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Microbiology (Streptococci (Beta haemolytic (complete) (Group C and G (S.…

- - - - 0.5-1.2um in diameter - oval or lancelate in shape
      - Catalase negative
      - Capsulated - large mucoid colonies, Non-capsulated are smaller and flat
      - Colonies autolyse with age
      - Alpha haemolytic (when grown aerobically)
      - Virulent strains - covered with complex polysaccharide capsule
        
        90 strains recognised by typing these polysaccharides
      - Purified antigens used a polyvalent vaccine
      - Virulence factors
        
        Capsule
        
        Forms basis of classification of serotypes
        
        Most than 90 strains identified, 20 serotypes account for majority of pneumococcal infections
        
        Anti-phagocytic and antigenic
        
        Provides protection from phagocytosis by preventing polymorphonuclear leucocytes from attacking. Allows bacteria to grown sufficiently before appearance of anticapsular antibodies
        
        Pili
        
        Enables attachment of encapsulated pneumococci to the epithelial cells of the upper respiratory tract
        
        Not all strains are piliated, but those that are tend to be more virulent
        
        Choline-binding protein A
        
        Major adhesin allowing pneumococcus to attach to carbohydrates on epithelial cells of the human nasopharynx
        
        Secretory IgA protease
        
        Inactivates IgA - first immunoglobulin bacteria needs to overcome
        
        Autolysins
        
        Enzymes that hydrolyse components of a biological cell in which it is produced.
        
        Lyt A,B and C - peptidoglycan hydrolysing enzymes that are present in the bacterial cell wall and are normally inactive
        
        Activated by surface active agents, beta-lactams or stationary phase --> release intracellular virulence factors (notably pneumolysin)
        
        Pneumolysin
        
        Usually retained within the cytosol of an intact pneumococci
        
        Cytotoxin (toxic to cells)
        
        Binds to cholesterol in the host membrane and creates pores to destroy ciliated epithelial cells
        
        Supressses oxidative burst
        
        Production of hydrogen peroxide - causes further tissue damage
      - Types of infections
        
        Exogenous
        
        Can also be transmitted from one infected individual by airborne droplets from a cough or sneeze
        
        Endogenous
        
        Bacteria colonises nasopharynx of carrier who develops resistance
        
        Individuals susceptible due to malnutrition, alcoholism, respiratory damage (following viral infection or depressed immune system)
      - Obligate parasite - cannot complete life cycle without exploiting its host
      - Cell wall contains choline - important for regulation of cell wall hydrolysis
        
        Must be present for activity of the autolysin amidase during cell division
        
        Some teichoic acid is exposed (substance C0 - precipitates C reactive protein in presence of calcium
      - Clinical significance
        
        MOPS
        
        Meningitis
        
        One of the most common causes of adult bacterial meningitis - This has a high mortality rate even when treated appropriately
        
        Otitis Media
        
        The most common bacterial infection of children - Most frequently caused by pneumococcus - characterised by earache
        
        Acute bacteria Pneumonia
        
        Usually cause by S. pneumonia and is the leading cause of death especially for the elderly and those whose resistance is impaired.
        
        Rapid onset
        
        May be coupled with a fever of 39-41oC because of activated immune response
        
        Mortality rate is usually higher with type 3 streptococcal pneumonia
        
        Frequently preceded by upper or middle respiratory viral infection, which predisposes (liable) to s. pneumonia infection of the pulmonary parenchyma
        
        Mechanisms include increased volume and viscosity of secretions that are more difficult to clear and secondary inhibition of the action of bronchial cilia by viral infection
        
        Sinusitis
        
        Bacteraemia/ Sepsis
        
        Most commonly caused by pneumococcus - especially in those who functionally or anatomically are asplenic.
        
