Streptcoccus pyogenes Flashcards
Define normal flora of the mouth and URT
The normal flora of the respiratory tract can also be termed the commensal microflora.
Note that humans have 10 fold more bacterial cells than human cells.
**Commensal microflora inhabit the skin and mucous membranes ^[is in continuity with outside environment].
The normal flora is defined as the population of micro-organisms found growing routinely on the body of a healthy individual ^[associated with good health, e.g. autoimmune diseases, T2D, response to cancer etc. Diverse].
There are two main types of commensal flora:
- resident flora: which inhabits body sites for extended periods of time, and re-establishes if it is disturbed
- transient flora: which inhabits body sites for short periods of time e.g. hours, days, weeks
Normal flora of the respiratory tract:
- can be divided into normal flora of teeth, mouth, throat and nose (see also [[Anatomy Lecture 8]] and [[Anatomy Lecture 11]])
- knowledge of the normal flora is important when interpreting the significance of microbiological culture results ^[to distinguish between flora that is pathogenic or can become pathogenic – need to integrate information from history and patient symptoms with clinical report]
- knowledge of normal flora, and which bacteria may become pathogenic, can also help to guide antibiotic treatment
Normal flora of the teeth and mouth
- The normal or commensal flora of the teeth and mouth are predominantly anaerobic bacteria (e.g. Bacteriodies, S. mutans, F. streptococci, actinomyces, Streptococci, S.viridans, and Candida sp. - a yeast, see [[Microbiology Lecture 1]])
- infections are related to teeth (e.g. gingivitis and tooth abscesses) as well as deep soft tissue of the neck ^[e.g. can go up to brain, cause abscess]
- oral thrush usually occurs when antibiotics reduce normal bacterial flora - leading to overgrowth of Candida sp.
- some disseminate and cause infections elsewhere e.g. infective endocarditis, liver abscesses, infection of heart valves e.g. rheumatic fever
e.g. dental plaque, biofilm ([[Microbiology Lecture 4]])
Normal flora of the throat
Examples of normal flora found in the throat include S. pneumoniae, S. viridans, S.pyogenes, Neisseria spp. esp Neisseria meningitidis, and Haemophilus influenzae.
- some throat flora e.g. S. pyogenes cause pharyngitis
- others spread locally causing sinusitis, otitis media and/or pneumonia ^[e.g. when aspirated]
- Streptococcus pneumoniae
- H. influenzae
- S. aureus
- some can disseminate causing bacteremia, and/or meningitis
- S. pneumoniae
- H. influenzae
- N. meningitidis
Why is it important to distinguish between normal and pathogenic flora?
Normal flora of the respiratory tract:
- can be divided into normal flora of teeth, mouth, throat and nose (see also [[Anatomy Lecture 8]] and [[Anatomy Lecture 11]])
- knowledge of the normal flora is important when interpreting the significance of microbiological culture results ^[to distinguish between flora that is pathogenic or can become pathogenic – need to integrate information from history and patient symptoms with clinical report]
- knowledge of normal flora, and which bacteria may become pathogenic, can also help to guide antibiotic treatment
Define and distinguish between resident and transient flora
There are two main types of commensal flora:
- resident flora: which inhabits body sites for extended periods of time, and re-establishes if it is disturbed
- transient flora: which inhabits body sites for short periods of time e.g. hours, days, weeks
Provide examples of normal flora of teeth and mouth, and some examples of disease
The normal or commensal flora of the teeth and mouth are predominantly anaerobic bacteria (e.g. Bacteriodies, S. mutans, F. streptococci, actinomyces, Streptococci, S.viridans, and Candida sp. - a yeast, see [[Microbiology Lecture 1]])
- infections are related to teeth (e.g. gingivitis and tooth abscesses) as well as deep soft tissue of the neck ^[e.g. can go up to brain, cause abscess]
- oral thrush usually occurs when antibiotics reduce normal bacterial flora - leading to overgrowth of Candida sp.
- some disseminate and cause infections elsewhere e.g. infective endocarditis, liver abscesses, infection of heart valves e.g. rheumatic fever
e.g. dental plaque, biofilm
Provide examples of normal flora of the throat and some diseases
Examples of normal flora found in the throat include S. pneumoniae, S. viridans, S.pyogenes, Neisseria spp. esp Neisseria meningitidis, and Haemophilus influenzae.
- some throat flora e.g. S. pyogenes cause pharyngitis
- others spread locally causing sinusitis, otitis media and/or pneumonia ^[e.g. when aspirated]
- Streptococcus pneumoniae
- H. influenzae
- S. aureus
- some can disseminate causing bacteremia, and/or meningitis
- S. pneumoniae
- H. influenzae
- N. meningitidis
- S. pyogenes (can also cause meningitis)
Define and distinguish between commensals and pathogens
Commensal microflora inhabit the skin and mucous membranes.
They can be divided into two types: resident and transient flora (see above).
