STREP

Preventing Rheumatic fever

Rheumatic fever can be completely prevented by treating strep pharyngitis with penicillin. Treatment can be delayed for as much as a week and still effective. Rheumatic fever itself does not respond to penicillin.

Lancefield group

streptococcal strains are further subclassified into groups by the presence of different CELL WALL POLYSACCHARIDES Of all the groups (A through T), the most important strains in human disease are those of group A. The full taxonomic name of group A strep is Streptococus pyogenes.

What is a test for S. Pneumoniae?

EXPOSURE TO ANTIBODIES TARGETING CAPSULAR PROTEINS - Mixing with an antibody targeted towards capsular antigens - Causes capsule to swell which can be reviewed by phase contrast microscopy

Strep pneumoniae - Interaction with the blood brain barrier - What causes breaches in the blood brain barrier? - Why is there damage to endothelial cells (2) - Why are disruptions dangerous?

- After entering the blood stream, S. pneumoniae can gain access to cerebrospinal fluid and cause meningitis. - The blood-brain barrier normally excludes large molecules and particles. - S. pneumoniae is able to penetrate it and gain access to the brain through its ability interact with endothelial cells and elicit inflammatory reaction. INTERACTION W ENDOTHELIAL CELLS --> MEDIATION OF INFLAMMATION ---> DAMAGE TO ENDOTHELIAL CELLS ---> BLOOD BRAIN BARRIER COMPROMIZED The ENDOTHELIAL CELL are an important mediator of inflammation. - Damage to the endothelial cells appears to be due to the effects of IL-1 and TNFα elicited by action of bacterial cell wall components on the endothelial cells, - This leads to breaches in the vessel walls that lead to disruption of blood-brain barrier allowing for entry of bacteria and phagocytes into cerebrospinal fluid. - This is hazardous for the brain

Strep pneumoniae VIRULENCE FACTORS 3) PNEUMOLYSIN - Function

- Aids Strep pneumonia to bypass the clearance mechanisms of the upper airway to reach the lungs.

Strep pneumoniae VIRULENCE FACTORS 2) BACTERIAL ADHESIN - Function

- Binds to a N-acetylhexosamine-glycolipid on the cell surface

Streptococcus pneumoniae -Morphology & identification (3) - how many different serotypes are there?

1) MORPHOLOGY S. pneumoniae is a Gram-positive coccus and usually grows IN PAIR, so called "DIPLOCOCCUS". This morphological characteristic helps in identification of S. pneumoniae. 2) BILE SOLUBILITY • Bile solubility: Pneumococcus produces an enzyme called "AUTOLYSIN" that digests peptidoglycan. Bile (deoxycholic acid) activates the autolysin. Thus, S. pneumoniae strains lyse rapidly when suspended in a bile solution. 3) POLYSACCHARIDE CAPSULE & ANTIGENIC STRUCTURES - Thick polysaccharide capsule - CAPSULAR POLYSACCHARIDE IS IMMUNOLOGICALLY DISTINCT for each of the more than 90 serotypes

Treatments of streptrococcal infections (2)

1) PENICILIN Until recently, Streptococci remained generally sensitive to penicillin. Thus, penicillin has been the drug of choice for treating S. pyogenes and S. pneumoniae 2) ERYTHROMYCIN Erythromycin in penicillin allergy.

Diseases associated with Streptococcus pyogenes (5)

1) Strep throat (and Scarlet fever) 2) Scarlet fever 3) Streptoccocal toxic shock-like syndrome 4) Necrotizing fascitis 5) Delayed Sequelae - Rheumatic Fever

Strep pneumoniae VIRULENCE FACTORS 1) sLgA PROTEASE - Function

1) sLgA PROTEASE - Degrades proteins in the mucus to prevent it it from being traped & expulsion from the airway.

Virulence factors of S. Pneumoniae (3)

1) sLgA PROTEASE - Plays a role in colonization by helping the bacteria avoid trapping in mucus and expulsion from the airway. 2) BACTERIAL ADHESIN - Binds to a N-acetylhexosamine-glycolipid 3) PNEUMOLYSIN - Aids Strep pneumonia to bypass the clearance mechanisms of the upper airway to reach the lungs.

Strep pneumoniae - How does it induce an inflammatory response? - What is about its structure that incudes the response? - What inflammatory pathway do they activate? Classical?

A notable feature of S. pneumoniae is the ability of its cell wall constituents to provoke inflammation. 1) PEPTIDOGLYCAN FRAGMENTS 2) TEICHOIC ACID Symptoms of bacterial pneumonia such as fever and lung damage can be explained by the intense and unrestrained inflammatory response elicited by pneumococci growing in the lung. Peptidoglycan fragments and teichoic acid activate the ALTERNATIVE COMPLEMENT PATHWAY and elicit production of IL-1 and TNFα.

