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MEKANISME PERUSAKAN TOKSIN BAKTERI

MEKANISME PERUSAKAN TOKSIN BAKTERI. Agustina Setiawati. PENDAHULUAN. Toksin : substansi terlarut yang dapat mengubah metabolisme normal sel host sehingga kondisi fisiologisnya jg berubah

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MEKANISME PERUSAKAN TOKSIN BAKTERI

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  1. MEKANISME PERUSAKAN TOKSIN BAKTERI AgustinaSetiawati

  2. PENDAHULUAN • Toksin : substansiterlarut yang dapatmengubahmetabolisme normal sel host sehinggakondisifisiologisnyajgberubah • Selpenghasil = bakteri, jugaberperandalamprosesygdisebabkanoleh protozoa, cacingdan fungi

  3. Toksinmikrobamenjadidibedakanmenjadi 2: 1. Eksotoksin 2. Endotoksin 3. Eksoenzim

  4. EKSOTOKSIN • Protein ygdiproduksiolehbakteri, baikygdiekskresikanatauterikatpadapermukaanbakteridandilepaskanketikabakterilisis. • Ditransportkedalamsel host • Mengubahfisiologidanmetabolismesel host • Umumnyaterdiridari sub unit A dan B • Contoheksotoksin: toksindiphteri, koleradan anthrax

  5. EKSOTOKSIN …. • Ekstoksinmasuksel host dgncara: 1) Receptor mediated endocytosis 2) Bergabungdenganlisosom 3) Suasanaasam pd lisosommemecahikatandisulfidadanmelepas sub unit A dalamsel 4) Sub unit A berperandalamberbagaitoksisitasintraseluler

  6. EKSOTOKSIN …. • Mekanismetoksisitasoleh EKSOTOKSIN ada 3: 1. Menghambatsintesis protein : toksindipteri 2. Hiperaktivitasekskresi: toksinkolera 3. Penghambatanaktivitas neurotransmitter: toksin tetanus

  7. ANTIGENIK EKSOTOKSIN • Eksotoksinbersifatantigenik Aktivitaseksotoksinditurunkanoleh antibody dalamtubuh host • Eksotoksintidakstabil, padasuatusaatsifattoksisitasnyahilangtetapitetapbersifatantigenik • Sifatinilahygdimanfaatkanutkpembuatan TOXOID • TOXOID: toksinygdilemahkantetapimasihmempunyaisifatantigenik (memacuproduksiantibodi). • Toxoiddigunakandalamimunisasi

  8. Corynebacteriumdiphtheriae • Corynebacteriumdiptheriae • Produces AB exotoxin • Gram positive rod w/ tapered ends • Significant cause of mortality until 1950s • Decline due to vaccination with toxoid (DPT) • Spread by close contact via droplets from human carriers or humans with active infection • Common location upper respiratory tract

  9. Sign and Symptoms • Local infection • Severe inflammatory reaction • Severe swelling in back of neck • Sore throat, nausea, vomiting • Formation of pseudomembrane • Systemic • Toxemia as toxin is absorbed from throat and carried by blood to target organs • Heart and nervous system

  10. MEKANISME AKSI TOKSIN DIPTERI • A subunit… • Mengaktivitas elongation factor-2) (EF-2) ygdiperlukanuntuksintesis protein

  11. Vibriocholerae • Vibriocholerae • Produces A + 5B exotoxin • Gram negative vibrio • Unusual disease • Cholerae does not invade tissue • Cholerae does not damage tissue • Lives in estuaries on copepods • Humans are incidentally infected when ingesting contaminated food or water

  12. Symptoms of Vibrio cholerae • Symptoms • Secretory or watery diarrhea • No blood in diarrhea • Large watery bowel movements • Loss of electrolytes • Muscle cramps • Low blood pressure • Rapid heart rate & feeble pulse • Vomiting • White blood cell count usually normal • Treatment • Usually self limiting symptoms as long as IV fluids are administered with oral rehydration solutions

  13. Clinical Manifestations www.who.int/entity/water_sanitation_health/dwq/en/admicrob6.pdf

  14. Treating Cholera Sack, David, et al. 2004. Seminar: Cholera. The Lancet. 363: 223-233.

  15. MEKANISME AKSI TOKSIN kolera

  16. Bacillus anthracis • Bacillus anthracis • Produces 2A + B exotoxin • Gram positive spore forming bacteria • Found in soil • Anthrax disease – direct exposure to spores • Inhalation – pulmonary • Ingestion – gastrointestinal • Invasion into surface wound – cutaneous • No cases involve person to person spread

  17. Sygn and mptomsof Bacillus anthracis • Cutaneous • Spores enter abrasions or cut in skin • Germination of spore causes local ulceration of the skin • Painless black eschar with edema • Antibiotics prevent invasion into blood stream • Usually heals completely without scarring

  18. Symptoms of Bacillus anthracis • Pulmonary • Life cycle • Macrophages engulf spores • Travel to nodes • Spores germinate en route • Cells are released spreading toxins and vegetative cells into the blood stream • Symptoms – caused by toxins • Fever and chills • Shortness of breath, & cough • Massive pleural effusions • Sepsis, shock & death

