Specific pathogens (bacteria and fungi) Flashcards
Shigella and salmonella are
Intracellular pathogens
What is an important element of salmonella and shigella?
T3SS
Shigella
Gram negative rod
Salmonella
Gram negative rod
Neisseria meningitidis
Gram negative bacterium
Neisseria meningitidis virulence?
Lipopolysaccharide in the outer membrane> endotoxin responsible for septic shock and haemorrhage due to the destruction of red blood cell.
How does neisseria meningitidis avoid phagocytosis?
Polysaccharide capsule
How does neisseria meningitidis attach to nasopharynx?
Fibriae to mediate attachment to the epithelial cells of the nasopharynx.
How does neisseria meningitidis evade adaptive immune system?
Produce IgA protease to cleave IgA antibodies.
How does neisseria meningitidis inhibit complement?
Has a factor H binding protein - inhibit the alternative complement pathway.
Streptococcus pneumoniae
Gram positive cocci
How is strep pneumoniae haemolysis different in aerobic vs anaerobic conditions?
Alpha haemolytic under aerobic or beta haemolytic under anaerobic bacteria.
How does strep pneumoniae avoid phagocytosis?
Capsule inhibits phagocytosis by immune cells.
Streptococcus pyogenes
Gram positive coccus
Is streptococcus pyogenes part of the normal flora?
Yes
What does it haemolyse/ Lancefield group
Beta haemolytic.
Predominant species harbouring the Lancefield group A antigen
What does strep pyogenes cause?
Pharyngitis, cellulitis (strawberry rash), rheumatic fever and glomerulonephritis.
Strep pyogenes toxin?
Streptococcal pyrogenic exotoxin A (SpeA) superantigen
Responsible for the rash of scarlet fever and responsible for many of the symptoms of streptococcal toxic shock syndrome.
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How does strep pyogenes evade DNA?
Secretes DNases to digest NET’s web of DNA
How does strep pyogenes evade complement?
C5a peptidases cleaves C5a, a potent neutrophil chemotaxin.
What does streptokinase do?
Enzymatically activates plasminogen’s plasmin to digest fibrin and other proteins.
What releases streptokinase?
Strep pyogenes
Streptococcus pharyngitidis is
Strep throat causing group A streptococcus (i.e pyogenes)
Where is staph aureus found?
Flora of the upper respiratory tract and on the skin
Is staph aureus found in the microbiota?
Not part of the normal microbiota: when it is prevalent here, it is a colonisation.
What is a commensal?
Colonises in around 30% of the human population
What does staph aureus cause?
Abscesses, surgical wound and burn infections, food poisoning
How can staph aureus evade phagocytosis?
Produces coagulase to clot plasma and coat bacterial cell
What toxins does staph aureus release? What do they cause?
TSST1 - toxic shock syndrome
Enterotoxin -gastroenteritis
(Superantigens)
Exfoliation toxin - acts as a protease that cleaves desmoglein in desmosomes - scalded skin syndrome
How does staph aureus evade the adaptive immune system?
IgG binding protein, binds to the Fc region of an antibody.
Clostridium difficile is .
Gram positive rod spore forming, anaerobic motile bacteria.
Prevalent in soil
Clostridium tetani
Common soil bacteria causes tetanus. Forms spores.
What toxins do C.diff produce? What effect?
Enterotoxin A and cytotoxin B, which disrupts the cytoskeletal signal transductions in the host by targeting and inactivating Rho family of GTPases.
Produce inflammation and diarrhea (bloody).
What is the tetanus toxin, what effect does it have?
Tetanospasmin (i.e tetanus toxins) responsible for symptoms of tetanus by blocking the release of inhibitor neurotransmitters glycine and gamma-aminobutyric acid at motor nerve endings - widespread activation of motor neurons and muscle spasms throughout the body.
What is the only natural reservoir of shigella?
Humans
Escherichia coli..
Gram negative anaerobic rod
Most e.coli are..
Harmless but some serotypes (EPEC, ETEC) etc can cause serious food poisoning
E.coli transmission
Fecal-oral transmission.
E.coli what colour on MacConkey agar?
Appears pink on MacConkey’s agar.
Shigella causes?
Dysentery and diarrhoea
Shigella toxin?
