Transcript Chapter 10: Gram

Chapter 10: Gram-Positive Rods
1.
Corynebacterium (Coryneforms)
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Genus: Corynebacterium
Species: Corynebacterium diphtheriae
Corynebacterium xerosis
Corynebacterium pseudodipheriticum
Corynebacterium ulcerans
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General Genus Characteristics
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Gram (+) straight or slightly curved bacilli, frequently swollen one or both
ends (club-shaped)
Methylene Blue film metachromatic granules – polyphosphate storage
granules (velutin)
VERY resistant to drying
Non-spore former
Binary fission (cell division) – characteristic V and L shaped figures;
“Chinese Letters”
Non-motile and unencapsulated
Most spp. are facultative anaerobes
C.diphtheria Gram stain
Methylene blue stain from
Loefflers slant
Arrangement of C. diphtheria
‫كرينه باكتريوم‬
‫محيطهاي كشت ‪:‬‬
‫تلوريت پتاسيم‬
‫لفلر‬
‫تينسدال‬
‫‪CTA‬محيط پاي ٌه قندي‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫كرينه باكتريوم‬
‫بيوتايپهاي كرينه باكتريوم ديفتريه در محيط تلوريت پتاسيم •‬
‫از هم جدا مي شوند ‪:‬‬
‫بيوتايپ گراويس به شكل گل مينا و بزرگ •‬
‫بيوتايپ مي تيس به اشكال مختلف(تخم مرغ نيمرو)و •‬
‫متوسط‬
‫بيوتايپ اينتر مديوس كوچكتر از بقيه و به شكل تخم •‬
‫قورباغه‬
Gram-Positive Rods
1. Corynebacterium (Coryneforms)
– Growth Conditions
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Selective Media – blood tellurite
reduction of tellurite
gray/black colonies
3 biotypes of C. diphtheriae
– Gravis: grave infection
– Intermidius: intermediate infection
– Mitis: little infection
***All 3 serotypes are capable of producing the same
toxin & clinical disease.
Gram-Positive Rods
1. Corynebacterium (Coryneforms)
• Corynebacterium diphtheriae
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Normal Flora – URT (throat and Nasopharynx)
Reservoir – Human pathogen ONLY
Infection
1. Respiratory (diphtheria)
2. Cutaneous (skin infection)
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Transmission/Epidemiology – person-to-person
(asymptomatic or diseased patients)
1. Inhalation of aerosols (i.e., respiratory droplets)
2. Direct contact w/ cutaneous lesions (analogous to impetigo)
3. Direct contact w/ contaminated fomites=‫( لوازم اشياء‬least
frequent)
Gram-Positive Rods
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Corynebacterium (Corniforms)
Corynebacterium diphtheriae
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Virulence Factor
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Diphtheria Toxin – very powerful exotoxin
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Avirulent C. diphtheriae  infected by bacteriophage (tox +) 
Lysogenic conversion to Virulent stain C. diphtheriae (tox +)
Recall: Lysogeny – bacteriophage has ability to insert their DNA into DNA
molecule of host bacterium.
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Expression of tox gene
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Regulated by Fe concentration
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Tox gene repressor: Fe-containing protein
Function of repressor – inhibits toxin production
[Fe2+] decreased  limited repressor available  toxin gene
Gram-Positive Rods
1. Corynebacterium (Corniforms)
• Corynebacterium diphtheriae
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Pathogensis
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Diphtheria Toxin – 2 subunit fragments A & B
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B Fragment: Binds to specific cell surface receptors
Mediates transport of A fragment into cell
A Fragment: Inhibits protein synthesis => cell death/necrosis
» Specifically, fragment A catalyzes a rxn. between NAD+
and the polypeptide chain elongation factor, EF-2:
transfer of ADPR from NAD+ to EF-2
» Result = ADPR:EF-2 complex is INACTIVATED &
protein (peptide) synthesis is terminated
Gram-Positive Rods
1. Corynebacterium (Corniforms)
• Corynebacterium diphtheriae
– Clinical Disease
1. Localized infection
 Respiratory (Pharyngeal Diphtheria)
 Cutaneous Diphtheria (both toxigenic & non-toxigenic
strains)
2. Systemic infection - toxemia
Gram-Positive Rods
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Corynebacterium (Corniforms)
Corynebacterium diphtheriae
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Pharyngeal Diphtheria
Mode of Infection
1. Inhalation
2. Attachment – to mucous membranes of passageways of oral cavity
3. Attachment/Colonization – non-specific virulence factors
4. Toxin production – necrosis of mucosal cells  lesion expansion= ‫توسعه بسط انبساط‬
5. Pseudomembrane formation – grayish-white patches= ‫ تكه وصله مشمع روي زخم‬of thick
fibrous exudate (neutrophils, corynebacterium, epthelial cells)
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Tight=‫ سفت محكم مانع دخول هوا‬adherence – to epithelial surface w/ no invasion of
underlying tissue
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Spread of pseudomembrane – involvement of nasopharyngeal tissues (mouth,
pharynx) or larynx & trachea
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Entry of toxin into the blood stream – multi-organ involvement: heart, CNS and
kidneys; most frequent & serious damage d/t toxin occurs in the heart and CNS, w/ death resulting
from damage to the heart.
