Thomas Proft Flashcards
What are some skin infections that can be caused by streptococcus pyogenes?
Cellulitis
Erysepelas
Impetigo
What is the immune response to bacterial infection of the skin?
Bacteria enters wound cause tissue damage (toxins and enzymes) -> platelets release blood clotting factors to contain the bacteria and prevent it from getting deeper -> Sentinel neutrophils and macrophages phagocytose bacteria -> macrophages release IL-8 and IL-6 that recruit leukocytes and induce chemotaxis -> Activate tissue repair
How are bacteria recognised by the innate immune cells?
PAMP are recognised by pattern recognition receptors, such as TLRs (TLR-4 and LPS). LPS is conserved on gram -ve bacteria.
This stimulation induces the activation of the innate cells and they secrete IL-1b, TNF-alpha and IL-8
How do leukocytes migrate through the endothelial cell wall?
E-selectin is upregulated on the endothelial cells
Selectin mediated adhesion to the leukocyte (E-selectin). This causes the leukocytes toroll and slow down. Then the integrins bind to integrins (LFA-1 to ICAM-1). Then they squeeze between the endothelial cells to enter the tissues. Then chemotaxis. (!L-8 and C5a)
What does C3b do?
Opsonisation
What does C5a do?
Chemotaxis
What are the defining features of streptococcus pyogenes?
Gram positive cocci.
Group A strep - agglutination by antibody
Catalase negative (no gas production when mixed with H2O2, some bacteria convert H2O2 into water and O2)
Beta haemolytic - can lyse blood cells
Bacitracin susceptibility
Transmission by human contact - touching, coughing
High infection rates in overcrowded houses.
What are the virulence factors of streptococcus pyogenes?
MSCRAMMS - microbial surface components recognizing adhesive matrix molecules. These bind to extracellular matrix proteins of host cells, such as collagen, fibronectin binding proteins
Hyaluronic acid capsule (prevents opsonisation and phagocytosis.
M protein - binds factor H, which prevents opsonisation with C3b
Secretion of toxins: streptolysins (lyse immune cells), C5a peptidase (destroys C5a), DNAses (degrades NETS).
SpyCEP - destroys IL-8
Proteases
Lipases
Hyaluronidase
Streptokinase - converts plasminogen to plasmin (anticoagulation)
What are the factors that allow streptococcus pyogenes to spread deeper into tissues?
Proteases
Lipases
Hyaluronidase
Streptokinase - converts plasminogen to plasmin (anticoagulation)
What does the catalase test check?
To see if the bacteria can convert H2O2 into water and O2.
What bacteria are alpha haemolytic bacteria?
Viridins bacteria.
What is the treatment for cellulitis?
If caused by S pyogenes then penicillin or a derrivative such as amoxycillin.
If S. Aureus then flucloxacillin (except for MRSA)
Give pain killer, rest elevation
How does penacillin work?
It binds to transpeptidase that links the peptidoglycans in the bacteria cell wall. Causes weak cell walls -> lysed.
What are two types of beta-lactam antibiotics?
Penicillins and cephalosporins
What are the different penicillins?
Benzylpenicillin is an IM injection
Amoxycillin is an oral form
How does osteomyelitis develop?
Bacteria get into the bone. This can occur from scratching (chickenpox) of the skin leading to infection that then gets into the bone.
Could also get to the bone from trauma (joint replacement, root canal), from Haematogenous route (bacteremia)
Once in the bone leukocytes can attak the bacteria causing inflammation. Bacteria may invade the bone cells to evade the immune system and drugs causing a chronic infection.
The bacteria can spread to the joint (septic arthritis)
Who are at risk of osteomyelitis?
Diabetics with foot ulcers Patients following trauma, bone surgery Intravenous drug users Root canal treatment Patients with skin and soft tissue infections.
What bacteria is the most common cause of osteomyelitis?
S Aureus. (80% of cases in those >4 yo)
S Pyogenes
What bones are infected in osteomyelitis?
Adults: Vertebral and hip replacement, foot, long bone,
Children: long bones mainly - tibia and femur
How can you diagnose osteomyelitis?
Symptoms of pain/weakness of specific bones, redness, fever.
Blood sample with high WBCs
Need an MRI to confirm the diagnosis
How does gram staining work?
Fix the slides -> cyrstal violet -> iodine (crystilises the dye trapping it in peptidoglycan) -> decolourisation -> counter stain with safranin.
Crystal violet gets trapped in the peptidoglycan in the gram positive bacteria
How do you identify stapylococcus aureus?
Gram positive Catalase positive (h2O2 -> H20 and O2)
Coagulase positive - converts fibrinogen in plasma into fibrin - coagulation
What is a coagulase negative bacteria?
Staphylococcus epidermitis
What are the virulence factors for S Aureus?
Adhesion molecules - MSCRAMS (microbial surface components recognizing adhesion matrix molecules. Binds to cells extra cellular matrix - collagen, fibronectin, laminin.
Spreading factors - staphylokinase causes fibrinolysis
Lipases - hydrolises lipids
DNAses - NET degredation
Cytolisins - destroys epithelial cells
Avoids immune cells:
Cytolysins to degrade WBCs
Capsule - prevents opsonisation and phagocytosis
Biofilm formation
Protein A: binds to the Fc region of antibodies
Cell bound coagulase (clumping factor) - fibrin deposition prevents phagocytosis and opsonisation
What are super antigens?
Produced by S aureus and S pyogenes
Proteins that induce a stong T cell imune response - IL-1b, TNF-alpha, IFN-y.
Causes systemic inflammation with tissue destruction, vascular leakage, toxic shock
What is used to treat MSRA?
Vanocomycin
How do you treat osteomyelitis?
Prolonged antibiotic treatment (weeks to months).
Determine the organism
How do some bacteria resist against penicillins?
They have beta lactamases enzymes (plasmid encoded enzyme) that degrades the beta lactam ring of penicillin.
There are now beta lactam resistant penicillins
What group of bacteria can penicillin target?
Gram positive bacteria.
Extended spectrum penicillins have been developed that can target gram negatives too, amoxycillin
What are some beta lactam resistant penicillins?
Methicillin (prototype), flucloxacillin
Augmentin = amoxycillin + clavulanic acid
How does MRSA occur?
They have acquired a new transpeptidase enzyme. No binding for any penicillins.
What resistance to penicillin does normal S aureus have?
Beta lactamase that degrades penicillins beta lactam ring.
What are some other disease caused by S aureus?
Impetigo Folliculitis Furuncle Carbuncle Cellulitis Necrotizing fascitis Septic arthritis Acute infectious endocarditis Bacterial pneumonia Toxic shock - menstrual toxic shock from tampons
