Clostridia (G+) Flashcards
are clostridium aerobic or anaerobic?
strictly anaerobic
what gram classification are clostridium?
G+
clostridium species produce what?
ENDOSPORES and proteinaceous TOXINS that are responsible for disease symptoms
about how many species of clostridium are responsible for human infections?
~30
greater than how many species are found in environment (soil, water, animal wastes)
> 50
name 4 clostridium species and the disease they cause based on the toxin they produce
- c. difficile: pseudomembranous colitis (PMC)
- c. perfringens: cellulitis, gas gangrene, food poisoning
- c. botulinum: botulism
- c. tetani: tetanus
what is a spore?
form of bacteria that is metabolically inactive & coating that makes them very resistant, can remain viable for hundreds of years
which bacteria classes have the ability to produce endospores?
bacillus and clostridium
what adverse conditions are bacterial endospores resistant to?
extreme heat, drying, radiation, most chemical infections
what causes a pathogen to release spores?
spore induction caused by environmental unfavorable conditions (nutrient depletion)
how are spores formed for release?
bacteria creates membrane & engulfs
describe the structure of an endospore
outside surf=protein coat –>lipid mem–>cortex–>inner mem
what is the function of the endospore protein coat?
helps with heat resistance and drying
what is the function of the lipid membrane of the endospore?
helps with chemical sensitivity
is c.difficile easy to culture?
noooo “difficult clostrium”
what is pseudomembranous colitis?
yellow plaques containing fibrin and cellular debris in ulcers of colonic mucosa
what is c. difficile the leading cause of?
nosocomial diarrhea
where is c. difficile harbored in the human body?
harbored in a dormant state in the large intestine of small percentage of healthy humans in low numbers
how is c. difficile transmitted?
the endospore, hands of health care personnel
c. difficile has a disease state that is associated with what?
antimicrobial drugs, especially cephalosporins, ampicillin, and clindamycin
*get disease when on high dose of antibiotics
are the endospores formed by c. difficile resistant to antibiotics?
yes, only normal flora is killed
how do the spores infect?
spores vegetate, toxin production begins resulting in diarrhea
does invasion of the bowel wall occur with c. difficile?
no just like e. coli and v. cholerae
what do the two toxins do?
- changes function of epithelium cells
2. formation of pseudomembranous colitis
describe toxin A of c. difficile.
enterotoxin- fluid production and damage to the mucosa
describe toxin B of c. difficile.
cytotoxin-rounding of tissue-culture cells
where do both toxins act in the host cell?
in the cytoplasm of the host cell to glycosylate GTP-binding proteins (eg Rho, Rac)
- cell loses cytoskeletal structure and die
- on dead cell is accumulation of fibrogen and scar tissue
how is toxin A found?
ELISA detection of toxin A is diagnostic
where is c. perfringens found?
soil and intestinal tract of animals
environmental pathogen found in every soil except Sahara desert and sand
T/F: c. perfringens is a major pathogen of wound infections
TRUE; especially prevalent in war wounds
what kind of damage does c. perfringens cause?
local damage and systemic effects
- invasive properties
- due to variety of toxins produced
“spread through spore BUT toxin causes disease”
what severe conditions/trauma introduces spores from the environment to germinate?
anaerobic
compromised blood supply (main factor)
calcium ions
availability of peptides and amino acids
**all cause tissue damage
after the c. perfringen toxins are released what do they typically cause?
cellulitis that can lead to gas gangrene, a necrotizing, gas-forming process of muscle associated with systemic signs of shock
how many toxins does c. perfringen produce?
12
describe the alpha toxin (lecithinase) produced by c. perfringens?
- damages cell membranes, and cause gas gangrene
- phospholipase Type C
- hydrolyzes phsphatidylcholine and sphingomyelin that leads to cell death = DAMAGES PHOSPHOLIPIDS
- muscle tissue is destroyed (myonecrosis)
- reddish blue to black in color
- gas bubbles present
-shock and renal failure usually result and if untreated 100% fatality rate
how is c. perfringens treated and prevented?
- surgical removal of infected muscle
- antibiotics to control the infection, but surgery (amputation) still necessary
- antitioxin from horses, relatively little effect
- high oxygen concentrations: only subset of cases respond to
- prompt care is imperative: restore arterial blood supply
describe the c. perfringens food poisoning?