Gram-Positive Rods
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Corynebacterium (Corineforms)
Corynebacterium diphtheriae
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Pharyngeal Diphtheria: Summary
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Location infection of the throat (URT infection)
Production of thick, grayish, adherent exudate
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Pseudomembrane
 Composition = cell debris from mucosa & inflammatory products
 Coats the throat; may extend into nasal passages or downward
into RT, obstructing the airways leading to suffocation
w/ disease progression – generalized sx’s d/t production &
absorption of toxin
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MAJOR CLINICAL EFFECTS: Heart & Peripheral Nerve involvement
 Cardiac conduction defects & myocarditis  CHF & permanent
heart damage.
 Neuritis of CN’s & paralysis of muscle grps – seen in late dis.
Gram-Positive Rods
1. Corynebacterium (Corineforms)
• Corynebacterium diphtheriae
– Cutaneous Diphtheria
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Localized infections arising from: insect bites,
skin trauma, poor personal hygiene
 Ex. Puncture wound or cut in skin  introduction of
bacterium into subcutaneous tissue  chronic, nonhealing ulcer w/ grayish membrane.
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Risk Group: homeless
Sx’s: impetigo-like lesions
Gram-Positive Rods
1. Corynebacterium (Corineforms)
• Corynebacterium diphtheriae
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Systemic Spread of Primary Infection
1. Heart – myocarditis
2. CNS – cranial & peripheral; nerve degeneration (paralysis)
3. Kidneys – filtering inadequacies; kidney failure
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Risk Groups
Individuals w/ low socioeconomic status
Crowded & unsanitary conditions
Non-immunized children (1-10 yoa)
Elderly – low immunization status
Gram-Positive Rods
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Corynebacterium (Corineforms)
Corynebacterium diphtheriae
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Diagnosis
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Clinical: sx presentation (gray-membrane w/ swelling)
Serological: Ab detection (to the toxin Ag.)
Laboratory identification
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Specimen – swab cultures ( pharynx, nasopharynx, or cutaneous
sites)
Microscopic appearance – smears alone are unreliable, possible
presence of diphtheriods
Cultivation – Media
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Loeffler media
Overnight growth  film (Methylene Blue)  metachromatic granules
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Selective media (Tinsdale agar, containing tellurite)
Blood tellurite  corynebacterium reduce tellurite  gray/black colored colonies w/ halos
Tinsdale’s Agar contains Potassium tellurite, an inhibitor of other respiratory flora
Gram-Positive Rods
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Corynebacterium (Corniforms)
Corynebacterium diphtheriae
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Treatment:
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Respiratory Diphtheria
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Cutaneous Diphtheria
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Passive Immunization: DAT (Diphtheria antitoxin) => for
neutralization of the toxin
Antibiotic Tx: penicillin or erythromycin => slows infection spread by
killing the organism, preventing further toxin production
Compresses soaked in penicillin applied to lesions
Control/Prevention
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Active Immunization – toxoid vaccine (DPT)
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Start @ infancy; booster injections – administered @ ~10yr. Intervals
throughout life
Harvest bacteria  purify toxin  inactive toxin  Formaldehyde
 toxoid
Gram-Positive Rods
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Corynebacterium (Corineforms)
Diphtheroids
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Other corynebacterium spp. that morphologically resemble C.
diphtheriae
Non-pathogenic
Normal flora – eyes (conjunctiva), skin, nose, mouth/throat,
vagina and urethra (UT)
NO toxin production
Opportunistic infections, esp. in immunosuppressed pts.
