BAKTERI PENGHASIL TOKSIN

Dr Ance Roslina,M.Kes
Departemen Mikrobiologi FK UMSU
2017
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What makes a pathogen?

Virulence Factors
Factors that improve attachment
Pili, capsules, fimbriea
Factors that allow penetration
Enzymes- hyaluronidase, proteases
Factors that improve colonization
Siderophores

Toxins- damage host

BACTERIAL TOXINS
Toksin adalah suatu zat dalam jumlah relatif kecil yang apabila masuk
ke tubuh manusia akan bereaksi secara kimiawi dapat menimbulkan
gejala abnormal hingga menyebabkan kematian.

Bacterial toxins are exotoxins and endotoxins.

Bacteria
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Toxins
EXOTOXINS
Exotoxin producing bacteria
1. Corynebacterium diphtheriae. Strains that carry a temperate bacteriophage are
toxigenic causes diphtheria. Exotoxin inhibits protein synthesis and causes cell
death. Causes diphtheria.
2. Clostridium tetani. Exotoxin blocks action of inhibitory neurones of spinal cord.
Causes tetanus.
3. Clostridium perfringens. (a) Causes gas gangrene. Exotoxin (alpha toxin) has
lacithinase activity and thereby causes cell death, (b) Enterotoxin causes hyper
secretion of water and electrolytes in diarrhoea.
4. Clostridium botulinum. Exotoxin causes paralysis of deglutination and
respiratory muscles. It blocks release of acetylcholine of synapses and
neuromuscular junctions. Causes botulism.
EXOTOXINS
5. Vibrio cholerae 01 and 0139. Enterotoxin (Exotoxin) causes hyper secretion of water and
electrolytes within gut in diarrhoea.
6. Enterotoxigenic E. coll. Produce enterotoxin (LT- heat labile exotoxin) causes hypersecretion of
water and electrolytes within gut.
7. Shigella dysenteriae type 1 (Shiga bacillus). Exotoxin causes acute inflammation.
8. Staphylococcus aureus- some strains : (a) Toxic shock syndrome toxin-1. Causes toxic shock
syndrome. (b) Staphylococcal enterotoxin causes toxin type food poisoning and stimulates vomiting
centre of brain.
9. Streptococcus pyogenes. Pyrogenic (Erythrogenic) exotoxin causes scarlet fever and toxic shock
syndrome.
NOTE : Enterotoxins are exotoxins that are associated with diarrhoea) diseases and food poisoning.
Bacteria producing enterotoxins are V. cholerae, enterotoxigenic E. coli (ETEC), some strains of S.
aureus, V. parahaemolyticus, Y. enterocolitica, Aeromonas species, and C. perfringens.
 Toxoid. Toxoid is modified exotoxin. An exotoxin has two main properties :
(1) toxicity, and
(2) antigenicity. In toxoid, the toxicity of the toxin is destroyed but its
antigenicity is preserved. As such toxoids e.g. diphtheria toxoid, tetanus
toxoid can be safely used for vaccines. Toxins can be converted to toxoid by
different methods e.g. formalin treatment.
 ENDOTOXINS
Endotoxins are the integral part of the cell walls of Gram-negative bacteria, and are
liberated when bacteria are disintegrated (lysed). Cell wall of Gram negative bacteria
contain lipopolysaccharides (LPS, endotoxin) which consists of : (1) Lipid A. This is the
endotoxin and is the core, and (2) Polysaccharide form coat. This is the 0 antigen which can
induce specific immunity. Physiological, pathological and clinical effects of endotoxins of
different Gram negative bacteria are similar. These are :

1. Fever. The endotoxin acts on mononuclear phagocytes (monocytes/macrophages), with

liberation of interleukin-1 (endogenous pyrogen). Interleukin-1 acts on thermoregulatory
centre. Chill is due to widespread arteriolar and venular constriction.
2. Leucopenia occurs early with onset of fever. It may be followed by leucocytosis.

3. Hypoglycaemia. LPS enhances glycolysis in many cell types and can lead to
hypoglycaemia.

4. Hypotension occurs early in Gram-negative bacteraemia.

ENDOTOXINS
5. Shock. 'Endotoxic' or 'septic' shock may develop in severe Gram-negative bacteraemia (See
chapter 4).
6. Activation of complement. Endotoxin activates complement system by alternative pathway.
7. Disseminated Intravascular Coagulation (DIC). DIC may occur in Gram negative bacteraemia. It is
initiated on activation of factor XII (Hageman factor) of coagulation cascade by endotoxin which
finally leads to conversion of fibrinogen to fibrin. Endotoxin leads platelets to adhere on vascular
endothelium. Endotoxin can activate plasminogen to plasmin which acts on fibrin producing fibrin-
split products. Shwartzman phenomenon is taken as a specialized form of DIC.
8. Death may occur due to shock and/or DIC.

