Pathogens 1 Gram +ve cocci - staphylococcus/streptococcus

explain the general prokaryote structure

P,N,R,CW

plasmids: carry genes, free circular structure

nucleoid: single, non-membrane loop of DNA

70s ribosomes: 30s+50s subunits

cell wall: protection from osmotic lysis

what is the structure of bacterial cell wall

• repeating units of NAG, NAM, NAG, NAM = peptidoglycan

• these layers are cross linked with PBPs that bind to D-Ala(penicillin binding proteins)

what are the four stages to infection: EAIT

1. Exposure – pathogens encounter host tissues 

2. Adhesion – receptors on pathogen bind to target on cells 

3. Invasion – secreted invasins break through tissue/ cells OR pathogens enter/ engulfed by host cells OR organisms enter through damaged tissues  

4. Toxicity – pathogens replicate and begin to cause tissue destruction/ dysfunction 

give teh order of skin infections superficial to deep, which layers it involves

1. Impetigo – epidermis 

2. Cellulitis – dermis 

3. Fasciitis, osteomyelitis – hypodermis  

with soft tissue infections how can each gram +ve cocci adhere to damaged cells 1,3

Skin trauma allows entry of bacteria below stratum basale  

Staphylococcus species: 

• These have MSCRAMM to bind to the matrix protein on damaged cells 

Group A streptococcus: GAS

• These have F-protein and opacity factor (OF) that bind to fibronectin on damaged cells 

• ADHESINS = proteins on the surface of bacteria that facilitate colonisation and infection 

• The expression of ADHESINS allow for tight binding of bacteria 

• Tight binding prevents expulsion by blood flow out of wounds 

• MSCRAMM = microbial surface- recognising adhesive matrix molecules 

once adhesion is achieved what is now possible for the bacteria

• what do local cells now detect

• what do epithelial cells now secrete

• what cytokines are released in response

Adhesion leads to replication of bacteria and colonisation of the local area 

• TLRs on local cells detect lipoteichoic acids in bacterial cell wall 

• Epithelial cells secrete beta-defensins to kill bacteria  

• pro-inflammatory cytokines, TNF-a, IL1B, IL-6

what are the benefits of early recognition

• effect of TNF-a

• C3b

• what 2 things do phagocytes do

Early recognition leads to very localised inflammation and cytokine production 

• TNFa drives local NO production to cause vasodilation 

• Neutrophils are recruited from circulation  

• Acute phase proteins are recruited C3, C3b  

• Bacteria rapidly accumulate complement (C3b) 

Rapid clearance of bacteria with no/ little effects on the host  

• Accumulated C3b is recognised by complement receptors  

• Phagocytes detect and clear pathogens before driving tissue repair

how do bacteria evade the IS during soft tissue infections

• which layer do they reach

• what do they secrete

• what can spread lead to

• Bacteria enter upper layers of the skin beyond easy reach of immune cells (above stratum basale) 

• Bacteria secrete MMPs (protein enzymes) to kill defensins while epithelial cells secrete beta-defensins to kill bacteria 

• Spread can lead to impetigo 

what protein does Group A streptococcus have that allows it to evade the IS

• where is the protein located

• what does it bind to

• GAS have M-proteins in their cell walls and they block complement from binding to make it not recognisable by phagocytes

• The lack of complement driven opsonisation prevents clearance of bacteria by macrophages  

how does S.aureus and GAS evade the IS, what does it block (2)

they produce a polysaccharide capsule that resists complement binding and avoids recognition by phagocytes

The lack of complement driven opsonisation prevents clearance of bacteria by macrophages  

what is COAGULASE

Coagulase, also clumping factor is a specific example of preventing host immune recognition

whats the difference between coagulase -ve and +ve staphylococci:

+ve

• what does it activate on host cells

• what does this produce and bind to

• what is this converted to and block

Coagulase negative staphylococci: 

• Rapidly detected by immune cells and cleared 

Coagulase positive staphylococci: (S.aureus) 

• Produce coagulase bound to their surface which binds inactive host prothrombin 

• Prothrombin activated -> thrombin 

• Thrombin binds soluble fibrinogen to the surface of the bacteria  

• Fibrinogen is converted to insoluble fibrin and forms a net of host molecules  

• These block the recognition by immune cells  

what enzyme do both GAS and S.aureus produce

• what does it do

• Staphylococcus aureus and GAS both produce HYALURONIDASE  

• Hyaluronidase degrades ECM and allows bacteria to escape from tissues  

what is the NET by neutrophils

• what two things stimulate this (cytokine, T cell type)

• what enzyme does GAS/S.aureus produce to break this down

NET= neutrophil extracellular trap, when neutrophil releases DNA and proteins to trap pathogens

• TNFa and Th17 stimulated neutrophils deploy NETs (neutrophil extracellular traps) 

• s.aureus and GAS produce DNAses which degrades DNA and NET destroyed 

what is streptokinase in relation to coagulase

le opposite

how does streptokinase work

• why is it needed for bacteria

• what does streptokinase +ve GAS cleave

• what does plasmin do to help bacteria

• Bacteria is trapped by coagulated blood  

• Streptokinase positive GAS cleave regulatory sequences on tissue plasminogen which activates to plasmin 

• The plasmin degrades fibrin clots and releases bacteria  

• Bacteria escapes from clots and spreads  

what is the significance of protein A

• what class of antibody accumulates and gets pathogens detected

• what receptor do phagocytes have to detect these antibodies

• which gram pos cocci produces protein A, a modified …

• what does it bind to

• what is the effect of them binding

• Pathogens accumulate IgG and are cleared by recruited phagocytes 

• Phagocytes have FcyRI receptors that detect bound IgG  

• S.aureus can produce protein A – a modified adhesin 

• Protein A binds Fc portion of IgG and inverts the antibody  

• IgG cannot be detected by FcyRI receptors and pathogen isnt cleared  

what harmful chemical can GAS, S.aureus secrete

they can secrete haemolysins which can form pores in RBC, virulence factor