Ex. 1. Corynebacterium xerosis – opportunist in eye & postoperative infections
2. Corynebacterium pseudodipheriticum – endocarditis
in pts. undergoing cardiac surgery/valvular prostheses
Gram-Positive Rods
2. Bacillus
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Genus: Bacillus
Species: Bacillus anthracis – causes anthrax
Bacillus cereus – GI infection
Microscopic Morphological Appearance
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Large, Gram (+) bacillus
***Spore former*** (Endospores)
Non-motile
Encapsulated
Aerobe (strict or facultative)
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Note: most species of Bacillus are found in soil & water, and
are usually encounters in the medical laboratory as airborne
contaminants
Most clinically important = B. anthracis (Anthrax)
Gram-Positive Rods
2. Bacillus
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Virulence factors
1. Capsule
2. Exotoxin – complex of 3 protein factors
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Edema Factor (EF)
Protective Agent (PA)
Lethal Factor (LF) => EF + host cell calmodulin
Action of Exotoxin
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PA inserts into the cytoplasmic (phospholipid) membrane of
host  EF binds to PA  transfer of EF into host
cytoplasm
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PA facilitates transfer of EF into host cytoplasm
Gram-Positive Rods
2. Bacillus
– Action of Exotoxin (Pathogenesis)
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Rxn: EF + calmodulin → → activation of Adenyl
Cyclase [ ATP → cAMP] → ↑cAMP => EDEMA
– Increased levels of cAMP → cell oversecretion
(EDEMA)
– Transmission – animal to man
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Cutaneous infection
Pulmonary infection
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Intestinal infection
3 diff. types of infection
-based upon route of entry
Gram-Positive Rods
2. Bacillus
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Human Anthrax
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Causative agent = B. anthacis; rare in US
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1984-1997: only 3 cases of cutaneous anthrax reported
2001: 20 cases – probable exposure to B. anthracis powder
sent thru US mail; unknown source.
Epidemiology
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Anthrax is an enzootic disease of worldwide occurrence.
Enzootic diseases are endemic to an animal population;
occurrence changes little over time.
Anthrax affects domestic herbivores
» Sheep, goats, horses
Transmission to humans by contact w/ infected an. products
or contaminated dust (fig 10.6 p. 95)
Gram-Positive Rods
2. Bacillus
– Human Anthrax
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Epidemiology
– Infection initiated by subcutaneous innoculation of
spores thru incidental skin abrasions
– Also, but less frequently, inhalation of spore-laden dust
causes Pulmonary Anthrax
– Spores can remain viable for many years in
contaminated pastures, bones, wool, hair, hides, or
other an. materials.
» Highly resistant to physical & chemical agents
Gram-Positive Rods
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Bacillus
3 different types of B. anthracis infection
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Cutaneous Anthrax – m/c; localized infection of skin; Least dangerous
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Inoculation of spores → deposit beneath the skin, where they germinate
→ resulting in exotoxin production
Malignant pustule – located on hands, forearms and head
Eschar – black scab (painless)
Possible invasion to regional lymph nodes, then entry into general
circulation
Pulmonary Anthrax = Woolsorter’s Disease
– Most serious, but least common in US; mortality rate ~100%
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Inhalation of spores → deposit in lung alveoli
Characterized by progressive hemorrhagic lymphadenitis
Occupational risk groups; transmission of spore to individuals working w/
infected animals
Sx’s: onset – sudden w/ high fever & respiratory distress (similar to
respiratory infection.
