Lecture 10-Bacterial Toxins

7/24/2019 Lecture 10-Bacterial Toxins

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Bacterial ToxinsEndotoxin: cell associatedExotoxin: secreted from the cellLipopolysaccharide (LPS) example of an endotoxin

LPS coats the outer membrane of gram negative bacteria

LPS can be shed from the ! of gram negative bacteria in ! derived vesicles or ! fragmentsLPS is composed of lipids and sugars Three components are antigen" core" and Lipid #

Lipid # is the toxic component of endotoxin The antigen is not a protein and is uni$ue to each bacterial specie

%eat does not easily inactivate the function of endotoxin compared toexotoxinThe receptor for LPS in humans is the toll li&e receptor ' (TL ') TL ' can be found on variety of cells including macrophages and

endothelial cells LPS TL ' binding induces a variety of responses depending on the cell

(pro inflammatory cyto&ine release causing endotoxic shoc&)Sepsis: an example of endotoxic shoc&

ver *+,",,, cases per year in the -nited States of .hich / die of shoc& 0an be caused by all &inds of microbes

elated to mass replication of microbes in bloodEndotoxic shoc& is 1ust one type of septic shoc& Symptoms: fever" hypotension" inflammation" increased antibody production" vasodilation" organ failure" intravascular coagulation

2ntravascular coagulation is bleeding into tissue causes blood clots to form .hich can damage tissue due to bloc&age of normal blood flo.

Then overtime clotting proteins in the blood are consumed increasing theris& of serious bleeding from even minor in1uries


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#n example is 3eisseria meningitidis septicemia .hich causes disseminatedintravascular coagulation

ExotoxinsSecreted

0ytotoxins: cause cell damagePore forming toxins: causes cell lysisExoen4ymes: alter normal cell functionSuperantigens: cause release of vast amounts of cyto&ine and nonspecificactivation of T cells!any others56ey point: The microbe that releases the exotoxin can be distal from the site ofthe exotoxin action because the exotoxins are secreted and circulated in the body

Properties of Exotoxins-sually proteins and usually en4ymes%ave highly specific targetsSecreted: can affect tissues located a.ay from site of bacterial coloni4ation!any exotoxins are #B toxins #ntibodies can be used to counteract exotoxins

3eutrali4ing the toxin7s en4ymatic activity Prevent receptor recognition and upta&e of exotoxin into the cell by binding tothe toxin

#B toxinsExotoxins are typically #B toxins though they can also be directly in1ected intocells by a type 222 secretion systemThe # (active) subunit is en4ymatically active and is responsible for the toxic

activity The B (binding) subunit mediates binding to the receptor on a target cell

The B subunit is .hat determines the cell and tissue specificity of an exotoxinThe #B toxin is brought into the cell by receptor mediated endocytosis

nce in the cytosol the endosome acidifies .hich causes the release of the #subunitThe # subunit exits the endosome and carries out its toxic function


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esponsible for &no.ing three exotoxins8iphtheria toxin (#B toxin) %as 9 # subunit and 9 B subunit0holera toxin (# +B toxin) %as 9 # subunit and + B subunits #nthrax toxin (;# B toxin)

%as ; # subunits and 9 B subunit%olo toxin: any toxin .hose structure is composed of several subunits

8PT (also 8TaP) vaccine8PT vaccine given to protect against three diseases: diphtheria" pertussis" andtetanus8iphtheria and tetanus are both mediated by only one toxinPertussis is mediated by more than one toxin as .ell as other factors

8iphtheria bac&ground #ncient disease that has been present throughout history

8iphtheria infections predominant in young children of children under the age of 9, died in 3e. England2n 9?;,s -S" 9,, ;,,& cases per year and 9= 9+& deaths per year8iphtheria is no. rare due to mass vaccination0ase fatality is + 9,> do.n from +,> .hich .as the rate before the advent ofantitoxins and antibiotics

8iphtheria clinical informationTransmission: direct contact .ith infected people or their bodily fluids0lassic diphtheria is caused by 0orynebacterium diphtheriae0oloni4ation of the pharynx by 0@ diphtheriae results in pharyngitis .hich is theinflammation of pharynx resulting in the characteristic Abull nec&8iphtheria can also cause cervical edema2n the pharynx" a pseudomembrane forms induced by diphtheria toxin (8T)

Pseudomembrane is bluish grey in colorPseudomembrane is composed of fibrin" bacteria" inflammatory cells" and celldebrisThe pseudomembrane is responsible for respiratory obstruction .hich cancause death

8T spreads systematically in the body affecting multiple organ systems!yocarditis (inflammation and damage of heart muscle) in heartParalysis (spread to central nervous system)

There is also a cutaneous form of diphtheria .hich coloni4es nasal cavity" larynx"or less commonly the s&in%o. to diagnose diphtheria

Loo& for symptoms such as Abull nec& " cervical edema" pseudomembrane(difficulty in breathing)Ta&e a s.ab of pharynx to culture bacteria and test for presence of diphtheriatoxin


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%o. to treat diphtheriaTreat .ith antibiotics Erythromycin PenicillinTreat .ith antitoxins #ntitoxin is obtained from the serum of horses immuni4ed .ith diphtheria

toxoid Toxoid: a toxin .hose toxicity has been inactivatedCsuppressed chemically

(formalin) or by heat" but still is immunogenic (can elicit an immuneresponse)

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Lecture 10-Bacterial Toxins