Gram positive cocci Flashcards

1
Q

Aerobic gram positive bacteria can be of 2 shapes, which are they?

A

Either bacilli or cocci

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2
Q

How are the gram-positive cocci further categorised?

A

Via the catalase test, they can either be catalase-positive, in which case they are the staphylococcus

Or they can be catalase-negative, in which case they are the streptococci

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3
Q

What is the catalase reaction?

A

catalase is an enzyme produced by the bacteria, and this enzyme catalyses the reaction of Hydrogen Peroxide to Water & Oxygen

H2O2 –>

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4
Q

Then, which test is used to differentiate amongst the bacteria within the staphylococcus?

A

The coagulase test is used

Coagulase positive = S. aureus

Coagulase negative = CoNS (coagulase negative staplococcus)

like the S. epidermidis

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5
Q

How is the coagulase test performed?

A

A loop of S. aureus is taken, it is inoculated in plasma and incubated

The S. aureus produces a coagulase enzyme which coagulates the plasma (it becomes gloopy)

In coagulase-negative staphylococci, the plasma is not coagulated and can be spread

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6
Q

Which organisms are the coagulase-negative staphylococci?

A

CoNS are usually found on humans, as members of the normal skin flora

These are commensal, beneficial organisms

Like the S. epidermidis

These have low virulence but can be pathogenic in some settings (eg. when the skin barrier has been breached, in immunocompromised individuals (premature kids)

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7
Q

How is the streptococcus differentiated?

A

By haemolysis into the alpha, beta and gamma groups

alpha = S. pneumoniae (viridans group)

beta = S. pyogenes and S. agalactiae

Classified by the way they haemolyse blood agar
Beta = blood is dissolved, agar is transparent

Alpha = partial haemolysis, agar has olive-green tinge

Gamma = no haemolysis

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8
Q

S. aureus - where does it infect?

how common/important is it?

A

It is an important human pathogen
20 - 40% of the population are carriers
It infects the anterior nares, axilla and groin regions
It likes warm, moist areas

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9
Q

What types of infections does S. aureus cause?

A

It can cause localised or disseminated infections
it is pyogenic (pus-forming), eg. abscess infections in almost any organ

An abscess is a central area of pus, which is walled off by fibrous material

The coagulase enzyme S. aureus produces assists in causing coagulation and fibrin around the site of infection, which walls off the centre of infection

The coagulase toxin walls off the infection, whilst lytic toxins like hemolysins and proteases destroy the host tissue

There is an invasion of neutrophils, hence, pus forms in the middle

There is a fibrous wall which surrounds it, by the coagulase enzyme which walls off the infection.

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9
Q

What types of infections does S. aureus cause?

A

It can cause localised or disseminated infections
it is pyogenic (pus-forming), eg. abscess infections in almost any organ

An abscess is a central area of pus, which is walled off by fibrous material

The coagulase enzyme S. aureus produces assists in causing coagulation and fibrin around the site of infection, which walls off the centre of infection

The coagulase toxin walls off the infection, whilst lytic toxins like hemolysins and proteases destroy the host tissue

There is an invasion of neutrophils, hence, pus forms in the middle

There is a fibrous wall which surrounds it, by the coagulase enzyme which walls off the infection.

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10
Q

S. aureus colonization vs disease

What determines whether S. aureus is simply going to colonise, or if it is going to proceed into an invasive disease?

A

Quorum sensing is chemical communication between groups of bacteria that is dependent on the surrounding environmental conditions, including bacterial density (number of bacteria at a site)

This communication influences bacterial behaviour, allowing bacteria to collaborate in response to environmental conditions

The quorum-sensing system in S. aureus works through the Agr (accessory gene regulator)

Agr contributes to S. aureus pathogenicity in several infection types
including subcutaneous abscesses, endocarditis and arthritis

Endocarditis is caused by bacteria in the bloodstream multiplying and spreading across the inner lining of your heart (endocardium).

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11
Q

What is the staphylococcal quorum-sensing system

A

The agr-sensing system is an auto-activating circuit which works through cell signalling

When the population density is low, the expression of virulence factor genes is repressed, but when the population density increases, the quorum-sensing signal transduction represses the repressor of the virulence factor genes, leading to increased expression of virulence factors, and an increase in infection and pathogenicity.