Pneumonia is often followed by sepsis and death in untx’ed cases
Gram-Positive Rods
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Bacillus
3 different types of B. anthracis infection
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Gastrointestinal Anthrax
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Ingestion of spores → exotoxin production in intestinal tract → necrotic
lesions
Results from eating contaminated meat
Immunity = permanent immunity is acquired post infection
Treatment: broad spectrum antibiotics; penicillin is NOT
recommended b/c of inducible β-lactamase in B. anthracis
Control/Prevention
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Sterilization of wool, hair, etc. prior to the handling of animals
Sacrifice of infected animals
Immunization of animals
Vaccine for workers in high risk occupations – purified toxoid
Post-exposure antibiotic prophylaxis
Gram-Positive Rods
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Bacillus
Bacillus cereus
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Common inhabitant of rice when spores NOT killed properly
Infection/Disease
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Virulence factor
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Enterotoxins
Sx’s
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Gastroenteritis – Food intoxication: eating cooked, improperly
stored rice
Emetic-type gastroenteritis
Gastroenteritis – abdominal pain, diarrhea
Emetic-type gastroenteritis: vomiting
Control/prevention
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Refrigeration of food – no germination of spores
Gram-Positive Rods
3. Listeria
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Spp. are short, slender, Gram (+) rods
Non-spore formers
Occur in short chains or diplobacilli
Intracellular parasites
Catalase (+)
“tumbling” motility, as seen by light microscopy in
liquid medium @ 25°C
Distinct from catalase (-) streptococcus & nonmotile corynebacterium
Grow facultatively
Gram-Positive Rods
3. Listeria
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Epidemiology
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Listeria monocytogenes = ONLY spp that infects humans
Listeria spp are widespread in nature among animals
Human infections are usually food-borne
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2-3% processed dairy products (ice cream, cheese)
20-30% ground meats
Majority of retail poultry
Refrigeration does NOT suppress growth in food
1-15% of healthy humans are asymptomatic intestinal carriers
Infections are m/c in pregnant females, fetuses/newborns,
immunocompromised individuals (i.e., elderly, corticosteroid use)
 200 cases reported/yr. in US w/ 450 deaths & 100 stillbirths
Gram-Positive Rods
3. Listeria
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Pathogenesis of L. monocytogenes (fig 10.8 p.98)
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Attaches to & enters a variety of mammalian cells by
normal phagocytosis (i.e., macrophages)
Escape from phagocytic vacuole d/t formation of
Listeriolysin O, a membrane-damaging toxin.
Growth in host cell cytoplasm, stimulating changes in cell
function that facilitate its direct passage from cell-to-cell
 Assembly of actin filament tail that pushes the bacterium to
the surface of the macrophage
 Pseudopod extension forms, facilitating transfer into another
phagocyte.
 Membrane-degrading phospholipases mediate passage
of org into next cell w/ IS avoidance
Gram-Positive Rods
3. Listeria
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L. monocytogenes Clinical Disease (Listeriosis)
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M/C = septicemia & meningitis
Focal skin lesions (granulomatous) sometimes seen
Immunocompromised individuals w/ defects in cellular
immunity – potential serious infections
Pregnant females in 3rd trimester may have mild “flu-like”
illness
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This and asymptomatic colonization of vaginal tract – can
allow organism to be transmitted to newborn
» L. monocytogenes = common cause of newborn
meningitis
Gram-Positive Rods
3. Listeria
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Laboratory Dx of L. monocytogenes
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Isolation of organism from Blood, CSF
Blood agar – production of small colony, surrounded by
narrow zone of β-hemolysis
Distinguishable from streptococci
 + motility
 Production of catalase
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Treatment: antibiotic therapy
Prevention: proper food preparation & handling
Gram-Positive Rods
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Miscellaneous Non-spore forming, G(+) Rods
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Propionibacterium
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Lactobacillus
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Common inhabitants of normal skin
Genus of anaerobic or microaerophilic rods of diphtheroid-like morphology
Rare cases of endocarditis
P. acnes = strict anaerobe; causes acne
Commensal flora of human mucous membranes
Produce lactic acid during fermentation
Assist in maintaining acid pH of normal mucous epithelia
Acid production by oral lactobacilli => dental caries
Erysipelothrix rhusiopathiae
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Filamentous, Gram (+) rod that causes dis. in animals
Rare skin infection in humans who handle animal products (i.e., butchers,
DVM’s, fisherman(
Chapter 11: Neisseriae
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Genus Neisseriae consists of Gram-negative,
aerobic cocci.
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Organisms primarily reside on mucosal surfaces
2 Neisseriae spp are pathogenic for humans
1. N. gonorrhoeae (gonococcus)
 Cuasative agent for gonorrhea
2. N. meningitidis (meningococcus)
 Frequent cause of meningitis
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Gonocci & Meningococci
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Both are non-motile DIPLOCOCCI; look very similar
Both are pyogenic cocci b/c infections are characterized by
production of purulent material comprised largely of WBC’s
Neisseriae
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General characteristic of the Genus
1.