Pathogens, or disease-causing bacteria, can also be divided into two types:
- endogenous
- part of the resident or transient normal flors
- example Streptococcus pyogenes
- they can be considered pathogenic when they enter areas of the body where they are not meant to be (i.e. opportunistic infections) ^[[[Microbiology Lecture 4]]]
- pathogenicity is related to host factors, such as:
- immunity e.g. drugs, neonates, other medical conditions
- disruption to normal protective barrier, e.g. a cut to the skin
- exogenous
- exogenous flora are not considered normal or commensal flora
- if isolated, it is considered pathogenic (link back to Koch’s postulates, see also [[Microbiology Lecture 1]])
- examples of exogenous bacteria include Mycobacterium tuberculosis and Neisseria gonorrhoeae
Describe the morphology of Streptococcus sp.
Streptococcus sp. are gram positive.
They are cocci, either found in long chains, or in short chains i.e. diplococci.
Streptococcal species are facultative anaerobes.
For revision:
- strict anaerobe only grows with **oxygen
- strict anaerobe only grows without oxygen
- facultative anaerobe can grow with or without oxygen
Describe how Strep sp. are categorised
The Streptococcaceae family can be divided into 3 genera:
- Lactococcus
- Pediococcus
- Streptococcus
Lactococcus and Pediococcus are rarely medically important.
Streptococcus contains 68 species, 10 that infect humans. The 68 species are including those that are clinically significant.
Classification of Streptococcus species
- morphological - culture appearance - haemolysis ^[Hemolysis (from Greek αιμόλυση, meaning ‘blood breakdown’) is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms]
- beta haemolysis (complete RBC lysis, resulting in yellow appearance, due to streptolysin):
- Strep. pyognenes
- Strep. agalactiae
- Group C and G Streptococcus - S. dysgalactiae
- Some Strep. milleri
- alpha haemolysis (light and greenish agar, caused by H2O2 produced by bacterium, oxidising haemoglobin to yield methemoglobin):
- Strep. viridans
- Strep. pnuemoniae
- Some Strep. milleri
- Some Strep. bovis
- gamma haemolysis (no haemolysis):
- Strep. bovis
- Some Strep. viridans - cell wall characteristics - Lancefield grouping, a serological method - A ^[clinically may be referred to as G= group A Strep, i.e. GAS ] - Streptococcus pyogenes
- A group cause diseases such as pharyngitis, skin infections, puerperal sepsis - B - Streptococcus agalactiae (b-haemo)
- neonatal sepsis, puerperal sepsis ^[aka maternal sepsis], cellulitis - C/G - Streptococcus dysgalactiae (b-haem) - similar presentation to Group As
- pharyngitis, skin infections ^[zoonotic] - C/G/F/non-typable - Streptococcus milleri (could be A/B/gamma)
- abscesses - brain, lungs, abdominal ^[forms abscesses typically in association with other anaerobes] - D - Streptococcus bovis (Enterococcus species)
- bowel related infections, endocarditis - Non-typable - S. pneumoniae and S. viridans type
- meningitis, pneumonia, bacteraemia; often contaminants in blood, endocarditis ^[also S.aureus. Entero and Strep associated with HAI endocarditis] - measured by latex agglutination ^[Agglutination is the process that occurs when an antigen is mixed with its corresponding antibody called agglutinin and is commonly used in blood grouping](https://www.lornelabs.com/products/blood-transfusion/blood-grouping-reagents). ; Latex agglutination tests can be taken by collecting a sample containing the specific antigen, or antibody, which is later mixed with an antibody, or antigen, which is coated on latex beads in serial dilutions with normal saline. If the suspected substance is present, the latex beads will clump together, i.e. a positive test. This clumping is called agglutination. No agglutination = negative test] - metabolic activities- this requires growth of the pathogen overnight, so it takes ~12 hours to get a result - mass spectrometry e.g. MALDI-TOF - this is a cheap and fast (0.5h) technique
- administer small amount of organism on metal slide (via MALDI technique)
- matrix stabilises
- target with laser, separates the organism, captured by detector, generates a spectrum, mapped to a a database --> identifies the pathogen
- more details than Lancefield, i.e. species vs. Groups
Briefly describe the MALDI-TOF technique and its advantages
mass spectrometry e.g. MALDI-TOF - this is a cheap and fast (0.5h) technique
- administer small amount of organism on metal slide (via MALDI technique)
- matrix stabilises
- target with laser, separates the organism, captured by detector, generates a spectrum, mapped to a a database –> identifies the pathogen
- more details than Lancefield, i.e. species vs. Groups
commonly adopted now in micro/path labs
Describe the process of testing for Lancefield groupings
measured by latex agglutination ^Agglutination is the process that occurs when an antigen is mixed with its corresponding antibody called agglutinin and is commonly used in blood grouping. ; Latex agglutination tests can be taken by collecting a sample containing the specific antigen, or antibody, which is later mixed with an antibody, or antigen, which is coated on latex beads in serial dilutions with normal saline. If the suspected substance is present, the latex beads will clump together, i.e. a positive test. This clumping is called agglutination. No agglutination = negative test]
List and describe the virulence factors of S. pyogenes
Streptococcus pyogenes is a group A bacterium, and is beta haemolytic.
The prefix “pyus” refers to pus, as this organism is usually involved in pus-producing, or pyogenic, infections.