        Bacteraemia occurs in 25-30% of pneumonia cases
        
        Bacteraemia occurs in up to 80% of meningitis cases
      - Treatment
        
        Most strains of pneumonia are still sensitive to penicillin and therefore if a patient is infected with s. pneumonia then this may be administered
        
        If patient is allergic to penicillin then erythromycin or tetracycline may be administered
      - Control/ Prevention
        
        Vaccines of capsular polysaccharides for 'at risk' patients
        
        Pneumovax - 23 serotypes
        
        Now included in childhood vaccination schedule
        
        Prevenar - 13 serotypes
  - - - S. pyogenes
        
        Usually form long chains when recovered from liquid culture but may appear as individual cocci, pairs or clusters of cells in gram stains of samples from infected tissues
        
        One of the most frequently encountered pathogens for humans worldwide so is clinically important
        
        Can infect intact skin or mucous membranes and progresses very rapidly
        
        A low inoculum suffices for infection
        
        Does not survive well in the environment - instead habitat is infected patients. Also found in normal human flora (less than s. aureus)
        
        Only known reservoir in nature is on skin and mucous membranes of human host
        
        Known to colonise oropharynx of children and young adults
        
        Infections caused by recently acquired strains spread by droplet infections and skin contact
        
        Epidemiology is transient and depends on the spread of production of antibodies to the particular m protein
        
        Clinical significance
        
        Major cause of cellulitis
        
        Can lead to necrotising fasciitis (NF)
        
        Acute pharyngitis or pharyngotonsilitis
        
        Most common type of s. pyogenes infection
        
        Also known as strep throat
        
        Associated with severe, purulent inflammation of the posterior oropharynx and tonsillar areas (will see a grey/ white exudate)
        
        Will usually show onset 2-4 days after exposure
        
        Patient may onset with fever, sore throat, headache, malaise and abdominal pain
        
        Complications from the release of pyrogenic exotoxins by the bacteria to which the patient does not have antibodies to may lead to scarlet fever.
        
        This is a complication released to group A strep throat. Scarlet fever may be suspected if a sunburn like rash develops on the neck, chest and may also spread across the body.
        
        Many strep throats are mild however those caused by viruses tend to more severe and therefore lab confirmation of streptococcal infection is vital for an accurate diagnosis and treatment programme. This is vital in the prevention of subsequent acute rheumatic fever and rheumatic heart disease
        
        Impetigo
        
        s. pyogenes is classic cause of this syndrome
        
        Disease begins on any exposed surface (most commonly legs)
        
        Typically occurs in children - causes severe and extensive lesions of face and limbs
        
        Treated with topical agent such as mupirocin or systemically with penicillin or by using first generation cephalosporins such as cephalexin which are effective against both s. aureus and s. pyogenes
        
        Comes under the category of pyoderma - any skin disease that is pyogenic (pus producing)
        
        Impetigo from GAS is non bullous
        
        When blisters rupture a honey coloured crust forms and when the crust dries a red mark is left which may fade and not leave a scar
        
        Serious impetigo infection can result in post streptococcal glomerulonephritis
        
        Can develop into necrotising fasciitis (NF)
        
        Erysipelas
        
        Puerperal sepsis
        
        Invasive group A streptococcal disease (Invasive GAS disease)
        
        Can develop into necrotising fasciitis (NF)
        
        Streptococcal toxic shock syndrome
        
        May occur following throat or soft tissue infection
        
        Treatment involves high dose of penicillin G plus clindamycin
        
        Predisposing factors: HIV, Cancer, diabetes, alcoholism and drug abuse
        
        Necrotising fasciitis
        
        Infection established in facial tissue below skin
        
        Infection of the subcutaneous fat layer, soft tissue and superficial fascia.
        
        Spreads rapidly causing tissue necrosis
        
        Follows entry of bacteria to skin or wounds or develops from cellulitis
        
        Can be fatal in a short period of time
        
        SpeA and B can be involved
        
        GAS enters the skin through a break and predisposing factors such as eczema, diabetes, insect bites and fungal infections can make individuals susceptible to impetigo
        
        Spread by close contact, sharing clothes and bedding
      - Cell wall
        
        Group A-specific C-substance
        
        Composed of Rhamnose and N-acetylglucosamine
        
        All group A streptococci by definition contain this antigen
      - Mainly spread by skin to skin contact or by respiratory droplets in crowded environments (e.g. playgrounds, classrooms etc.)
    - - S. agalactiae
        