Gram-negative Diplococci (kidney-bean shaped)
Small, round, glistening, white-to-cream colored after 24 hr. colonization
Non-hemolytic
Non-motile
Non-spore forming
Oxidase-positive (presence of enz. cytochrome oxidase – for rapid dx)
Fastidious growth requirements
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Optimal growth temp = 37°C
Aerobic or microaerophilic, utilizing an oxidative form of metabolism
Require atmosphere of 5% CO2
Require thiamine and thiamine pyrophosphate for nucleic acid biosynthesis
Produces catalases, using the enzymes for fermentation of certain CHO’s
Highly Autolytic – autolysis causes cell wall breakdown (PG fragments) –
highly inflammatory
Highly sensitive to dessication d/t capsular polysaccharide
Laboratory tests for distinguishing pathogenic strains from commensal strains
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N. gonorrhoeae => (+) for glucose utilization, (-) for maltose utilization
N. meningitidis => (+) for glucose utilization, (+) for maltose utilization
Neisseriae
• NEISSERIAE GONORRHOEAE
– One of m/freq’ly reported infectious diseases in US
– Causative agent = N. gonorrhoeae, a Gram (-)
Diplococcus
– Commonly found w/in PMN leukocytes of clinical
samples
– Transmitted via sexual contact; rarely during delivery
thru infected vaginal canal
– Survival rate outside body = LOW d/t high sensitivity
to drying
– Epidemiology: major health problem worldwide
Neisseriae
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NEISSERIAE GONORRHOEAE
– Structure of Gonococci: Unencapsulated,
piliated, non-motile, diplococci
1. Pili – hairlike surf. Appendages;
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VIRULENCE Factor!
Composed of protein pillin
Enhance attachment to host epithelial & mucosal cell
sufaces
Confers resistance to phagocytosis
Potential to produce genetically different pilin molecules
over time – antigenic variation or gene conversion
Neisseriae
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NEISSERIAE GONORRHOEAE
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Structure of Gonococci: Unencapsulated, piliated,
non-motile, diplococci
2. Lipoligosaccharide (LOS)
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w/ shorter, more highly branched, non-repeat O-antigenic side
chains that do the LPS’s of other Gram-negative bacteria
Human serum IgM Ab’s are directed toward LOS Ag’s
3. Other Membrane Proteins (OMPs)
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Contribute to the virulence of N. gonorrhoeae
OMP II = “opacity protein” b/c its presence renders
gonococcal colonies less translucent; along w/ pili – mediated
attachment of organism to host cell.
Neisseriae
• NEISSERIAE GONORRHOEAE
– Pathogenesis
• Pili & OMP II => facilitate adhesion to epithelial
cells of urethra, rectum, cervix, pharynx,
conjunctiva
– Make colonization possible
• Production of IgA protease that cleaves human
IgA Ab’s – evasion of IS response
– Seen w/ BOTH gonococci & meningococci
Neisseriae
• NEISSERIAE GONORRHOEAE
– Clinical Notes
• 4th m/c Sexually Transmitted organism today
• Colonization of mucous membrane of GU tract of
rectum
• Cause localized infection w/ production of pus
• May lead to tissue invasion, chronic inflammation
& fibrosis
• Females > males w/ regard to being asymptomatic
carriers – can transmit gonococcal infection
Neisseriae
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NEISSERIAE GONORRHOEAE
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Clinical Diseases
1. Genitourinary Tract infections
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Acute & easy to Dx in Males
 Pt. presents w/ yellow, purulent urethral discharge &
painful urination.
