Lecture 1: Streptococci, Enterococcus, Pneumococcus and Staphylococcus Flashcards
Who was streptococci first described by?
Luis Pasteur in 1879 by observing puerperal fever (childbed fever) in maternity ward patients
- it was one of the first microbes identified as causing contagious disease (germ theory)
- it’s discovery lead to hygiene and aseptic practices in hospital wards.
- there are over 100 recognized species of streptococcus
What was streptococcus originally classified into?
Lancefield groups
- serological classification based on major cell-wall carbohydrate antigens (Groups A-H)
- many strep are untypeable - no antisera reacts to their cell wall antigens
- work well for pyogenic strep
What are the lancefield groups of streptococci?
Group A - streptococcus pyogenes (pus)
Group B - streptococcus agalactiae
What are streptococci?
- gram positive cocci arranged in chain
- are smaller and more ovoid than staphylococci
- catalase negative
- non-spore forming
- non-motile (no flagella)
- capsule (is variable)
- can be made of carbohydrate or hyaluronic acid
What is streptococcus classification based on?
it’s based on hemolysis on blood agar
Hemolysis pattern:
- alpha partial hemolysis and green discoloration of hemoglobin (viridans strep mostly in oral cavity)
- beta clear zone of complete hemolysis (GBS and GAS)
- gamma no zone of clearing
Species Level classification:
- biochemical reactions look for particular enzymes
- DNA sequence based on 16S rRNA is also used
What are the diseases caused by S. pyogenes?
This is a Group A Strep (GAS) - meaning it exclusively infects humans
Types of GAS infections (primarily infects respiratory tract, bloodstream, and skin):
1) Suppurative (pus) disease: caused by direct damage by the organism
2) toxin-mediated disease: systemic response caused by streptococcal exotoxins secreted in bloodstream.
3) non-suppurative sequelea (bold): late manifestations -autoimmune - aberrant immunological reaction to GAS antigens
**Spread by respiratory drops and direct person to person contact (scarlet fever and toxic shock syndrome)
What are the virulence factors of S. pyogenes (what does this bacteria have that allows it to be so virulent)?
- genomes of disease isolates are >90% identical and differ only in the phage they carry
- M protein: adhesin binds to keratinocytes (outer layer of skin)
- protein F: fibronectin binding protein (is an adhesin)
- hyaluronic acid (HA) capsule: anti-phagocytic
- hyaluronidase (spreading factor): allows S. progenies to spread through tissues
- C5a peptidase: degrades complement protein C5a-blocking phagocyte chemotaxis
- streptolysin S and O: hemolysis that lyse various host cells (is an invasin)
- streptokinase: binds human plasminogen converting it to plasmin- breaks fibrin clots allowing tissue spread (is an invasin)
- pyrogenic exotoxins - superantigens: fever, neutropenia, rash of scarlet fever
What is the pathogenesis of GAS infection (what identifies as a GAS infection)?
Adherence to mucosal surfaces (fibronectin) by:
- pili, M protein, LTA and Protein F
Adherence to sub corneal keratinocytes (epidermis) by:
- M protein and protein F
Invasion of non-phagocytic cells occurs but is not completely understood.
Once past host barriers, GAS secrete virulence factors which allow host immune evasion and deeper infections to be established.
**streptococcus progenies owes its major success as a pathogen to it’s ability to colonize and rapidly multiply and spread in its host while evading phagocytosis and confusing the immune system
What’s S. pyogenes M protein?
Resembles myosin (has a coiled structure) - function:
a) binds to keratinocytes
b) prevents opsonization (phagocytosis) by complement
Antibodies against hypervariable region (called this because it’s variable within different strains) (A) can opsonize, but:
- >200 distinct M protein serotypes are responsible for subtypes of GAS- immunity to one serotype doesn’t confer protection to others.
-Type-specific opsonic epitopes: type specific AB
-semi-conserved epitopes: binds fibrinogen
-high conserved epitopes: serum factor H
M protein type determines disease GAS can cause
some M protein epitopes resemble host heart muscle - rheumatogenic strains where the host produces cross-reactive antibodies
Complement pathway refresher
S. pyogenes:
- M proteins - binds fibrinogen, which prevents binding of C3b
- M protein - binds complement control. protein Factor H inhibits alternative complement pathway
- C5a petidase - degrades C5a - peptide mediator of inflammation (prevents chemotaxis)
What’s the complement pathway?
The complement system is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen’s cell membrane
What are the functional protein classes in the complement system?
1) proteins that bind to pathogens- start the process
2) proteolysis of complement proteins to activate enzymes
3) bind to pathogens
4) inflammation - recruit neutrophils to infection and activate macorphages
5) poke holes in bacterial cells
6) found on phagocytes - bind to pathogens with complement proteins
7) serum proteins that regulate complement cascade
What is the hyaluronic acid (HA) capsules?
- purpose: antiphagocytic structure
- camouflage against the immune system non-antigenic
- HA is found in connective tissue
- however, capsule interferes with adherence to epithelial cells
- secreted hyaluronidase digests the capsule, following S. pyogenes to spread through tissue
What are streptolysin S and O?
-is a pore forming toxin that can:
* lyse red blood (hemolysin) cells (beta hemolysis on blood agar)
* kill phagocytes (leukocidin)
* lyse various host cells to release nutrients for growth
The 2 forms are:
- streptolysin S (SLS) - O2 - stable
- streptolysin O (SLO) - O2 - labile - doesn’t work w/ O2