        Grow as buttery appearing colonies on nutritionally enriched media
        
        Beta haemolysis only in a small zone
        
        Grouped into category by antigens on polysaccharide cell wall
        
        9 serotypes
        
        Produces several enzymes which allow for pathogenesis
        
        DNase
        
        Hyaluronidase
        
        Neuraminidase
        
        Proteases
        
        Hippurase
        
        Haemolysins
        
        Bacterium colonises GI tract then genitourinary tract
        
        Normal flora in vagina - not harmful until pregnancy
        
        Causes (Caused by all serotypes)
        
        Neonatal disease
        
        UTIs
        
        Wound infections
        
        Occasionally bacteraemia
        
        29.5% of reported neonatal bacterial meningitis
        
        mostly type 111
        
        <5% mortality rate, however 15-30% of cases have neurological sequelae
        
        Risk factors to infection
        
        Heavily colonised mother lacking specific antibody
        
        Premature rupture of membranes
        
        Pre term delivery
        
        Prolonged labour and obstetric complications (e.g. haemorrhage, ruptured uterus)
    - - S. equisimillis
      - S. anginosus
        
        Has polysaccharide antigens for group G
      - Less prevalent than infections by groups A and B
      - Sometimes cause pharyngitis and may also be associated with wound infections
      - Group G part of normal flora
      - Cases of bacteraemia reported for both group C and G infections
    - - E. faecalis
        
        E. faecalis causes more infections (responsible for 80-90% of human infections)
      - E. faecium
        
        E. faecium responsible for around 10-15% of human infections
      - 18 species of enterococci
        
        form part of normal flora of bowel
        
        facultatively anaerobic cocci
        
        grow optimally at around 35oC - however found at a range of temperatures (10-45oC)
        
        Grow as non-haemolytic colonies
        
        Halotolerant
        
        6.5% salt and 40% bile salts
      - Virulence factors
        
        Don't have many but can cause life threatening disease
        
        Aggregation substance (allows other cells to migrate to infection site)
        
        Carbohydrate adhesins (adhere to many different receptor types)
        
        Bacteriocin (breakdown other bacteria in area)
        
        Gelatinase (breakdown gelatine)
      - Treatment
        
        Resistant to many beta-lactams, aminoglycosides and vancomycin (Van A,B and C genes)
    - - Cause milleri infection
      - Grow in CO2 and form minute colonies on blood agar
      - Characteristic caramel odour
      - Normal flora of vaginal area
      - Involved in deep infections e.g. brain abscesses
    - - Composed of hyaluronic acid, identical to that found on human connective tissue
        
        This aids the cell in evading immune recognition
      - Anti-phagocytic
      - Present when bacteria is growing but is lost during the stationary phase
      - Some group A colonies may appear non-capsulated
    - - M protein (>80 types)
        
        Antiphagocytic - degrades C3b - binding to serum factor H (complement control protein)
        
        Opacity factor produced by 29 M types - opacifies serum (disrupts structure of HDLs resulting in the formation of large lipid vesicles that cause serum to become cloudy)
        
        M like proteins bind the Fc portion of IgG and IgA and alpha2macroglobulin a protease inhibitor
        
        Destroys C3 convertase preventing opsonisation by C3b
      - F protein
        
        Receptor for fibronectin (Fbp) - Attachment to fibronectin in the pharyngeal epithelium and skin
        
        Forms a bridge to a5-B1 integrins, which leads to rearrangement of cytoskeleton actin in host cells and uptake of invading s. pyogenes
      - Toxins
        
        Pyrogenic exotoxins
        
        (Spe) SpeA, SpeB and SpeC - Act as superantigens
        
        cause non-specific activation of T cells resulting in polyclonal t cell activation and massive cytokine release
        
        Cause various effects - including rashes seen in scarlet fever and streptococcal toxic shock syndrome
      - Streptolysins
        