Female – infection w/in endocervix (cervicitis) & extends to
urethra & vagina
 m/c presentation = greenish-yellow discharge;
intermenstrual bleeding is possible
 May progress to uterus, causing Salpingitis (inflammation
of Uterine/Fallopian Tubes), Pelvic Inflammatory Disease
(PID): gonococci ascend to Reprod. Tract – affect uterus,
ovaries & contiguous structures; destruction of upper
reproductive tract mucosa
 20% infertility rate w/ gonoccocal salpingitis d/t tubal
scarring
Neisseriae
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NEISSERIAE GONORRHOEAE
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Clinical Diseases
2. Rectal Infections (Proctitis) – seen w/ male homosexuals
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Sx’s: constipation, painful defecation, purulent discharge
3. Pharyngitis
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Contracted by oral-genital contact
Sx’s: purulent exudate; may mimic mild viral or streptococcal
sore throat
4. Opthalmia Neonatoreum
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Infection of the conjunctival sac acquired by newborn during
passage thru infected birth canal
Blindness if untreated
Tx: 1% Silver Nitrate on eyes prevents disease or 1%
Tetracycline or 0.5% erythromycin
Neisseriae
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NEISSERIAE GONORRHOEAE
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Clinical Diseases
5. Disseminated Infection/Bacteremia
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Bacteremia is rare d/t limited gonococcal ability to multiply in
bloodstream (NOTE: meningococcal multiply rapidly in the
blood)
Some gonococcal strain w/ ability to cause bacteremia
 Gonococci cross mucosal barrier d/t blood-barrier
breakdown; blood culture (+) for Gram (-) Diplococci
 Sx’s )Both male & female; m/c in females, though):
Fever; painful, purulent arthritis; small pustules on skin
scattered on a erythematous base – may develop into
necrosis
 Gonococcal = m/c cause of septic arthritis in
sexually active adults
Neisseriae
• NEISSERIAE GONORRHOEAE
– Clinical Laboratory Identification
• Males: numerous neutrophils )PMN’s( containing
Gram (-) diplococci in urethral exudate =
provisional Dx – start TX.
• Females: a positive gonococcal culture needed to
Dx infection
• If bacteremia suspected – additional cultures from
skin lesions, joint fluid, blood
Neisseriae
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NEISSERIAE GONORRHOEAE
– Clinical Laboratory Identification
1. Growth conditions
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Growth best under aerobic conditions
Most strains require enhanced CO2
N. gonnorrhoeae ferments glucose (not maltose,
lactose or sucrose)
Oxidase-positive
Mixed growth seen on plain Chocolate Agar medium
(non-selective medium)
Pure culture (selective growth) seen w/ Thayer-Martin
Chocolate Agar Medium – to isolate gonoccoci
Neisseriae
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NEISSERIAE GONORRHOEAE
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Clinical laboratory Identification
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Selective Media
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Thayer-Martin chocolate agar medium contains several antibiotics
that suppress the growth of non-pathogenic neisseriae and other
normal/abnormal flora
 Important medium for cultures obtained from GU tract & rectum
 Culture of N. gonorrhoeae on Thayer-Martin agar is the “goldstandard” for DX
Treatment & Prevention (diff to control b/c dis tied to sexual promiscuity)
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>20% of gonococcal isolates are resistant to penicillin,
tetracycline, cefoxitin, =/or spectinomycin
Penicillin-resistant organisms = Penicillinase-producing N.
gonorrhoeae
Tx w/ 3rd generation cephalosporins for uncomplicated infections
of urethra, endocervix or rectum
Abstinence, avoiding casual sexual contact, limiting # of sexual partners, taking birth
control measures (i.e., condom use)
Neisseriae
• NEISSERIA MENINGITIDIS
– One of the m/c causes of MENINGITIS
– Causative agent = N. meningitidis
– Infection can take form of fulminant
meningococcemia, w/ intravascular coagulation,
circulatory collapse, and potentially fatal shock (w/out
meningitis)
– Outbreaks common in winter & early spring; favored
by close contact
• Schools, institutions, military barracks
– N. meningitidis – afflicts young, previous well
individuals; and can progress to DEATH in hours
Neisseriae
• NEISSERIA MENINGITIDIS
– Structure of meningococci
• Non-motile, Gram (-) Diplococci; always found in
pairs
• Piliated – pili allow attachment to nasopharyngeal
mucosa, where organism it harbored in carriers
and those w/ disease.
• Encapsulated
– Meningococcal polysaccharide capsule =
antiphagocytic; most important VIRULENCE factor!
Neisseriae
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NEISSERIA MENINGITIDIS
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Structure of meningococci
1. Serogroups14 different capsular polysaccharide types
(LOS)
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Most infections w/ serogroups A, B, C, W and Y
 90% w/ A, B, and C
Serogroup A => massive epidemics in developing countries
Serogroup B => most predominant cause of disease and
mortality in US
2. Serotypes
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2nd classification sys: serotyping (1,2,3,….20)
 Serological, based upon properties of OMPs and LOS
Neisseriae
• NEISSERIA MENINGITIDIS
– Pathogenesis
• Maintenance of infection conferred by the
meningococcal capsule w/ antiphagocytic
properties
• LOS is released during autolysis & bacteial cell
division – toxic effects in disseminated dis.