  19. MEKANISME AKSI TOKSIN antrak • Two primary toxins & capsule gene • All three genes are located on plasmids • Edema Factor A – toxin • Adenylylcyclase enzyme – increase in cAMP • Causes edema and pro-inflammatory response • Lethal Factor A – toxin • Metalloprotease • Cleaves MAP kinase required from cell division and signaling • Causes an overall suppression of immune system

  20. TRANSDUKSI SINYAL SELULER ADENILAT SIKLASE-cAMP

  21. MEKANISME AKSI TOKSIN antrak B. Anthracis EF LF B EDEMA Increased expression of pro-inflammatory mediators LF B EF B Endosome Acidic Environment EF cAMP B MAPK LF IMMUNE SUPPRESSION WBCs do not divide in the presence of pathogens; overall decrease in phagocytosis

  22. Clostridium tetanus • Clostridium tetanus • Produces AB exotoxin • Produces irreversible muscle contraction • Spastic paralysis • Symptoms result entirely from toxin • Anaerobic gram + spore forming rod • Lives in soil usually on rusty metal • Enters from puncture wound or cut • Organism does not spread form entry point • Begins with stiff back and neck muscles • Death results from respiratory failure

  23. MEKANISME AKSI TOKSIN tetanus • Menghambatpelepasan ‘inhibitory neurotransmitter ‘ yaitu GABA – aminobutyric acid γ

  24. ENDOTOKSIN • Endotoksin • Namaseringmenyebabkansalaharti • Toksintidakberadadalamselbakteri, tetapibagianmembranselbakteri • Toksinterletakpadabagianluarmembranselbakteri • Lipopolisakarida (LPS)bakteri gram - • Asamlipotekoat bakteri gram + • Toksikpadakonsentrasiygtinggi • Dapatdilepaskanolehbakterisaatlisis, spt: E.coli, Salmonella, Shigella, Pseudomonas, Haemophilus

  25. Menurunkansistemimun host • Mempunyaiefekfarmakologisygberbedapadakonsentrasirendahatautinggi

  26. Mechanism of Action of Endotoxins • Endotoxins bind to • Receptors on • Macrophages • Neutrophils • Lymphocytes • Proteins of complement • Complement is a group of proteins which circulate at constant levels in the blood • When activated complement is a powerful tool against invading pathogens • Increased inflamation, opsonization, & MAC

  27. Endotoksin • Host cell receptors (TLR) bind to endotoxin • TLR (Toll-like Receptor)

  28. Inflammation Opsonization MAC

  29. PIROGEN • Merupakansalahsatuendotoksin, adaygmenyebutkan ENDOTOKSIN=PIROGEN • Bagian Lipid A membranbakteri gram – • Potensilebihrendahdibandingkaneksotoksin • Aksitidakspesifik • Stabilterhadappemanasanselama 30’, • Tidakbersifatantigenik (tidakbisadiubahmenjaditoksoid)

  30. MEMBRAN SEL BAKTERI

  31. lipopolisakarida • Bagian paling luarmembransel • Total 3- 10% beratkeringsel • 3-4 jutamolekultiapsel • Bagianygdisebutpirogen: Lipid A • Lipid A menstimulasisistemimunmanusia

  32. MEKANISME AKSI PIROGEN • LPS terikatpada protein plasma LPS binding protein (LBP) • LBP berikatandgnreseptorpdmakrofagdanmonositsehinggamenyebabkan: 1. Produksisitokin (IL, TNF) memicuproduksiprostglandin & leukotrien  inflamasi 2. Aktivasikomplemen  pelepasanhistaminygmenyebabkanvasodilatasi 3. Koagulasi

  33. TES PIROGEN • Rabbit Pyrogen Test • Limulus AmoebocyteLisate Test

  34. Bacterial Exoenzymes • Enzimygdieksresikanbakteripadamatriksekstraselulersel, mempunyaiberbagaiaktivitas: • Merusakmembran • Merusakmembran sell host • Lisisseleritrosit • Merusakmatriksekstraseluler (fibronectin, kolagen & MMP) • Mengubahaktivitasobat co: Penisilanase (hidrolisispenisilin)

  35. αtoxin Pore forming toxin Common in Staphylococcus aureus Hemolysins Destroy red blood cells Streptolysins – group of hemolysins excreted by Streptococcus Streptokinase Attacks fibrin clots From Streptococcus pyogenes Hyaluronidase Breaks down hyaluronic acids in connective tissue Similar function for Collagenase Elastases DNase DNA is viscous Thins pus (DNA & debris) released from WBC EKSOENZIM

  36. Clostridium perfringens • Clostridium perfringens • Ananerobic gram + spore forming rod • Widely distributed in nature • Myonecrosis • Entry of spores by traumatic injury • Not highly invasive so it requires exoenzymes for a supportive growth environment • Exoenzymes • Lecithinase lipase c – major toxin • Lyses mammalian cells indiscriminately • Substrate is phophatidylcholine • Collagenase & hyaluronidase • DNAase

  37. TERIMA KASIH

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