Shiga toxin, which is haemolytic similar to the verotoxin produce by enterohemorrhagic E. coli.
Shiga toxin can cause potentially fatal haemolytic-uremic symptoms. Secretes toxin via T3SS.
What causes typhoid fever?
Salmonella invading the bloodstream (typhoidal form) or spreads through body, invades organs, and secretes endotoxins (septic form - septic shock).
What do non-typhoidal salmonella cause?
Non-typhoidal serotypes cause a self-limiting GI disease by entering via M cells in the gastric mucosa.
What is EHEC? What does it cause?
Enterohemorrhagic E coli.
Responsible for outbreaks of bloody diarrhoea and haemolytic ureic syndrome (HUS: loss red blood cells, acute kidney failure, low platelets.)
What is ETEC? What does it cause?
Most common cause of traveller’s diarrhoea (enterotoxigenic E coli).
What is EPEC? What does it cause?
Enteropathogenic E coli.
What is EPEC? What does it cause?
Enteropathogenic E coli.
Causes diarrhoea.
EPEC infection results in
Infection results in a decrease of Cl-/HCO3- exchange and NHE3 via EPECs T3SS.
Increased permeability and water follows Cl- into the intestinal lumen.
What toxins to ETEC produce?
Heat labile enterotoxin (LT) and heat-stable enterotoxin (ST)-LT
How does heat labile enterotoxin act?
Acts (after entry and acidification in endosome) by raising cAMP levels through ADP ribosylation of the alpha subunit of the Gs protein, leading to constitutive activation of AC.
Stimulate activation of the CFTR channel - stimulating secretion of chloride ions into gut lumen - water follows.
Loss of electrolytes and water
What is enteric O antigen?
Represents the polysaccharide component of the gram negative LPS. (Enteric= natural habitat is the intestinal tract of humans and animals).
N gonorrhoeae
Gram negative coccus
Causes sexually transmitted genitourinary infection gonorrhoea, as well as septic arthritis, disseminated gonococcemia, gonococcal ophthalmia neonatorum.
How is N gonorrhoeae transmitted?
N gonorrhoeae may be transmitted through vaginal, oral or anal sex.
How does gonorrhoeae present differently in men and women?
Men are more often asymptomatic carriers of gonorrhoea.
After infection with N gonorrhoeae what happens?
After infection, the bacterium adheres to epithelial cells via type IV pili, at the mucosal site that is infected.
After adherence, the bacterium replicates into microcolonies - Stimulates release of cytokines and chemokine from host immune cells - recruitment of macrophages and neutrophils.
How does N gonorrhoeae evade the immune response?
Opa proteins to bind receptors on immune cells and prevent immune response. These proteins undergo phase variation: frameshift result in different Opa genes being translated every time.
Via antigenic variation (rearrangement of the pilli gene)
How is N meningitidis spread?
Through saliva and respiratory secretions during coughing, sneezing, kissing chewing on toys etc.
How does sialyation produce evasion?
Sialylation of the lipopolysaccharide causes resistance to serum bactericidal activity.
Not seen as foreign
How do super antigens work?
Superantigens/ enterotoxins are capable of indiscriminately activating T cells of the immune system causing system wide inflammation and other serious- potentially fatal- symptoms.
How are spores formed? Why is it beneficial
Triggered by lack of nutrients, usually occurring in gram positive bacteria. It is a non-reproductive structure, enabling bacterium to survive long periods of environmental stress.
What do salmonella and shigella turn MacConkey’s agar?
Doesn’t ferment lactose, yellow
Gram negative rod grows on MacConkey;s agar, can ferment lactose but is unable to ferment indole from tryptophan…
Klebsiella
What bacteria is more sensitive to beta lactam antibiotics?
Gram positive
Acid fast stain bacteria stain pink with
Carbolfuschin (counter stain is blue).
Most common bacteria to cause septic shock are…
Streptococcus pneumoniae, neisseria meningitidis and staphylococcus aureus.
Gram positive rod grows aerobically and can form spores
Bacillus
Does salmonella have an animal reservoir?
No animal reservoir
What state does salmonella reach in humans?
Chronic carrier state in humans.
Pseudomonas aeruginosa
Encapsulated, gram negative, rod shaped.
What does pseudomonas cause?
