Bacterial growth and colonisation Flashcards
What is the method of choice for bacterial growth/colonisation?
Why?
Most bacterial pathogen infections involve formation of biofilms. 80%
Biofilms can form on biotic or abiotic surfaces…. and involve adhesion before envelopment in a secreted matrix.
Biofilms can form in a niche that is optimal for growth and colonisation, where the biolfilm provides protection from the immune system, environment, disinfectants, phagocytosis, antibiotics etc.
Biofilms can be up to a thousand-fold more resistant to antibiotics.
How can biofilms lead to virulence factor production?
Biofilms contain bacteria with very high bacterial density leads to activation of Quorum sensing for the production of Virulence factors.
What matrices are there for biofilms?
Different pathogens use different matrixes.
But the matrix is produced themselves…
DNA, protein, polyaccharides.
What are some examples of bacterial biofilms?
Biofilm formation in urinary catheters cause UTIs in hospital.
Staphylococcus Aureus can infect the heart valve + form biofilm in ENDOCARDITIS.
Staph. Aureus can also infect lungs in Cystic Fibrosis.
Biofouling = biofilm formation in drain pipes…
What are the main limiting nutrients of bacteria?
Most nutrients are freely available for pathogenic bacteria… O2, glucose, ions.
EXCEPT, Iron is limited!
In the aerobic conditions of our body, iron is oxidised to ferric form (FE3+), which is highly unsoluble.
And most iron is complexed to proteins - Haemoglobin, Ferritin, Lactoferrin, Transferrin (in serum).
How do bacterial pathogens acquire iron?
The uptake of free iron or iron complexes can involve:
Direct contact using cell surface proteins. E.G TBP, HBP (Transferrin/Haemoglobin binding protein)…
Secreting small compounds (Siderophores) = v. High affinity for iron, which capture free iron or insoluble ferric salts.
How do siderophores acquire iron for bacterial pathogens?
Bacteria secrete siderophores when [iron] is very low.
Such as Enterobactin
They have a low molecular weight with v. high affinity to iron.
So compete for free or complexed iron.
Siderophores are secreted - where it competes and binds iron…
The iron-siderophore complex is transported across the PM into bacteria, where reducing conditions convert ferric iron to Fe2+.
What are the ways that pathogens evade host defence?
Needs to evade physical barriers, and the adaptive and innate immune systems.
= Needs to cross physical barriers like skin, respiratory tract cilia, stomach..
= Needs to avoid complement system and phagocytosis, and avoid antibodies.
How do bacterial pathogens avoid the complement system?
With capsules = thick polysaccharide layer around cells, which inhibit complement factor binding and activation.
LPS O-antigen = Gram -ve bacteria with LPS on outer membrane = Elongated O chains on LPS can prevent complement activation by making difficult to recognise cell as pathogenic.
How do bacteria avoid phagocytosis?
Prevent complement activation = Capsules and LPS O-antigen.
Biofilms, capsules, LPS can prevent the effective contact with phagocyte.
Streptococcus pyogenes secretes peptidases which cleave complement factor C5a = stops the labelling of pathogen with C5a, which would recruit phagocytes…
= Strep pyogenes = throat infection.
C5a is a chemotactic for neutrophils!!!
OR destroy phagocytes = leukocidins, toxins for WBC’s membrane disrupting toxins.
How can bacteria evade the immune system intracellularly?
Protection from antibodies, phagocytes, some antibiotics..
Phagocytosed bacteria can still survive….
Survive phagolysosome, prevent phagolysosome formation = sit in unfused phagosome = salmonella spp, destroy/escape phagosome to live in cytosol = Lysteria monocytogenes…
Or invade non-phagocytic cells = Using modified T3SS which prompt actin polymerisation to envelope the pathogen to enable cell entry.
= Salmonella, Pseudonomas
How can bacteria evade host-antibody responses?
Can bind host antigens/proteins so that they are less likely to be detected as foreing.
M protein is expressed by Streptococcus pyogenes…= confers phagocytosis resistance..
Strep pyogenes = protein G.
Staphylococcus aureus = protein A
= bind antibody backwards to prevent opsonisation.
What is so special about streptococcus pyogenes?
Causes throat infection.
Expresses M protein on surface to evade antibody response as less likely to be detected as foreing.
Expresses peptidases which cleave C5a, which acts as chemotactic for neutrophils, so prevent phagocytosis/recruitment of phagocytes.
Produce protein G on surface = which binds antibody backwards = prevents opsonisation.
What are the different types of toxins?
Toxins cause immediate host damage and induce inflammation.
Exotoxins are actively secreted during growth.
Endotoxins are structural parts of a microbe released when pathogen is lysed. like LPS
Toxoids are inactive/v. low activity toxins used in vaccinations. e.g for tetanus.
WHat are exotoxins?
Exotoxins are actively secreted during growth.
They are usually proteins, like enterotoxin , which are heat-labile.
Clostridium botulinum secretes botulinum toxin, with very low LD50 = causing cleavage of SNAP to prevent vACh fusion…
Host-site specific = affecting specific cells, such as neurotoxins, enterotoxins.
Membrane-disrupting toxins = leukocidins (degrade WBC’s), haemolysins (RBC’s)
Superantigen type = stimulate T cells to release cytokines, but do so excessively = causing T cell storm and a mass release of nutrients for the pathogen.
