Clostridium Grampositive large rods Gramvariable

1
Clostridium Gram-positive large rods
(Gram-variable) motile endospores
produced anaerobic, catalase negative
carbohydrates fermented to acids, alcohols and
acetone gas (CO2 , H2 and CH4 ) often
produced proteins hydrolyzed and amino acids
fermented - putrefaction Stickland reaction
oxidation of one, reduction of another
habitats soil to intestinal tract of man and
animals exotoxins and exoenzymes important
factors Species distinction spore location
and shape protein, amino acid and
carbohydrate metabolism action on milk
stormy fermentation more
2
Virulence factors protease collagenase,
elastase lipase phospholipase (a-toxin,
phospholipase C, lecithinase) cytolysin
promotes vascular injury (C. perfringens) at low
concentrations activates neutrophils which
adhere to capillary wall, causing decreased blood
flow and hypoxia activates TNF-a, IL-1,
IL-6, platelet activating factor, resulting
in shock
3
Virulence factors enterotoxin (Toxin A in
C. difficile) causes fluid accumulation in
bowel cytotoxin - causes inflammatory
response induces release of TNF-a, IL-1 IL-6
by leukocytes (toxin B in C. difficile)
4
Botulinum toxin 7 serotypes A to G A
B - botulism in humans progenitor toxin
complex activated in GI tract botulinum
toxin several other proteins complex
protects from stomach acid proteases active
toxin composed of 2 polpeptide chains 50 Kd
and 100 Kd peptides held by S-S bonds (formed
as 150 Kd protein) 50 Kd binds neuronal
endings, both autonomic somatic toxin
internalized prevents neurotransmitter release
paralysis toxin may be zinc protease which
cleaves vesicle proteins called
synnaptobrevins
5
Toxin C2 A-B type toxin, 150 Kd B portion
binds to variety of cells A portion ADP-R
activity for actin affects microfilament
formation toxin increases vascular
permeability resembles enterotoxin fluid
into small intestine Toxin C3 ADP-R activity
for GTP-binding protein proteins involved
in signal transduction affects many regulatory
activities role in pathogenesis unknown
6
Food poisoning C. perfingens beef,
turkey, chicken most frequent food cooked in
bulk, not hot enough, kept warm too long spores
ingested (food with toxins not palatable) toxin
causes watery diarrhea, cramps aerotolerant ova
l subterminal spores ferments sucrose strong
gas production in soil, intestinal tract of
humans animals
7
Food poisoning C. perfingens two toxins
active in tissues a-toxin (phospholipase C
or lecithinase) enterotoxin
(heat-labile) part of spore coat causes
decrease in glucose transport intestinal
epithelial damage protein loss into
lumen watery diarrhea, severe abdominal
cramps 24-hr duration
8
Food poisoning C. botulinum blood sausage
botulus sausage 3 types food borne,
wound, infant wound drug abuse (needle site),
nasal/sinus (cocaine) infant ingest
spores (honey) diminished suckling, ability to
cry neck and peripheral weakness, respiratory
failure food borne improperly preserved
food mild dryness of mouth, blurred vision,
double vision severe difficulty speaking,
swallowing muscle weakness very severe
difficulty breathing
9
C. tetani tetanus in writings of
Hippocrates organism described in 1880s
toxoid first used in 1920s spores deep in
tissue low O2 incubation period 3 days
to 3 weeks
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C. tetani tetanus two toxins tetanolysin
O2-sensitive hemolysin tetanospasmin
produced in log phase of growth released by
autolysis human lethal dose lt2.5 ng/kg
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C. tetani tetanus two toxins tetanospasmi
n 150 Kd polypeptide cut to two peptides
held by 2 S-S bonds B portion binds to
cells A portion has ADP-R activity for
actin binds motor end plate, internalized move
s to ventral horn of the spinal cord prevents
the release of glycine GABA disinhibition
of spinal cord reflex arcs excitatory
reflexes multiply unchecked
12
C. tetani tetanus three forms 1.
localized painful spasms in area around
injury 2. generalized 80 of cases
risus sardonicus sardonic laugh/smile
characteristic facial expression raised
eyebrows, tight closure of eyelids, wrinkling
of forehead, extension of corners of mouth,
muscle spasms in all muscle groups - glottis
involvement death autonomic nervous
system hypotension or hypertension tachycardia
and arrhythmias
13
C. tetani tetanus three forms 3.
cephalic injury to head or face short
incubation, 1-2 days nerve palsies of
several cranial nerves followed by
generalized tetanus
14
Gas gangrene surgical procedures resulted in
massive necrosis and gangrene War of
1914-1918 renewed study 1914 12 of wounded
developed gangrene 20-25 died 1918
incidence way down wound contaminated with
many organisms aerobic anaerobic anaerobes
cause disease
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Gas gangrene C. welchii, C, perfringens, C.
sporogenes, C. histolyticum ferment
sugars and more to lactic acid and gas gas
pressure decreases blood flow control by
tissue excision and antibiotics serious cases
require hyperbaric therapy C. perfringens
may get to gall bladder cholecystitis gas-fille
d gall bladder