Causes pneumonia, septic shock, UTI, necrotising enterocolitis, and haemorrhage and necrosis (e.g people with burns.)
What is the most frequent coloniser of medical decides e.g catheters?
Pseudomonas aeruginosa
This commensal microorganism has a rigid cell wall, and is capable of causing opportunistic infections of the mouth, gut and vagina. Infections are more common in people with HIV infection.
Candidas albicans
Infection with this human pathogen, for which an effective vaccine is not available, is treated with chloroquine, artemesinin derivatives and doxycycline.
Malaria
Which human pathogen is best described by the following statement?
Promastigotes of this protozooal parasite are transmitted to humans by the bite of the sandfly. The promastigotes enter macrophages where the parasite replicates. The most common clinical manifestation is non-healing raised skin lesions.
Leishmeniasis (infantum or chagasi or donovani)
Which human pathogen is best described by the following statement?
This single celled pathogen causes a form of pneumonia in immune compromised individuals that is refractory to treatment with anti-bacterial antibiotics and used to be the leading cause of death in HIV/AIDS patients.
Pneumocystis jirovecii
This filamentous fungus produces spores that can trigger a type III immune pathology in the lung of sensitized individuals due to the build up of antigen/antibody complexes that trigger complement activation.
Aspergillus clavatus
In the small intestine, cholera toxin acts by
ADP-ribosylation of Gs which makes it constitutively active which results in phosphorylation and activation of Cl- channels
A protein filament that facilitates the attachment between bacterial cells during conjugation.
Sex Pilus
A polymer of glycerol phosphate or ribitol phosphate that is present in the cell wall of Gram positive bacteria.
Teichoic acid
A non-reproductive structure formed by some Gram positive bacteria, that enables the bacterium to withstand long periods of environmental stress.
Endospore
What is a cause of blood-stained sputum?
Streptoccocus pneumoniae, hameophilus influenzae, staphylococcus pneumoniae
Which one of the following bacteria grows on MacConkeys agar plates and ferments lactose?
E. Coli or Klebsiella
“A Gram negative coccus that resides in the nasopharyngeal tract of humans. After colonising the nasopharynx, bacteria can cross the nasopharyngeal epithelium to enter the blood stream where the bacteria proliferate and, if unchecked, can lead to a fatal septicaemia”
Neisseria meningitidis
Staphylococcus epidermidis is best described as a:
Opportunist pathogen, is part of the flora on the skin but can become pathogenic infecting artificial heart valves and prosthetic limbs, catalase positive, coagulase negative, Gram-positive
Which bacteria grows as a Gram positive obligate anaerobe that forms spores?
Clostridium
Which cells does LPS primarily act on?
Macrophages
How is LPS released by bacteria?
Not released, integral part of cell wall
How is tetanus treated?
Treated with tetanus antitoxin + benzodiazepines (prevent spasm)
How is pneumonia transmitted (strep pneumoniae)?
Pneumococcal infections are not considered communicable (no animal resevoir), usually part of normal flora and cause disease when predisposing factors occur
Which Gram positive bacterium secretes an exotoxin that binds irreversibly to receptors in the spinal cord and brain stem and blocks neurotransmission by cleaving membrane proteins involved in neuroexocytosis?
Clostridium tetani or botulinum
What is fungi?
Eukaryotic organisms in the kingdom of fungi, separate from other eukaryotic life. This is because of the rigid chitin cell walls. Fungi either grow unicellularly or as hyphae.
What is athlete’s foot?
Caused by a number of different fungi.
Form of fungal infection of the skin - fungi inhabit dead layers of skin and digest keratin.
Transmitted through direct and indirect contact, particularly in warm wet environment
What causes thrush/ candidiasis ?
Candida albicans
Where is candida albicans found?
Yeast that is a normal part of the mouth, gut and vaginal microbiome. Very common in untreated HIV, often appearing before any other opportunistic pathogens.
When may candida infections become problematic?
If the normal micro biome is disrupted e.g following antibiotic treatment, candida infections can be a problem.
How can candidiasis progress?
Can develop into an invasive disease unexplained fever that is unresponsive to antibiotics, multiple non-painful cutaneous lesions, yeast in urine samples, iv catheter grows yeast.
What is ringworm/ dermotrophytosis?