- 3rd most common type of food poisoning un US
- unrelated to gas gangrene
- sporulating c. perfringens that produce ENTEROTOXIN in intestine of people who have consumed contaminated food (usually meat)
- diarrhea in 12-24 hours
- self-limiting disappears in 1-3 days
where is clostridium botulinum found?
soils and marine sediments
what type of spores are produced by clostridium botulinum?
heat-resistant spores (not toxins) which often survive food processing
-germinate and grow under anaerobic conditions (such as in canned foods)
clostridium is the causative agent of what?
botulism:
-intoxication of ingestion of pre-formed toxin (don’t need the organisms to be present)
which species of clostridium is used as a bioweapon and bioterrorism threat?
clostridium botulinum
how many toxin serotypes are formed by c. botulinum?
8 neurotoxin (BoNT) serotypes A-G
among most poisonous substances know (lethal dose <1 microgram)
wish 3 c. botulinum neurotoxins are in fish and humans
A, B, E
purified BoNT is produced as a stable 900 kDa protein complex containing what?
- a 150 kDa toxic component
- a 750 kDa non-toxic component
*need both components to cause disease but 1 component is still toxic
what does c. botulinum toxin prevent the release of?
the release of acetylcholine neurotransmitter therefore interfering with neurotransmission at peripheral cholinergic synapses
what component of the c. botulinum toxin cleaves proteins involved in docking of neurotransmitter vesicles?
zinc metalloprotease
*NTs in vesicle wait to be released through exocytosis. vesicles have to dock with neuronal membrane and fuse with it then release through exocytosis. this prevents them from docking to synaptic membrane and prevents release of Ach.
what does c. botulinum toxin cause clinically?
flaccid paralysis within 12 to 36 hours
what does c. botulinum affect first?
- cranial nerves affected first
- double vision, difficulty swallowing
- paralysis descends to cause respiratory failure
name the 3 types of botulinum.
- food-borne botulism
- wound botulism
- infant botulism
what is food-borne botulism?
ingestion of preformed toxin in foods that have not been canned or preserved properly
MOST PREVALENT
what is wound botulism?
- systemic spread of toxin produced by organisms inhabiting wounds
- rare
- trauma, surgery, subcutaneous heroin injection, and sinusitis from intranasal cocaine abuse
what is infant botulism?
- intestinal colonization of organisms in infants younger than 1 year
- slow onset
- favorable outcome
- hypotonic (“floppy”) state
*don’t feed infants honey because of spores
how are c. botulinum infections treated?
- current mortality rate with good supportive care is 25%
- a trivalent antitoxin, isolated from horses, should be administered ASAP
- some muscles may be permanently damaged, and never recover because trouble releasing Ach
- no antibiotic necessary because not eating live bacteria, eating toxin
where is c. tetani located in humans?
ubiquitous in the GI tract of humans and animals
where environmentally is c. tetani located?
soils
T/F: c. tetani spores are not resistant to the environment
FALSE
what is c. tetani infection normally associated with?
traumatic wounds
where is a common location for germination of spores and production of c. tetani tetanus toxin?
neonatal contamination of umbilical cord at delivery
what is the c. tetani major toxin?
tetanospasmin
describe tetanospasmin.
- responsible for all symptoms
- 150 kDa protein
- heavy chain and light chain (A-B) connected by disulfide bridge (just like BoNT)
- individual chains are non-toxic
what is c. tetani tetanospasmin’s mechanism of action?
- attaches to peripheral nerves near wound and is transmitted to cranial nerve nuclei
- inhibits neurotransmitter release (GABA) and normal input
- result: reflex spasms, spastic paralysis
what is the function of GABA?
normally inhibitory, relaxes mm. contraction
what is c. tetani generalized tetanus and how can it affect the masseter mm.?
- trismus - “lock jaw” (80% of cases): tetanic spasm of masseter muscles that prevents opening of mouth
- descends to neck and back muscles and produces rigidity of abdomen and stiffness of extremities
- respiratory failure from paralysis of chest mm.
is c. tetani preventable? if so, then how?
- completely preventable with DPT vaccine
- diptheria pertussis tetanus vaccine
- tetanus toxoid (formalin-inactivated toxin that retains antigenicity)
how is c. tetani treated?
- human globulin sometimes given as passive immunization in “tetanus-prone wounds”
- antitoxin should be administered immediately, along with penicillin G to prevent further paralysis
- antibodies not produced due to low amounts of toxin present
- surgical debridement of the wound to prevent region of bacterial growth
how prevalent is mortality and what is it usually from in c. tetani infection?
11% mortality, usually due to respiratory failure
