bacterial pathogenicity

Question 1

what are virulence factors?

Answer 1

specialised gene products produced by the bacterium in order to thrive in the host

Question 2

what are the key events in bacterial pathogenesis?

Answer 2

colonisation, multiplication, damage and transmission

Question 3

what are the key characteristics of virulence genes?

Answer 3

theyre not constitutively expressed but switched on in response to the host environmental signals, often co regulated ie global regulation. 2 - often carried in extra chromosomal plasmids and/or grouped on pathogenicity islands in the chromosome. 3 - they encod proteins and other molecules that are exported to the bacterial cell surface or secreted or delivered into host cells

Question 4

how do bacteria colonise a host?

Answer 4

1. cell surface adhesins to attach to cells or ECM. typically on the tips of long rigid pili/fimbriae ie the P-pilus adhesin of uropathogenic E.coli which binds a kidney receptor

Question 5

most common type of UTI?

Answer 5

1. mostly by E.Coli from the host’s own colon flora by ascending infection. mainly in women due to shorter urethra and catheter use. motility aids ascent, common (type1) pili bind bladder cells. pap (p-pili) binds kidney receptors. damage is by pore-forming toxin (haemolysin) and inflammation (LPS). In proteus infections, urease cleaves urea to ammonia causing kidney stones.

Question 6

what do EPEC and EHEC stand for and what do they cause?

Answer 6

1. • enteropathic E.coli and enterohaemorrhagic E.coli which adhere to epithelial cells tighter than uropathogenic E.coli (UPEC) and cause intestinal disease. delivers proteins into the cell via specialized needles to including the translocated intimin receptor (TIR). bacterial surface intimin binds Tir, causes subversion of host cell signal transduction and promotes actin polymerisation to induce pedestal formation.

Question 7

• what are biofilms, examples?

Answer 7

1. complex structures formed by adherent bacteria. difficult to eradicate by immune system and antibiotics. streptococcus mutans forms plaque on teeth (and other bacteria). staphylococci colonise catheters. pseudomonas aeruginose colonise the lungs of cystic fibrosis patients.

Question 8

how do bacteria invade host cells?

Answer 8

1. • 2 mechanisms, both via cytoskeleton. 1 - zipper mechanism. receptor mediated endocytosis ie triggered by listeria. bacterial invasins mimic eukaryotic ligands. 2 - trigger mechanism - bacterial proteins delivered by needles, subvert and cause cytoskeletal rearrangment. effector proteins mimic host proteins (eg SipA and SipC) or can be homologues (SptP). salmoella uses this mechanism and has its effector genes on a pathogenicity environment (SPI-1).

Question 9

how do bacteria spread once they have infected?

Answer 9

some spread between epithelial cells by escaping the entry vacuole into cytosol, replicating and spreading to adjacent cells (shigella, listeria, rickettsia). some just replicate in their entry vacuole (salmonella). others survive in macrophages and spread via macrophage movement (salmonella typhi - typhoid). many extracellular bacterial use batteries of enzymes to digest connective tissue (collagenase, hyaluronidase) and blood clots (staphylokinase) and DNA in pus (DNAse) - (staphylococcus and streptococcus -pyogenic cocci.

Question 10

how do bacteria survive in the hostile environment of the host?

Answer 10

1. • iron is essential but is in low conc so virtually all will bind it with high affinity by secreting iron-binding molecules (siderophores?) and reimporting them once reloaded. the other variable is stomach acid, many can resist the low pH by pumping out protons or producing ammonia with urease (shigella - dysentery, helicobacter - ulcers).

Question 11

how do bacteria block macrophages endocytosing them?

Answer 11

1. 1 - paralyse the macrophage by injecting proteins to disrupt intracelluar trafficking and signal transduction. yersinia = Yopt, a protease to target small GTPases to disrupt cytoskeleton, YopP, an acetyl transferase that inhibits signalling to trigger apoptosis. 2- inhibit chemotaxis - cleave C5a with C5a peptidase. 3 - shield itself with antiphagocytic capsules, can be made of non-immunogenic polysaccharide eg sialic acid or lacking affinity for complement factor B so no C3b formation. ie streptococcus pneumoniae (pneumonia). 4 - secrete cytolysins to kill macrophages. these form pores, disrupt cell functions, cause apoptosis, destroy membrane integrity. eg Gram +ve Strep. pyogenes (streptolysin), Pneumococcus (pneumolysin), Gram -ve E.coli and B. pertussis (whooping cough).

Question 12

how do bacteria survive inside the macrophage?

Answer 12

1. • some inhibit phagosome-lysosome fusion ie salmonella and mycobacterium. others resist the oxidative burst.

Question 13

how do bacteria resist complement?

Answer 13

the LPS O antigen and capsules hinder access to the cell and hence prevent MAC formation.

Question 14

how do bacteria evade antibody recognition?

Answer 14

1. • 1 - mimic host (attach sialic acid to LPS o-antigen) 2 - shut off or switch expression of surface antigens by PHASE VARIATION (salmonella flagellin by DNA rearrangement) 3 - more complex DNA rearrangement to generate ANTIGENIC VARIATION (neisseria pilus (adhesion) genes, it has multiple types that are silent and can be switched in to the expression locus)

Question 15

what causes gonorrhoea?

Answer 15

neisseria gonorrhoea - a gram negative diplococci. the disease can follow different paths - acute urethritis may be followed by more severe complications. systemic spread - arthritis and endocarditis
-infertility following cervical infection
conjunctivitis and blindness in the newborn
a high incidence of infection is compounded by antibiotic resistance and asymptomatic carriers.

Question 16

how do bacteria inactivate antibody?

Answer 16

1 - secretory IgA is cleaved by proteases secreted by mucosal pathogens - strep. pneumoniae, haemophilus influenzae, neisseria gonorrhoea (gonococcus) and neisseria meningitidis (meningococcus)

2 - bacteris can bind the Fc of Ig and prevent opsonisation.