Fungal infection of the skin. Can be caused by many forms of fungi.
How are fungal infections implicated in AIDS?
Fungal infections are much more common and have more potential to become problematic in individuals who are immunodeficient either from treatment, infection by HIV or genetic causes.
What are yeasts?
Fungi that grow as single cells
What is pneumocystis?
Pneumonia caused by pneumocystis defined AIDS as a syndrome at first.
Can be found in the lungs of healthy people, but is a classic opportunistic pathogen that causes pneumonia only in the immunocompromised.
Non-productive cough, weight loss, night sweats, chest X ray shows widespread infiltrates
What is cryptococcus? What does it cause?
Cryptococcus: free living encapsulated yeast.
Infection of immunocompetent patients is very rare. Usually in AIDS patients. Causes self-limiting pneumonia, large fungal mass, skin infections, meningitis. Treatment to eradicate is essential in case of CNS involvement
How does cryptococcus present in vitro?
Gives white mucoid colonies on sabour and dextrose plates.
What is aspergillus?
Filamentous fungi can cause many symptoms
What does aspergillus cause?
Bronchopulmonary aspergillosis in allergic individuals
Aspergilloma in lung cavities
Invasive aspergillosis in neutropenics and severely immunocompromised patients. This has a high mortality rate.
What do antifungals include?
Fluconazole, Nystatin, Amphotericin B
How does cryptococcus evade phagocytosis?
Capsule
How is cryptococcus stained?
India ink exclusion
How can candida grow?
Yeast, pseudohyphae and hyphae
What bacterium is TB?
Mycobacterium
Does mycobacterium gram stain? How is it stained?
No, carbol fuchsin (pink) with methylene blue counterstain
How does mycobacterium present under the microscope and why?
Unicellular with branched rods cells are seen in a cording pattern, due to the presence of fatty acids in the cell wall that stick together.
What are unique features of the Mtb cell wall?
Lipoarabinomannan (LAM)
Mycolic acids (MA)
What is LAM in Mtb cell wall?
Lipoarabinomannan (LAM): consists of 2 sugars, lipid portion which associates with cell membrane.
What is MA in Mtb cell wall?
Mycolic acids (MA): negative charge to outer membrane, associates with glycolipids, acid found in the middle, long acyl chain at one end associates with lipid (fatty acid)
What happens to 5% that cannot contain primary Tb infection?
Primary disease
What is a primary complex (TB)?
Ghon focus in combination with hilar or paratracheal lymphadenopathy
What is post primary/secondary disease (TB)?
Occurs in 5% of primary infection patients, arises from reactivation of dormant TB in organs - often decades after initial infection when host immune defence weakened
What cytokines are important in a TB infection?
IL-12 (activating Th1) IFN gamma (generated intracellular pathogen response) TNF alpha (recruits CD4+ for granuloma)
What cytokine drives macrophage fusion (TB granuloma)?
IFN gamma
What is the vaccine for TB?
BCG
What is the test for TB?
Mantoux (tuberculin) test as example: Inject tuberculin or PPD into skin
A person who has been exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins. The response is a classical example of delayed-type hypersensitivity reaction (DTH), a type IV of hypersensitivities
What type of vaccine is BCG?
Live attenuated mycobacterium bovis
What is the most likely cause for the formation of the granuloma?
Delayed type hypersensitivity immune response to MTb
What is the nature of the giant cells?
Macrophage fusion
A positive Mantoux (tuberculin) test alone is not proof of recent MTb infection
True
Up to a third of the world’s population has had a sub-clinical MTb infection
True
There are sparse or no detectable acid-fast bacilli in the granuloma
True
The lesions are rich in acid-fast bacilli
False
It can be very difficult to isolate MTb in sputum from such an infected individual
True
Do granulomas give rise to lung cancer?
No
Epithelioid cells are due to metaplasia of epithelium
False
Is BCG is effective as a vaccine against adult pulmonary tuberculosis
No
Is BCG vaccination dangerous in immunodeficient patients?
Yes
Is BCG effective against systemic spread of MTb in infants
Yes
Non-virulent mycobacteria are common in the environment
True
Maximal inflammation at a Mantoux test site?
72 hours
What bacteria has round colonies and distinctive colour?
S.Aureus