M Protein - Mechanism of action

ANTIPHAGOCYTIC FACTOR of STREP PYOGENS • M protein is the most important ANTIPHAGOCYTIC FACTOR of S. pyogens. This protein is required for virulence. Organisms lacking M protein are avirulent. M protein preferentially binds the SERUM BETA-GLOBULIN FACTOR H, which is a regulatory protein for the alternative complement pathway. Complement component C3b mediates opsonization, and factor H destablizes C3b. Thus the C3b that binds to the cell surface in the region of the M protein is degraded by factor H.

Strep pneumoniae - Survival in the lung

After reaching the lung, the bacteria encounter the next line of host defense, alveolar macrophages. Virulent pneumococci have an antiphagocytic capsule and are not engulfed by macrophages.

How does the TSS & TSLS toxins compare to one another in terms of mechanism of action and structure?

Although TSS and TSLS toxins have the same mechanism of action, they have little similarity in the amino acid sequence and structure. Instead, the TSLS toxin is most closely related to the toxin associated with scarlet fever.

Viridans Streptococcal Infection - What other bacteria contribute to the development of plaque? (3)

DENTAL CARIES Evidence suggests a central role of viridans streptococci in etiology of dental caries. Plaque formation on teeth is prerequisite for dental caries and periodontal disease. OTHER BACTERIA INVOLVED IN PLAQUE FORMATION (3) 1) S. mutans, 2) S. sanguis, 3) S. milleri These three colonize tooth surface and contribute to development of plaque.

Diseases associated with Streptococcus pyogenes 1) STREP THROAT/PHARYNGITIS - What percentage of sore throats are cause by S pyogenes? - What is the time frame for the symptoms to develop?

Group A strep (S. pyogenes) are the most common bacterial cause of acute pharyngitis (sore throat). About 20% of sore throat are caused by Group A Strep (the most of the rest cases by viruses). SYMPTOMS (2-4 days) PHARYNGITIS generally develops 2 to 4 days after exposure to the pathogen. It starts with an abrupt onset of soar throat, fever, malaise and headache. The posterior pharynx can appear erythematous with an exudate.

Streptococci - Biological Test? - how can they be classified?

Hemoylsis! Streptococci are a heterogenous group of bacteria They can be classified in three subgroups based on hemolysis test • α -- green zone around colonies; hemoglobins are reduced. • β -- clearing around colonies results from specific enzymes called hemolysins. • γ -- no zone of hemolysis, non-hemolytic. The main pathogens in this genus are the β-hemolytic strains.

Why is it someone can repeatedly be infected with strep throat?

M protein is found on Strep - It is highly immunogenic NUMEROUS SEROTYPES - There are 80 different M proteins that exist so can cause infection repeatedly due to nuermous serotypes

Diseases associated with Streptococcus pyogenes 4) Necrotizing fasciitis - What are the bacteria referred to as? - How are they introduced into the body? - Is this a serious disease? What the mortality rate?

Necrotizing fasciitis, a severe invasive Group A streptococcal infection, is characterized by an extensive destruction of muscle and fat that spreads along the fascial planes. - The organisms, referred to as flesh-eating bacteria, - Introduced into the tissue through a break in the skin. Mortality rate exceeds 50%, thus prompt and aggressive therapy is necessary to prevent them, including surgical debridement and even amputation.

Strep pneumoniae 1) Adherence & Colonization 2) Bypassing clearance mechanisms 3) Survival in Lung

S. pneumoniae is an exclusive human pathogen, which is spread from person to person by aerosols. 1) COLONIZATION he first step in the development of pneumonia is colonization of the nasopharynx by S. pneumoniae. (sLgA protease & bacterial adhesin assist in this step) 2) BYPASSING CLEARANCE MECHANISMS OF LUNG After colonization of the nasopharynx, S. pneumoniae must bypass the clearance mechanisms of the upper airway to reach the lungs. (pnemolysin assist in this step) 3) SURVIVAL IN LUNG - After reaching the lung, the bacteria encounter the next line of host defense, alveolar macrophages. - Virulent pneumococci have an antiphagocytic capsule and are not engulfed by macrophages. (antiphagocytic capsule prevents phagocytosis here)

Polysaccharide capsulde & Antigenic structure - Serotypes - Capsular polysaccharide -

S. pneumoniae strains have a thick polysaccharide capsule. The capsular polysaccharide is immunologically distinct for each of the more than 90 serotypes. But most cases of pneumococcal pneumonia are caused by a subset of 23 serotypes. Mixing a specimen containing S. pneumoniae with antibody to capsular antigens causes the capsule to swell which can be reviewed by phase contrast microscopy. This quelling test has been used as a quick test for identification of S. pneumoniae.