• Production of IgA protease that cleaves human Ab
IgA – evasion of the IS response
Neisseriae
• NEISSERIA MENINGITIDIS
– Clinical Notes
• N. meningitidis – initial colonization w/in
nasopharynx, causing asymptomatic
meningococcal pharyngitis
• In young & immunocompromised, organism can
gain entry to bloodstream (disseminated dis or
bacteremia)  meningitis +/or fulminant
septicemia
• N. meningitidis = m/c cause of meningitis
Neisseriae
•
NEISSERIA MENINGITIDIS
–
Clinical Diseases
1.
Meningitis
•
•
•
•
•
•
•
Meningococci normally inhabit nasopharynx (barrier to the bacteria;
no blood entry)
If meningococci penetrate barrier and enter blood – can rapidly
multiply => Meningococcemia
Sx’s: fever, if not severe case
If organism crosses BBB and seed the meninges – multiply & induce
Inflammatory Response, accomp’d by influx of PMN Leukocytes
 result = purulent meningitis
Joint sx’s and petechial rash – common
After initial fever & malaise, severe HA, rigid neck (stiff neck &
back), vomitting & sensitivity to lights
Orthopedic Test: Kernig’s Sign
 A sx. of meningitis evidenced by reflex contraction & pain in
Hamstring m. when attempting to extend the leg after flexing the
thigh upon the body.
Neisseriae
•
NEISSERIA MENINGITIDIS
–
Clinical Diseases
2. Septicemia
•
•
•
Life-threatening in <12 hrs in healthy individuals
30% pts w/ meningitis progress into fulminant septicemia
 Severe septicemia & shock (exotoxin LOS responsible)
Seen mainly in very young children
 Waterhouse-Friderichsen Syndrome: an acute adrenal
insufficiency d/t hemorrhage into the adrenal gland
caused by meningococcal infection, characterized by:
large, purple, blotchy skin hemorrhages; vomiting and
diarrhea; circulatory collapse; necrosis of the adrenals;
death w/in 10-12 hrs.
Neisseriae
•
NEISSERIA MENINGITIDIS
–
Clinical Laboratory Identification
•
Gold standard for Dx of systemic meningococcal
infection is isolation of N. meningitidis from CSF
–
–
Under light microscope, specimens obtain from CSF or skin
lesion aspirates appear as Gram (-) Diplococci, often in
association w/ PMN leukocytes
Carriers: swab the nasopharynx
1. Culture Conditions
•
•
•
Chocolate Agar w/ increased CO2
Selective medium is NOT required b/c samples usually taken
from STERILE CSF
Thayer-Martin chocolate agar – needed for samples obtained
from skin lesions, nasopharyngeal swabs => eliminate contam
Neisseriae
•
NEISSERIA MENINGITIDIS
–
Clinical Laboratory Identification
2. Additional Tests
•
•
All Neisseria spp are Oxidase-positive
Differentiation between species, therefore, is by sugar
fermentation
•
•
•
N. meningitidis ferments BOTH glucose & maltose
N. gonorrhoeae ferments ONLY glucose
CSF in bacterial meningitis
 Increased pressure
 Elevated protein
 Decreased glucose (b/c of bacterial consumption)
 Increased # of neutrophils
Note: presence of the organism or of antigenic capsular
substance => confirms the DX
Neisseriae
•
NEISSERIA MENINGITIDIS
–
Treatment & Prevention
•
•
Bacterial meningitis is a Medical Emergency!!!
High fever, HA, and rash are tx’ed immediately to prevent
fulminant septicemia (i.e., to prevent DEATH)
–
•
1.
Penicillin G and ampicillin use; or cefotaxime or ceftriaxone
Diagnosis
•
2.
Confirmation of bacteriologic dx: too much time
Gram-stains of CSF, latex agglutination tests with serogroup specific
anticapsular Ab – for rapid presumptive Dx
Vaccines
•
Conjugate meningococcal vaccine (MCV4) approved in 2005 for use
in adolescents and adults 11-55 yoa
•
3.
Tetravalent vaccine w/ capsular polysacch’s from serogroups A,C, W-135,
and Y conjugated to the diphtheria toxoid – confers T-cell memory
Prophylaxis
•
Rifampin – usu. used to tx family members of an infected individual;
effective in eliminating carrier state