Theme 4 - professional pathogens Flashcards
what is the definition of infection?
when an organism enters the body, increases in number and damages the host in the process
What is the definition of colonisation?
organism is present but doesn’t cause infection (may precede infection and amount an immune response)
what is the definition of a pathogen?
an organism that evades immune defences of a normal human host to cause infection
what step may precede infection?
colonisation
what is the definition of a commensal?
lives on us but doesn’t cause infection
what is symbiosis
mutual benefit
what is a parasite
unequal benefit - advantage to the micro-organism over the host
how often do professional pathogens cause disease?
almost always
how often do opportunistic pathogens cause disease?
only in specific situations eg in immunocompromised patients
what type of pathogen can commensals potentially be?
opportunistic
why do some organisms cause infections and others dont?
because they vary in virulence
what is virulence?
the fundamental property of an organism
what sits at either end of the spectrum of pathogenicity?
commensal and pathogen
name two commensal organisms
lactobacillus case and propionibacterium acnes
name two organisms in between commensal and pathogen on the spectrum of pathogenicity
Candida albicans and staphylococcus epidermis
name three organisms at the pathogenic end of the spectrum of pathogenicity
staph aureus, malaria, HIV, neisseria meningitidis and strep pneumoniae
in what situation can organisms with low virulence be pathogens?
in immunocompromised patients
what is pathogenicity?
the probability that an organism is causing disease when its isolated from a patient
what determines pathogenicity?
the virulence of the organism and the immune state of the patient
what three factors determine whether a pathogen from a patient is pathogenic or commensal?
the immune status of the patient, the site the sample was taken from (is it sterile) and the virulence of the organism
what are four key features of staph aureus
commensal of the anterior nares, form golden colonies on agar, gram positive cocci they associate in clusters, very virulent
what three features make staph aureus very virulent?
its surface proteins (adhesins), secreted proteins (toxins) and polysaccharide coat (capsule)
what can allow staph aureus to be distinguished from other less virulent staphs?
the specific adhesins and excretions that allow the disease to manifest
what three features make staph aureus unique?
adhesins that bind to host proteins, cloaking and protein A
what do adhesins on staph aureus do?
bind host proteins
what is cloaking?
when an organism (eg staph aureus) coats itself in host proteins to evade the immune system
what does protein A on staph aureus cell surface do?
binds the fc portion of IgG (wrong way round) and therefore coats itself in the Ig to allow immune escape
what test can be used diagnostically for staph aureus?
coagulase test
how and why does the coagulase test for staph aureus work?
staph aureus has coagulase enzyme on its cell surface so will coagulate sheep serum
what is the purpose of the coagulase enzyme on staph aureus cell surface?
is a virulence factor - stimulates blood clotting around an infection to stop WBC getting there are clearing it
what type of staph are coagulase negative?
staph epidermis
what are three key staphylococcal toxins?
cytotoxins, exfoliative toxins and enterotoxins
how do staph cytotoxins cause damage?
form pores in the cell membrane and lyse host cells (PVL blows up macrophages)
how do staph exfoliative toxins work?
degrade connective tissue in the skin - target epidermal structures so skin falls off (proteases)
how do staph enterotoxins work?
aka superantigens. stimulate T cells and confuse the immune system
where are many staph toxins encoded?
on mobile genetic elements - can move between strains and are only present on a proportion of strains
what feature of staph aureus allows it to evade the immune system (opsonisation)
the thin polysaccharide capsule - covers surface antigens tthat antibodies normally bind to (eg peptidoglycan)
name three staph aureus skin infections
furunculosis, staph abscess and impetigo
what is the most common type of staph aureus infection?
line sepsis
what type of toxins produced by staph aureus cause impetigo?
exfoliative toxins
what is the most common cause of staph aureus infection?
bacteraemia (bacteria in the blood) - causes endocarditis, osteomyelitis and septic arthritis
name three common sites of staph aureus infection
skin/soft tissue, surgical site, vascular line, blood
is staph aureus usually commensal?
yes (in anterior nares)
what happens in staph aureus food poisoning?
rapid brief illness, lots of vomiting and a little diarrhoea (caused by enterotoxins)
name four ways that staph aureus demonstrates its virulence
adherence to nasal mucosa (adhesins), invasion of tissues (cytotoxins and enzymes), evades immune clearance (protein A and capsule), replicates and disseminates
how does staph aureus gram stain?
gram positive- purple
what additional mechanism of virulence do gram negative bacteria have?
lipopolysaccharide
how sensitive is the immune system to lipopolysaccharide?
very - allows early detection of infection and can recognise it rapidly at very low concentrations
what type of receptors does LPS interact with?
toll like receptors - especially TLR4 on monocytes and in the endothelium
what is the result of interaction between LPS and TLRs?
activation of inflammatory pathways, coagulation and clotting pathways, changes in endothelial integrity
why do people get so sick with gram negative infections?
due to the release of LPS (endotoxin) in the blood - causes systemic activation of immune responses
is LPS endogenous or exogenous in bacteria?
endogenous
do gram positive bacteria have LPS?
no - they have lipoteichoic acid and peptidoglycan that stimulate different TLRs to gram negative bacteria
what organism causes meningococcal septicaemia?
neisseria meningitidis
name two key features that contribute to the pathogenicity of neisseria meningitidis in meningococcal septicaemia
the pathogen has adhesins the stick to the throat, resp epithelium and meninges, it sheds LPS off the surface and into the surroundings (blebbing)
what does blood stained sputum indicate?
pneumococcal pneumonia
what type of bacteria causes pneumococcal pneumonia?
gram positive diplococci - pneumococcus
what are the symptoms of pneumococcal pneumonia?
cough, breathlessness, consolidated lung (pus filled), haemoptysis (blood stained sputum) - can cause disseminated disease
name four factors that contribute to streptococcus pneumoniae virulence
specific adhesins for the respiratory mucosa, pneumolysin, secretion of IgA protease (and other toxins), capsule, LPS, lipotechoic acid and peptidoglycan
how does pneumolysin convey virulence in streptococcus pneumoniae
binds cholestrol on host cell membrane, forms pores and lyses ciliated cells, lyses phagocytic cells
how does IgA protease convey virulence in streptococcus pneumoniae
breaks down secreted IgA to prevent mucosal clearance
how does the bacterial capsule convey virulence in streptococcus pneumoniae
prevents complement mediated phagocytosis (need specific antibodies to target it)
how many different types of capsule are there in strep pneumoniae?
> 100 types
where can strep pneumoniae disseminate to?
blood, heart valves (endocarditis), upper respiratory tract (sinusitis, Otis media) and meninges (meningitis)
name four key features of clostridium difficle
gram postive rods, anaerobic, spore forming and cause wound/GI infections
name three types of c difficile
c. tetani, c. botulinum and c welchii
what aspect of c difficile makes it easy to spread between hospital patients?
it is spore forming so is resistant to drying, alcohol and antibiotics
where are c difficile spores found?
in soil and in the gut of humans and animals
what is one of the main symptoms of c difficile?
diarrhoea - can be mild or severe but may lead to gut perforation and death
what infection is severe pseudomembranous colitis a symptom of?
clostridium difficile
what two key things contribute to c difficile pathogenicity?
production of toxins that cause fluid secretion into the gut (diarrhoea and increased infectivity) and spore production (difficult to control and easy to relapse on treatment)
what happens in some virulent strains (027) of c difficile
loss of regulation and hyper production of toxic genes, production of additional toxins