M protein -Structure

STRUCTURE • The M protein is a fibrillar molecule with its carboxy terminal rooted in the peptidoglycan of the cell wall and the amino-terminal regions extending toward the surface. The M protein is a MAJOR TYPE SPECIFIC PROTEIN. - CARBOXY TERMINUS = highly conserved, - - AMINO TERMINUS = ANTIGENIC DIVERSITY of the more than 80 M protein serotypes. • M protein is highly immunogenic and antibodies against M protein can protect host against infection. However, since more than 80 different M proteins exist, repeated strep infections with different serotypes are possible.

Diseases associated with Streptococcus pyogenes 5) Delayed Sequelae - Rheumatic fever - When does this come about? - What strains/serotype is this cause by? - What conditions does it cause? - Can they be resovled? - Which one(s) can't be resolved?

Strep throat, in most case, would resolve without treatment. However, it may be followed by rheumatic fever, which can be very serious disease. Rheumatic fever is caused by specific strains (M serotypes) of group A streptococci (e.g., M18 and M3). Strep throat is the only infection that may be followed by acute rheumatic fever. - Less than 3% of people with strep throat develop this sequel. - Rheumatic fever in most patients manifests polyarthritis, carditis or both. OTHER MANIFESTATIONS - Other manifestations include a neurological disorder, Sydennnham's chorea, subcutaneous nodules and erythema marginatum. IRESOLVABLE- CARDITIS All of these manifestations can resolve, except for CARDITIS. In severe cases, patients with rheumatic carditis die of heart failure. - More commonly, patients survive and recovered. But in some patients, cardiac damage progresses insidiously to severe valvular scarring. - Valvular scarring creates a new set of complications, some of which are directly caused by impaired heart functions, others by infection of damaged valves by bacteria that find their way into the bloodstream.

Classification of Streptococci - What is their growth pattern? - Gram Stain - Size/shape

Streptococci usually grow in chains - like strings of pearls. Gram Positive Cocci

Streptococcus pneumoniae - How common? - what infections does it normally cause? (2)

Streptococcus pneumoniae, also called pneumococcus, is one of the most common causes of bacterial pneumonia. DISEASES CAUSES 1) Infection of middle ear infection (otitis media) 2) Bacterial Meningitis

Diseases associated with Streptococcus pyogenes 3) Streptococal toxic shock Like Syndrome (TSLS) - Does this have superantigen activity?

The disease caused by S. pyogenes strains was called toxic shock-like syndrme (TSLS) because the clinical features are similar to those of staphylococcal toxic shock syndrome (TSS). NB: This strain causing TSLS differs from the other causing strep throat TSLS = SUPERANTIGEN - The toxin produced by the S. pyogenes strain responsible for TSLS is a superantigen, like TSS toxin produced by Staphylococcus aureus.

Streptoccocus pyogenes - What is it?/ organizationwise?

The full taxonomic name of group A strep (of the LANCEFIELD GROUP A-T) is Streptococus pyogenes.

What is the hypothesis behind why rheumatic fever develops?

The leading hypothesis is CELLULAR IMMUNITY. Streptococcal antigens evoke cross-reactive T cells. For example, various streptococcal preparations, including fragments of M protein containing heart cross-reactive epitopes, stimulate the production of cytotoxic T cells that react against cardiac myocytes.

Virulence Factors of group A streptococci - What is the best defined virulence factor of streptococci

The virulence of group A streptococci is determined by a variety of structure molecules, toxins and enzymes. Among them, M protein is the best-defined virulence factor.

Diseases associated with Streptococcus pyogenes 2) SCARLET FEVER - How does this manifest from Strep Throat? - When are symptoms observed - How are the symptoms different

This is a complication of STREPTOCOCCAL PHARYNGITIS and occurs when the infecting strain is LYSOGENIZED by a temperate BACTERIOPHAGE that stimulates production of a PYROGENIC EXOTOXIN SYMPTOMS (1-2 days after initial clinical symptoms of ST) - A diffuse ERYTHEMATOUS RASH appears on the upper chest and then spreads to the extremities. - Scarlet fever used to be a major killer of children, and has become rare since the advent of antibiotics.

Viridans (greening) streptococci - Where are these found? - What percentage of the bacterial flora do they make? - What is their level of virulence? - Why are these type of bacteria important in dentistry?

are reported simply as "non-β-hemolytic streptococcus spp". They comprise a number of species inhabiting the normal oropharynx, where they make up 30 -60% of normal bacterial flora. Although viridans streptococci in general are of low virulence, they include species, such as STREPTOCOCCUS MUTANTS responsible for dental caries.