• Anaerobes : Facultative
• Limited metabolism
• Catalase negative
• 29 species

Streptococcus

Lancefield typing scheme

Detect specific sugar with antisera 

Group A: rhamnose-N-acetylglucosamine (Streptococcus pyrogenes)

Group B: rhamnose-glucosamine (Streptococus agalactiae)

Group A, B, C, F, and G (Streptococcus anginosus)

Not classified:  Streptococcus pneumoniae)

Streptococcus pyrogenes

Habitat and Transmission

Habitat:  Human pharynx, skin, musocal surfaces

Transmission: droplets or direct contact

• Antigenic variation of the M Protein
• More than 150 antigenic types: M1, M2, etc
• Antisera to various M types
• Determine emm sequence
• Certain M types associated with specific outcomes of infection
• Class I: pharyngeal & invasive
• Class II: skin, non-specific

• M Protein
• Polysaccharide Capsule
• Bunch of Exoproteins!
• Amylase
• Streptolysin O, S
• SPE B (Cysteine protease)
• Glucuronidase
• SPE A, C
• Mitogenic factor (DNase B)
• DNase A, C, D
• Bactericins
• Phosphatase
• Streptokinase
• Serum inhibitor of complement
• Leucyl aminopeptidase
• NADase (ADP=ribosylase)
• Autolysins
• Enterotoxins

GAS Virulence Factor: M protein

• alpha-helical, coiled-coiled
• Antiphagocytic (binds human proteins)
• Factor H, C4b - inhibit complement activation
• IgA-Fc
• others

• Inhibits phagocytosis
• Composed of hyaluronic acid
• Identical to that found in  human tissue (molecular mimcry).  Not antigenic

• Asymptomatic: .5-4%
• Pharyngitis or "Strep throat" 5/1000
• Impetio
• Erysipelas
• Scarlet Fever (Strawberry tongue)
• Toxic shock syndrome - 3,000 cases in US/year
• Necrotizing fascilitis

• Pharyngitis
• Scarlet Fever
• Toxic Shock syndrome
• Skin Diseases

• Acute rhematic fever (Heart disease/Arthritis/OCDs)
• Acute glomerulonephritis

• Post infection sequelae (pus)
• Immune complex -> inflammation
• Glomerulonephritis

• Sydenham chorea
• Post-infection sequelae
• Tourette's syndrome , tics, obsessions (OCD)
• Immune sequelae of GAS aby's attach basal ganglia

• Impetigo
• Scarlet Fever
• Erysielas
• Pharyngitis
• PANDAS
• Rheumatic fever
• Glomerulonephritis
• Toxic shock syndrome
• Necrotizing fasicilitis

• 12 complete genome sequences of GAS
• >85% genome sequence is conserved among 12 strains (core genome)
• Pan Genome - 2,500 genes
• Elements of the pan genome likely to contribute to variability in the outsomes of infection

1. Prophage
2. Integrated conjugative elements (ICE)

1. Staphyococci
2. Enterococci
3. Clostridia
4. Streptococci

THE GENOME IS PLASTIC

GAS

What caues change in expression?

• Stability of transcriptome (difference during in vitro culture) suggests a stable genetic change

GAS

Invasive transcriptome associated with covS mutation

• All pharyngeal profile colonies/isolates: covS+
• All invasive colonies/isolates: covS-
• PERFECT correlation between covS allele and invasive transcriptome profile

GAS

Why do invasive variants acquire mutations in covS?

• Trigger for invasive disease (covS- -> No SpeB (degrades SKA))
• In the absenc of SpeB, human plasmin accumulates on bacterial surface, which contributes to the invasive phenotype

Neutrophils critical in limiting infection

1. Ways to kill baceria
2. Phagocytosis
3. Antimicrobial peptides
4. Reactive oxygen etc.

GAS

NET

• DNase A,B,C,D
• SdaB = Mitogenic Factor/SpeF:  only chromosomally encoded DNase
• Streotidirnase 1 (Sda1) encoded by a prophage associated with current episodes of invasive infection

• Sda1 degrades NETS -> Contributes to viability of organism
• SpeB -> degrades Sda1
• Acquisition of Sda1-containing prophage puts selective pressure (via neutrophil survival) on the accumulation of covRS mutations to abrogate speB expression
• The mutations are associated with an invasive phenotype and hence the increase in invasive disease episodes since the global disseminatin of M1 clones

1. Entry SpeB
2. Mutation in CovRS
3. DNA NET destruction
4. Invasion

GAS

Control

• B-lactams:  100% susceptible, 35% clinical failure rate
• Intracellular reservoir
• B-lactamse producing normal flora

• M protein
• C5a peptidase
• SpeB

Catalase + Staphylococci (grows in clusters)

- Streptococci (grows in chains)

• beta-hemolytic- Groups A, B, C, F, and G (typed using Lancefield grouping system)
• alpha-hemolytic - Streptcoccus Viridans group an dStreptococcus pneumoniae
• gamma-hemolytic - Group D Streptococci and Enterococci

• Group A (Streptococcus pyrogenes): Rhamnose-N-acetylglucosamine polysaccharide
• Group B (Streptococcus agalactiae):  Rhamnose-glucosamine polysaccharide

Group B streptococci

S. agalactiae

• Major cause of disease in neonatal and perinatal periods
• Early onset (Ascending infecion in utero, ruptured fetal memmbranes, passage through colonized birth canal)
• Late onset (Nosocomial infection)

Group C and G Streptococci

S. dysgalactiae

• Groups C and G associated with pharyngitis, but generally not sequellae seen with Group A streptococci
• Compromised hosts - Deep abscesses, bacteremia

• Large group of alpha-hemoltic streptococci- part of the normal flora of the upper respiratory tract
• 30-40% of all cases of aubacute bacterial endocarditis - Associated with dental procedure
• Penicillin resistance

• Community acquired pneumoniae (CAP)
• Adult menigitis
• Sinusitis, otitis media
• Bacterimia

• Optichin susceptible = Streptococcus pneumoniae
• Optichin resistant = Other alpha-hemolytic Streptococci

• Two types - Opaque and transparent (transparent (no capsule) binds nasopharyngeal region))
• Immunity is due to specific anti-capsular antiboides
• Infection develops as a result of aspiration of nasopharyngeal secretions (Extremes of age, smokers, COPD, Decrease in ciliary activity)

Pathogeness of penumococcal pneumonia

• Capsule is anti-phagocytic
• Inflammation in lung is due to cell wall components: teichoic acid and phosphorylcholine
• Extensive tissue damage causes fluid accumulation and PMN recruitment
• Pneumococci use the fluid as a growth medium and serves to move the organism to other areas of lung and beyond

• Red hepatization - endothelium is damaged and RBC's are lost in tissue
• Grey's hepatization - Extensive PMN recruitment and fibrin deposits - antibody is produced (beginning of recovery)
• Organism can escape and seed the blood and meninges

S. Pneumonia

Virulence Factors

• Polysaccaride capsule (Over 80 different types, anti-capsular antibody is protective)
• PspA-Cell wall protein-protection against host complement
• Hyaluronidase - Degrades extracellula matrix - Important in pneumococcal pneumonia
• Pneumolysin-cytotoxic to ciliated bronchial epithelial cells - slows cilary beating.  Cytoplasmic enxyme - works in concert with LytA autolysin
• Pneumococcal surface antigen - Mn and Zn transporter
• Neurominidase - Important in otitis media pathogenesis - cleaves mucin found in eustachian tube

S. Pneumonia

Naturally competent

• Naturally competent for a small period of time early in exponential growth