        S
        
        Cell bound haemolysin
        
        Lyses erythrocytes, leucocytes and platelets
        
        Destroys phagocytes
        
        Oxygen stable
        
        Non-immunogenic
        
        Usually turned on when bacterium want to invade immune system. They are non-immunogenic due to their small size
        
        O
        
        Haemolysin activity - haemolysins are lipids and proteins that cause lysis of RBCs by destroying their cell membrane
        
        Inactivated by oxygen reversibly and irreversibly by cholesterol
        
        Stimulates antibody response
        
        Damage mammalian cells, resulting in lysis and release of lysosomal enzymes
      - Enzymes
        
        Streptokinases - A and B. Lyse blood clots
        
        Catalyses conversion of plasminogen to plasmin - causes lysis of fibrin clots which in turn facilitates the rapid spread of organisms
        
        Degradation of fibrin = fibrinolysis
        
        Streptodornases
        
        DNases that depolymerises cell free DNA in purulent material (pus producing material)
        
        DNases that degrade viscous DNA in necrotiszing tisssue or exudates (a mass of cells and fluid that has seeped out of blood vessels or an organ especially inflammation) aiding in the spread of infection
        
        C5a peptidase
        
        Produced by group A (s. pyogenes)
        
        Not required for s. pyogenes to prevent influx of neutrophils as bacteria spread through fascia (fascia is band or sheet of connective tissue, primarily collagen, beneath the skin that attaches, stabilises, encloses and separates muscle and other internal organs)
        
        potent neutrophil chemotaxis
        
        Hyaluronidase
        
        Act as a spreading factor
        
        Breaks down hyaluronic acid, an important component of connective tissue
        
        Diphosphopyridine nucleotidase
  - - - Autoimmune disease that occurs 2-5 weeks after initial infection
      - Associated with pharyngeal infection
      - Caused by cross reactions between antigens of the heart and joint tissues, and streptococcal antigen (especially M protein epitopes).
        
        Repeated attacks with different M types can lead to heart valve disease
      - Antibodies formed to cell wall antigen cross react with the sarcolemma of the heart - inflammation occurs of the heart valves, joins and blood vessels
      - Preventable if patient is treated within first 10 days following onset of acute pharyngitis
    - - Rare infection occurs as soon as 1 week after impetigo or pharyngitis occurs
      - Due to a few nephritogenic (agent causing nephritis) strains of group A streptococci
      - Ag-Ab complexes on the basement membrane of the glomerulus initiate the disease
      - No evidence that treatment of skin disease of phyaryngitis with penicillin with prevent condition
- - - - Both species are pyogenic
  - - - Capsule
      - Pili (Pil gene)
        
        Containing pilin protein
        
        Attachment to host epithelial and mucosal cell surfaces
        
        Aids in immune evasion - highly variable carboxy terminus (pili also antigenic)
      - Outer membrane proteins
        
        Por (pore forming)
        
        Gonococcus expresses single porin typee: PorB but other strains will express different ones
        
        Proteins not subject to high frequency phase or antigenic variation like other outer membrane antigens
        
        Opa (mediate binding to epithelial cells)
        
        Gonococcus can express up to 11 different Opa proteins - generally only a few expressed simultaneously
        
        Different Opa proteins bind to distinct receptors on host cells
      - Transferrin receptors
        
        Iron required for survival in vivo
        
        for iron acqusition and binding lactoferrin
      - Protease for cleaving IgA and Beta lactamase
    - - Attaches to mucosal cells in localised areas, urogenital, rectal or oropharyngea - colonisation
      - Enters cells and multiplies then passes through the cell into sub epithelial space
      - Contain LOS (lipooligosaccharide) which stimulates inflammatory response - release of TNF-alpha cause the symptoms
    - - Women 50% risk of becoming infected by single contact (men 20%)
      - Major reservoir is asymptomatically infected person
      - More common in women who often have mild or asymptomatic infection --> clear within a few weeks
    - - Men
        