Each bacterial cell secretes a small protein called AIP
Each bacterial cell also expresses the receptor for the AIP molecule on its cell membrane called AgrC
AIP binds to Agr C and the receptor phosphorylates and activates an intracellular molecule called AgrA, which is a transcription factor, which when activated, induces the expression of the quorum-sensing system in a positive feedback loop (it activates transcription of P2 and P3 (Agr promoters, which drive the autoactivation circuit)
P3 drives the transcription of RNAIII, which enhances the promotion of virulence factors (increase in exotoxin production)
AgrA represses the repressor of virulence factor genes (self-activating), positive feedback loop, strengthens the quorum sensing mechanism itself and amplifies the response

Also activates the expression of genes that encode the individual components of the quorum-sensing mechanism
AgrD encodes the AIP peptide
AgrB encodes the transport protein responsible for AIP secretion
AgrC which is the receptor, that gets activated by AIP binding to it
And the gene encoding AgrA

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12
Q

Staphlococcus aureus infections

A

S. aureus is a frequent cause of skin infections
like:

folliculitis
furuncles (boils)
carbuncles 
impetigo 
cellulitis
wound infections

Other localised infections include lung abscess, brain abscess and mastitis (infection of the breast tissue in breastfeeding mothers –> often leading to premature cessation of breast feeding)

May also cause disseminated infection - including septicaemia
Where S. aureus circulates in the bloodstream
May progress to infection of a heart valve (endocarditis) which can be very destructive

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13
Q

S. aureus produces particular toxins (superantigens) which cause disease…

A

Causes non-pyogenic (non pus-forming disease) disease caused by toxins

Like SSS staphylococcal scalded skin syndrome

STSS staphylococcus toxic shock syndrome

Staphylococcal food poisoning

These diseases are caused by an enterotoxin, which is a superantigen (this gene originated in a bacteriophage, and was genetically transferred via transduction (horizontal gene transfer)

Superantigens bypass the normal antigen presentation, by directly crosslinking the T cell receptor and the MHC class II

this causes polyclonal activation of T cells hence, stimulation of a very strong and non-specific immune response

The toxin acts on the basal layer of the epidermis, and causes lysis
The superficial layers of the skin all shed off

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14
Q

How are the beta haemolytic streptococci further classified?

A

According to antigenic differences in their cell wall carbohydrates

20 different groups in the lancefield grouping system

Lancefield group A = Strep A
AKA Streptococcus pyogenes

Lancefield group B = Strep B
AKA Streptococcus agalactiae

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14
Q

How are the beta haemolytic streptococci further classified?

A

According to antigenic differences in their cell wall carbohydrates

20 different groups in the lancefield grouping system

Lancefield group A = Strep A
AKA Streptococcus pyogenes

Lancefield group B = Strep B
AKA Streptococcus agalactiae

15
Q

Streptococcus pyogenes (Lancefield group A) Beta haemolytic streptococcus infections

A

Causes primary infection
1) Throat (pharyngitis or tonsilitis)
Leading to abscess formation
Local extension to the sinuses, mastoid

2) Skin (cellulitis or impetigo)
Necrotizing fasciitis –> suppurative complications (an infection where there is pus formation)

Strep A is the most common bacterial cause of pharyngitis/tonsilitis (strep throat)

Peritonsillar abcess (quinsy)

The primary infection of the throat or skin can also lead to non-supparative complications (non-pyogenic)

Like acute rheumatic fever, and acute glomerulonephritis

Acute rheumatic fever can progress to cause rheumatic heart disease (rare but severe consequence with arthritis, rash, carditis (damage to heart valves & muscle), and writhing movements)

Can cause chronic narrowing or stiffness of the heart valves

These are immunological consequences of infections (misdirected immune response)

The peptides produced by strep pyogenes are very similar to the proteins found in the human tissue, particularly the heart tissue

then can get cross-reactivity (T and B cells that are meant to be directed against S. pyogenes, instead attack the heart tissue because of antigenic similarities) This inflammatory response in the heart tissue damages the heat

16
Q

Where are the alpha haemolytic streptococci found?