Streptococcus pyogenes is considered both a model commensal and endogenous pathogen.
S. pyogenes is a member of the commensal flora of some healthy individuals in the throat and skin - thus is an endogenous pathogen at these two locations.
There are several virulence factors of bacterial pathogens, these include (revise [[Microbiology Lecture 1]], and [[Microbiology Lecture 4]]):
- adhesin. Adhesion coordinates the binding of the organism to a host tissue. It is involved in the first of a series of events during infection: adherence to epithelium, through multiple factors, and beginning replication (producing aggressins that mediate damage)
- examples of adhesins include fibronectin-binding proteins, and lipoteichoic acid ([[Microbiology Lecture 4]])
-
- invasin
- impedin - evasion of the immune response
- recall the components of the innate immune response: complement activation - which marks foreign particles for opsonisation and assists in phagocytosis
- S.pyogenes evades complement activation by inhibiting the alternate complement pathways using the M protein, and a C5a peptidase to prevent neutrophil recruitment
- aggressin - S.pyogees produces many enzymes that promote tissue destruction, and dissemination:
- hyaluronidase: cleaves human hyaluronan in epithelial and connective tissue
- streptokinase: contributes to lysis of clots to facilitate dissemination — and is the initial agent used to treat AMIs
- DNAses - degrade DNA in pus, reduces viscosity, and contributes to spread.
- note: patient antibodies against DNAse B are an important marker of S.pyogenes infection – particularly in soft tissue or skin infections
- Streptolysins O and S are cytotoxic to a number of cells, including RBCs, and are involved in beta haemolysis
- SpeB, a cysteine protease that destrous a number of human proteins
The determinant of S. pyogenes serotypes is the hypervariable region of the NTD of the M protein, which emanates from the capsule and extends out towards the extracellular environment.
- There are over 100 M protein types ^[note that it is not usually tested for in a clinical setting, but it is becoming more an option in public health]
- Specific M types are associated with specific infections: some M types cause more invasive or serious disease ^[e.g. waves of severe S.pyogenes - more virulent but less c, therefore more prone]
- antibody against the M protein is protective ^[hence an interest in developing a vaccine, different M types need to be targeted in a vaccine]
Note: M protein is involved in other functions:
- as an adhesin, it may be involved in adhesion, therefore initiating the infection (i.e. successful multiplication of organism within the host, occurs when microbe enters – but may or may not be successful, see also [[Microbiology Lecture 4]])
- it may also be involved in mediating immune reactions, as a modulin. Examples include immune reactions in rheumatic fever and glomerulonephritis
- it may also act as an impedin, preventing complement activation and subsequent opsonisation. See also [[Immunology Lecture 2]] and [[Immunology Lecture 3]]
Describe bacterial capsules role in S. pyogenes infection
Bacterial capsules ([[Microbiology Lecture 3]] and [[Microbiology Lecture 4]]):
Some strains of S.pyogenes have a capsule composed of hyaluronic acid.
This hyaluronic acid is similar to that found in human connection tissue.
Thus S. pyogenes evades the immune response by masquerading as self…an example of an impedin
Note: capsules can define “serotypes” of encapsulated bacteria such as Strep. pneumoniae, but not in the case of S. pyogenes ^[why?].
Describe the immune response to S. pyogenes infection
Focus on components of the innate response: (see also [[Immunology Lecture 1]], [[Immunology Lecture 2]], [[Immunology Lecture 6]]- last one re: residents)
- complement activation
- phagocytosis
- tissue macrophages - live in tissues, and work from beginning to end, phagocytose bacteria, raise the alarm i.e. cytokines, and have additional functions
- neutrophils or PMNS - short lived, dedicated killers of bacteria, recruited from blood
Steps of phagocytosis include
1. the binding of the pathogen to phagocyte. This can occur:
- indrectly i.e. antibody medaed. Complement mediated following activation(phagocyte receptors bind to activated complement bound to the bacteria)
- directly o.e. Macrophage cell surface receptors or pattern recognition receptors (PRRs), bind to bacterial targets or pathogen associated molecular patterns (PAMPs) – masked by capsules
- examples of gram positive PAMPs include peptidoglycan and lipoteichoic acid
2. internalisation of pathogen in phagosome
3. fusion of phagosome with lysosome, which contains antimicrobial factors ([[Cell Biology Lecture 3]])
4. microbial death
List immune mediated diseases associated with S. pyogenes infection
Immune mediated disease i.e. disease that has deleterious effect on host
- rheumatic fever ^[mainly affects Aboriginal and Torres Strait Islander in remote areas; only prevalent in Maori and Pasifika communities; also North and s-Saharan, Latin Am., Indian Sub.c. side note: Egypt has high death rate]
- group A streptococcus
- results in inflammatory changes in heat, joints, blood vessels and subcutaneous tissues
- M protein mimics the heart muscle, such that M protein antibodies cross react with tthe heart and damage the heart
- glomerulonephritis
- immune complex deposition in glomeruli
Desribe local or systemic disease associated with S. pyogenes infection
● Pharyngitis
● Skin infections
● Disseminated infections eg bacteraemia, post partum sepsis