        Urethra
        
        Purulent discharge and dysuria 2-5 days after infection
        
        95% have acute symptoms
        
        Complications (rare) - epididymitis, prostatitis and abcesses
      - Women
        
        Infection of columnar epithelial cells of endocervix
        
        Vaginal discharge, dysuria and abdominal pain
        
        Ascending infections cause --> salpingitis, abscesses and pelvic inflammatory disease (PID) in 10-20% of women
        
        Disseminated infection, septicaemia, bones and joint infection 1-3% women, and much less in men
    - - Perihepatis - Fitz-Hugh-Curtis syndrome
      - Purulent conjunctivis of the newborn - opthalmia neonatorum
      - Anal rectal gonorrhoea and pharyngitis (contracted by oral-genital contact)
    - - Diagnosis by growth on selective medium - gram stain and biochemical tests (e.g. gonochek and Api strips)
        
        Grows best under aerobic conditions and most strains require enhanced CO2. Utilises glucose as a carbon and energy source - not maltose, lactose or sucrose.
      - All members of Neisseria genus are oxidative positive and so the oxidative test can be used to identify neisseria but cannot be used to distinguish between gonococci and meningococci
      - Thayer-martin medium (chocolate agar supplemented with several antibiotics that suppress growth of non-pathogenic neisseria and other normal and abnormal flora) is typically used to isolate gonococci.
        
        This medium is important for cultures that are typically obtained from sites such as the genitourinary tract or rectum, where there is a normal abundance of flora. (On nonselective media, the normal flora overgrows the gonococci.)
    - - Resistant to penicillin, tetracycline, cefoitin and/or spectinomycin.
      - Third generation cephalosporins effective against organism
  - - - Capsule
        
        Polysaccharide capsule is antiphagocytic and therefore most important virulence factor
        
        Antigenically diverse which allows the identification of at least 13 capsular polysaccharide types - called serogroups
        
        Types A,B and C most commonly associated with meningitis
      - Outer membrane proteins
        
        Used for serological classification (serotyping)
        
        Group A - single serotype Group B and C - multiple serotypes
    - - Worldwide occurance
      - 90% of cases caused by A,B and C
        
        Vaccine available for groups A and C
        
        Capsule of type B contains neuramic acid which is found in human nervous system (not immunogenic)
      - Transmitted by respiratory droplets during close contact
      - Humans only natural carriers
        
        Carriage rate varies by <1-40%
        
        Carriage may be transient, intermittent or chronic
        
        Carriage results in serogroup specific antibodies which are cross reactive
      - Disease may result from the individuals carriage strain or a new strain to which they lack antibodies
      - Outcome of exposure depends on: colonisation of the oropharynx, presence of preformed antibodies, systemic spread without phagocytosis, whether toxic effects of LOS endotoxin are expressed and access to CNS
    - - Antiphagocytic properties of the meningococcal capsule aid in the maintenance of infections
      - LOS, release during autolysis and in outer membrane vesicles, is responsible for the toxic effects found in disseminated meningococcal disease.
      - Meningococci, like gonococci makes an IgA protease that cleaves IgA and thus helps the pathogens to evade immunoglobulin of this subclass
    - - Meningitis
        
        Abrupt symptoms headache, fever, photophobia. May be non-specific vomiting or fever
      - Meningococcemia with or without meningitis
        
        Thrombosis of small blood vessels and multiorgan involvement
        
        DIC with shock and adrenla gland destruction
        
        Waterhouse-Friderischsen syndrome
      - May also cause milder chronic septicaemia with fever, arthritis and skin lesions
      - Pneumonia, arthritis and urethritis
      - Important to treat as soon as symptoms recognised
        
        Prophylaxis for contacts
      - CSF
        
        Blood cultures
        
        Gram stain
        
        Biochemical test
        
        PCR
      - Bacteria meningitis CSF
        
        Increased pressure, elevated protein, decreased glucose and many neutrophils. The presence of an infecting organism or of antigenic capsular substance confirms the diagnosis
    - - Grows on chocolate agar. Oxidase positive
  - - - NG - glucose +, maltose - , lactose -
      - NM glucose +, maltose + , lactose -
      - NL glucose +, maltose + , lactose +