the 6 bacterial infections which have effective vaccines.
Diphtheria = clostridium difficile (positive)
Invasive HA disease = haemophilus influenzae (negative)
Invasive meningococcal disease - neisseria meningitides (negative)
Invasive pneumococcal disease - streptococcus pneumoniae (positive)
Pertussis = bordetella pertussis (negative)
Tetanus = clostridium tetani (positive)
Define antimicrobial
An agent that interferes with growth and reproduction of a ‘microbe’
Define antibacterial
Describes agents which reduce or eliminate harmful bacteria
Define antibiotic
A type of antimicrobial, used as medicine for humans and animals. Originally referred to naturally occuring compounds.
Define healthcare-associated infection (HAI).
An infection that occurs after exposure to healthcare. The infection typically starts >48 hours after admission
1 in 18 patients contract a HAI.
What are the causes of a HAI?
Concentration
Dissemination
Interventions (chemotherapy, lines (IV, central, arterial), catheterisation, intubation, prosthetic material, inappropriate prescribing.
The major pathogens causing HAIs were abbreviated to “ESKAPE”, now changed to “ESCAPE” - give these pathogens.
ESCAPE E = enterococcus faecium S = Staphylococcus aureus C = Clostridium difficile A = acinetobacter baumanii P = pseudomonas aeruginosa E = enterobacteriaceae
ESKAPE - K = klebsiella pneumoniae, E = enterobacter species.
What is the problem with antibiotic resistance, in terms of clinical use?
Clinicians are forced to use older, previously discarded drugs, such as colistin, that are associated with significant toxicity and for which there is a lack of robust data to guide selection of dosage regimen or duration of therapy.
Describe the relationship between E-Coli and cephalosporins.
E-Coli is the most frequent gram-negative bacteremia.
Cephalosporins are a class of B-lactam antibiotics which inhibit peptidoglycan synthesis by inhibiting the activity of penicillin binding proteins (PBPs).
E-Coli can express extended spectrum B-lactamase (ESBL) - a mobile gene encoded on a plasmid. ESBL enzyme cleaves cephalosporin.
How can E-Coli become resistant to carbapenems?
Carbapenems are a class of B-lactam antibiotics which inhibit peptidoglycan synthesis by inhibiting the activity of penicillin binding proteins (PBPs).
Carbapenemase enzyme is encoded on a transposon.
Resistance much less common than resistance to cephalosporins.
Describe methicillin resistance in MRSA
Most important cause of antimicrobial resistance infection worldwide.
Methicillin is another B-lactam. Targets peptidoglycan synthesis by inhibiting the activity of penicillin binding proteins (PBP). Resistance arises from expression of additional penicillin binding protein . PBP2A has low affinity for methicillin and can still function in the presence of the antibiotic.
Hence, MRSA can synthesise peptidoglycan and survive in the presence of methicillin.
Describe vancomycin resistant enterococcus faecium.
3rd most common nosocomial blood stream infection.
Resistance around 60%.
Vancomycin binds to peptidoglycan precursor (a pentapeptide on NAM (N-acetyl muramic acid).
Resistance arises via multiple protein genes encoded on plasmid or transposon which result in the synthesis of a different peptidoglycan precursor.
How can Listeria cross cells?
Listeria binds to E-cadherin on the surface of cells, triggering internalisation by endocytosis/phagocytosis. Once within an acidic compartment, it produces lysin to break down the vacuole.
Listeria expresses ActA at one pole of the bacterium. ActA itself can bind actin in the host cell, however full motility requires VASP binding by the proline rich region of the protein. This recruits Arp complexes which act as nuclei for new actin filaments, increasing the rate of comet tail formation greatly. It also recruits profilin, which enhances polymerisation by replacing ADP with ATP on actin monomers. The preferred end of the new filaments are oriented towards the bacterium.