A

They are common commensals of the oropharynx, nasopharynx, gut and the genital tract

There are 2 groups of alpha haemolytic streptococci

1) viridans group (includes the step mutans)
2) streptococcus pneumoniae

16
Q

Where are the alpha haemolytic streptococci found?

A

They are common commensals of the oropharynx, nasopharynx, gut and the genital tract

There are 2 groups of alpha haemolytic streptococci

1) viridans group (includes the step mutans)
2) streptococcus pneumoniae

17
Q

What is the pathogenesis of dental caries

A

The continued intake of sucrose by the host, leads to ecological shifts in the oral microbiome that favour the growth of S. mutans

S. mutans secrete glycosyltransferases (GTFs), which stick onto the enamel

GTFs catabolise the sucrose, to produce large amounts of glucans which contribute to the build up of an extracellular polysaccharide matrix, which serves as a scaffold for biofilm (this is a scaffold where other bacteria can also lodge and grow)

when GTFs catabolise the sucrose, then organic acids like lactic acid are produced which decrease the pH, the low pH leads to the demineralisation of the enamel and initiates the carious process.

Streptococci acquired the gtf gene via horizontal gene transfer with lactic acid bacilli

The selective pressure of eating sugar resulted in the selection for streptococcal strains with multiple copies of the GTF gene

18
Q

Streptococcus pneumoniae: the pneumococcus

A

leading cause of pneumonia, and important cause of child death outside neonatal period

can cause meningitis as well

is a gram positive diplococcus

It has a polysaccharide capsule
there have been more than 94 capsular types identified till now but each binds to different antibodies of different specificities

the big, thick capsule is an important pathogenic factor for invasive disease as it prevents phagocytosis

Immunity against pneumococcus capsular type 1 - won’t protect against infection with capsular type 2 or 9 etc.

Challenge in vaccine development (can’t develop 94+ vaccines specific to each capsular type)

Hence, people take the most common capsular serotypes which are responsible for the most invasive disease, and create a vaccine that combines them

18
Q

Streptococcus pneumoniae: the pneumococcus

A

leading cause of pneumonia, and important cause of child death outside neonatal period

can cause meningitis as well

is a gram positive diplococcus

It has a polysaccharide capsule
there have been more than 94 capsular types identified till now but each binds to different antibodies of different specificities

the big, thick capsule is an important pathogenic factor for invasive disease as it prevents phagocytosis

Immunity against pneumococcus capsular type 1 - won’t protect against infection with capsular type 2 or 9 etc.

Challenge in vaccine development (can’t develop 94+ vaccines specific to each capsular type)

Hence, people take the most common capsular serotypes which are responsible for the most invasive disease, and create a vaccine that combines them

19
Q
A

Nasopharyngeal carriage of S. pneumoniae is necessary for transmission of bacteria and precedes invasive disease

The nasopharynx of young children is commonly colonised by potentially pathogenic bacteria including Streptococcus pneumoniae

Carriage is age dependent (more common in children)

19
Q
A

Nasopharyngeal carriage of S. pneumoniae is necessary for transmission of bacteria and precedes invasive disease

The nasopharynx of young children is commonly colonised by potentially pathogenic bacteria including Streptococcus pneumoniae

Carriage is age dependent (more common in children)

20
Q

What are conjugate vaccines

A

Polysaccharide vaccines (based on bacterial capsules) do not induce a strong or persistent immune response in young children

Polysaccharides become very immunogenic when linked to a carrier protein (e.g, tetanus toxoid) = conjugate vaccine

Importantly, conjugate vaccines induce memory responses and reduce nasopharyngeal carriage of bacteria, impacting on transmission
Plasma cell antibodies, memory B cells and all can be produced as a result of the Bcell - Tfh interaction

Conjugate vaccines against pneumococcus, Haemophilus influenzae type b (Hib), and serogroups C, A, W, and Y of meningococcus have contributed to the virtual elimination of bacterial meningitis caused by these bacteria and prevented more than a million deaths annually

Polysaccharides don't bind to the cleft in the MHC class II (only protein) 
hence polysaccharide vaccines only stimulate B cells (BCRs can bind to polysaccharides)

no real plasma memory cell response either as no costimulation via Tfh cells