MEKANISME PERUSAKAN TOKSIN BAKTERI

Presentasi berjudul: "MEKANISME PERUSAKAN TOKSIN BAKTERI"— Transcript presentasi:

1 MEKANISME PERUSAKAN TOKSIN BAKTERI
Agustina Setiawati

2 PENDAHULUAN Toksin : substansi terlarut yang dapat mengubah metabolisme normal sel host sehingga kondisi fisiologisnya jg berubah Sel penghasil = bakteri, juga berperan dalam proses yg disebabkan oleh protozoa, cacing dan fungi

3 Toksin mikroba menjadi dibedakan menjadi 2:
1. Eksotoksin 2. Endotoksin 3. Eksoenzim

4 EKSOTOKSIN Protein yg diproduksi oleh bakteri, baik yg diekskresikan atau terikat pada permukaan bakteri dan dilepaskan ketika bakteri lisis. Ditransport ke dalam sel host Mengubah fisiologi dan metabolisme sel host Umumnya terdiri dari sub unit A dan B Contoh eksotoksin: toksin diphteri, kolera dan anthrax

5 EKSOTOKSIN …. Ekstoksin masuk sel host dgn cara:
1) Receptor mediated endocytosis 2) Bergabung dengan lisosom 3) Suasana asam pd lisosom memecah ikatan disulfida dan melepas sub unit A dalam sel 4) Sub unit A berperan dalam berbagai toksisitas intraseluler

6 EKSOTOKSIN …. Mekanisme toksisitas oleh EKSOTOKSIN ada 3:
1. Menghambat sintesis protein : toksin dipteri 2. Hiperaktivitas ekskresi: toksin kolera 3. Penghambatan aktivitas neurotransmitter: toksin tetanus

7 ANTIGENIK EKSOTOKSIN Eksotoksin bersifat antigenik
Aktivitas eksotoksin diturunkan oleh antibody dalam tubuh host Eksotoksin tidak stabil, pada suatu saat sifat toksisitasnya hilang tetapi tetap bersifat antigenik Sifat inilah yg dimanfaatkan utk pembuatan TOXOID TOXOID: toksin yg dilemahkan tetapi masih mempunyai sifat antigenik (memacu produksi antibodi). Toxoid digunakan dalam imunisasi

8 Corynebacterium diphtheriae
Corynebacterium diptheriae 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 Systemic
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) yg diperlukan untuk sintesis protein

11 Vibrio cholerae Vibrio cholerae 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
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
Unless otherwise noted, the information presented in the notes for this slide was assimilated from the website: After gaining entry into the host through ingestion, the organism colonizes the epithelial lining of the small intestine. The incubation period is one to five days, and patients are symptomatic for two to seven days. The production of Cholera Toxin, discussed in detail later, induces most of the symptoms associated with the disease cholera. For serious cases, death can occur as a result of hypovolemic shock (loss of vital organ function due to rapid fluid loss) within two to four hours of colonization. Two case types: Mild cases (90%) are difficult to distinguish from normal diarrheal diseases. Severe cases (10%) are associated with painless, watery diarrhea, with as much as 20 L day-1 fluid loss (Cotter, 2000) in as little as three to four hours, leading to hypovolemic shock. Severe dehyrdration results in muscle cramps, loss of skin turgor, scaphoid abdomen and weak pulse. ( 3. The onset of diarrhea in cholera allows for the rapid dissemination of copious quantities of this organism into the environment.

14 Sack, David, et al. 2004. Seminar: Cholera. The Lancet. 363: 223-233.
Treating Cholera Unless otherwise noted, the information in this notes section was assimilated from the website: Antibiotics are not necessary for most V. cholerae infections; however, they usually decrease the volume and duration of diarrhea and the period of Vibrio excretion. Antibiotics, when prescribed, should be ones to which the infective strain is susceptible because resistance is a growing problem. The susceptibility of infectious strains should be determined at the beginning of an epidemic using the standard disk diffusion test or by broth microdilution. For severe cases, tetracycline is the most-often prescribed antibiotic. Other antibiotics that are prescribed: cotrimoxazole, erythromycin, doxycycline, chloramphenicol, and furazolidone Sack, David, et al Seminar: Cholera. The Lancet. 363:

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 mptoms of 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 Adenylyl cyclase 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 decrease in phagocytosis
MEKANISME AKSI TOKSIN antrak B. Anthracis EF LF EDEMA Increased expression of pro-inflammatory mediators B LF B EF B EF Endosome Acidic Environment 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
Menghambat pelepasan ‘inhibitory neurotransmitter ‘ yaitu GABA – aminobutyric acid γ

24

25 ENDOTOKSIN Endotoksin Nama sering menyebabkan salah arti
Toksin tidak berada dalam sel bakteri, tetapi bagian membran sel bakteri Toksin terletak pada bagian luar membran sel bakteri Lipopolisakarida (LPS)bakteri gram - Asam lipotekoat  bakteri gram + Toksik pada konsentrasi yg tinggi Dapat dilepaskan oleh bakteri saat lisis, spt: E.coli, Salmonella, Shigella, Pseudomonas, Haemophilus

26 Menurunkan sistem imun host
Mempunyai efek farmakologis yg berbeda pada konsentrasi rendah atau tinggi

27 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

28 Endotoksin Host cell receptors (TLR) bind to endotoxin
TLR (Toll-like Receptor)

29 Inflammation Opsonization MAC

30 PIROGEN Merupakan salah satu endotoksin, ada yg menyebutkan ENDOTOKSIN=PIROGEN Bagian Lipid A membran bakteri gram – Potensi lebih rendah dibandingkan eksotoksin Aksi tidak spesifik Stabil terhadap pemanasan selama 30’, Tidak bersifat antigenik (tidak bisa diubah menjadi toksoid)

31 MEMBRAN SEL BAKTERI

32

33 lipopolisakarida Bagian paling luar membran sel
Total 3- 10% berat kering sel 3-4 juta molekul tiap sel Bagian yg disebut pirogen: Lipid A Lipid A menstimulasi sistem imun manusia

34 MEKANISME AKSI PIROGEN
LPS terikat pada protein plasma LPS binding protein (LBP) LBP berikatan dgn reseptorpd makrofag dan monosit sehingga menyebabkan: 1. Produksi sitokin (IL, TNF) memicu produksi prostglandin & leukotrien  inflamasi 2. Aktivasi komplemen  pelepasan histamin yg menyebabkan vasodilatasi 3. Koagulasi

35

36

37 TES PIROGEN Rabbit Pyrogen Test Limulus Amoebocyte Lisate Test

38 Bacterial Exoenzymes Enzim yg dieksresikan bakteri pada matriks ekstraseluler sel, mempunyai berbagai aktivitas: Merusak membran Merusak membran sell host Lisis sel eritrosit Merusak matriks ekstraseluler (fibronectin, kolagen & MMP) Mengubah aktivitas obat co: Penisilanase (hidrolisis penisilin)

39 EKSOENZIM α toxin Hemolysins Streptokinase Hyaluronidase DNase
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

40 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

41

42 TERIMA KASIH