NOTE: Peptidoglycan of Gram-positive Bacteria: Peptidoglycan of Gram-positive bacteria released

during infection may produce similar activities as LPS of Gram-negative bacteria.
However, peptidoglycan is much less potent than LPS.
Characteristics and Differences of Exotoxins
and Endotoxins
Endotoxin:
1. Integral part of the cell wall of Gram-negative bacteria. Released on bacterial
death and in part during growth. Release is not required for biologic activity.
2. Formed only by Gram-negative bacteria
3. Lipopolysaccharides. Lipid A portion is responsible for toxicity.
4. No specific receptor.
5. Moderately toxic. Fatal to animals in large doses.
6. Relatively heat stable. Toxicity is not destroyed above 60C for hours.
7. Weakly antigenic. Antibodies are protective.
8. Not converted to toxoid.
9. Synthesis directed by chromosomal genes.
10. Usually produce fever in the host by release of interleukin-1 and other
mediators..]
Exotoxins:

1. Excreted by living cells

2. Produced by Gram-positive and Gram-negative bacteria
3. Polypeptides
4. Usually bind to specific receptors on cells
5. Highly toxic. Fatal to animals in very small doses
6. Relatively heat labile. Toxicity destroyed over 60C
7. Highly antigenic. Stimulate formation of antitoxin. Antitoxin neutralizes
the toxin
8. Converted to toxoid by formalin. Toxoid is nontoxic but antigenic. Toxoids
are used to immunize, e.g. tetanus toxoid
9. Usually controlled by extra-chromosomal genes, e.g. plasmids, phage
gene
10. Usually do not produce fever in the host.
C.tetani
Mekanisme kerja toksin tetanus:
1. Jenis toksin Clostridium tetani menghasilkan tetanolisin dan
tetanospasmin.
Tetanolisin mempunyai efek hemolisin dan protease, pada dosis
tinggi berefek kardiotoksik dan neurotoksik.

Tetanospasmin mempunyai efek neurotoksik, tetanospasmin bekerja

pada ujung saraf otot dan sistem saraf pusat yang menyebabkan
spasme otot dan kejang.
 2. Toksin tetanus dan reseptornya pada jaringan saraf berkaitan
dengan gangliosid ujung membran presinaptik, baik pada
neuromuskular junction, mupun pada susunan saraf pusat.
Ikatan ini penting untuk transport toksin melalui serabut saraf,
namun hubungan antara pengikat dan toksisitas belum
diketahui secara jelas.
Tetanus
Ada dua hipotesis tentang cara bekerjanya toksin, yaitu:
1. Toksin diabsorbsi pada ujung syaraf motorik dari melalui sumbu
silindrik dibawa kekornu anterior susunan syaraf pusat
2. Toksin diabsorbsi oleh susunan limfatik, masuk kedalam sirkulasi
darah arteri kemudian masuk kedalam susunan syaraf pusat.
 Diphtheria (Corynebacterium diphtheriae)

Gram positive, rod-like organism

Bacterial disease caused by a secreted exotoxin.
Spread via airborne respiratory droplets
Exotoxin destroys underlying tissue, forming a
tough, fibrous membrane compose of fibrin,
white blood cells and dead respiratory cells
Also responsible for systemic manifestations.
Clostridium botulinum

Spora bakteri ini tersebar di alam, daerah pertanian dan tanah hutan,
danau, pada saluran pencernaan ikan, kepiting, dan mamalia.
Toksin yang diproduksi bakteri ini disebut toksin A-B (tipe III) toksin
yang mempunyai target di sel neuron/saraf, memblok kerja
neurotransmiter asetilkolin, sehingga timbul paralisis flasid terutama
neuron perifer.
Masa inkubasi; 4 jam- 8 hari (biasanya 18-36 jam). Gejala awal timbul
vertigo, lemah lesu, penglihatan kabur, lama-lama kesulitan berbicara,
menelan dan bernafas, abdominal distensi, dan akhirnya paralisis lalu
dapat menimbulkan kematian.
Bacillus cereus
Keracunan makanan (emetik dan diare)
Toksin (enterotoksin) intoksikasi
Organisme tanah yang mengkontaminasi beras
Spora bcereus tumbuh dan sel vegetatif menghasilkan toksin
selama sporulasi
MI: emetik (1-5 jam), diare (1-24 jam)
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Virulence factors important in Salmonella pathogenesis

Mycotoxin:
Mycotoxin is secondary metabolites produced by fungi that are capable of
producing disease in human and animals.
The term "mycotoxin" is produced by fungi during their colonization in crops.
One species of the mold may produce different types of toxin and the same toxin
may produce different species.
They cause abnormalities in cells metabolism, the reproductive process which
alters the functions of kidney, liver, lungs, etc.
 Food most susceptible to fungi producing mycotoxins includes:
corn,
wheat,
barley,
peanuts, etc
Some important mycotoxins include:
1. Aflatoxin (Aspergillus flavus, Aspergillus bombycis )
2. Patulin (Penicillium verrucosum, Penicllium expansium)
3. Ochratoxin (Aspergillus ochraceus)
4. Penicillinic acid (Penicllium puberelum)