| Abstract | Clostridium botulinum je anaerobna, Gram-pozitivna, sporulirajuća, štapićasta bakterija koja proizvodi vrlo jak neurotoksin. Spore su otporne na toplinu i mogu preživjeti u hrani koja nije dobro konzervirana. Postoji sedam tipova botulina (A, B, C, D, E, F i G), a razlikuju se po antigenskoj specifičnosti toksina koji proizvode različiti sojevi. Tipovi A, B, E i F uzrokuju botulizam kod ljudi, a tipovi C i D kod životinja. Do sada je zabilježeno samo nekoliko slučajeva trovanjem toksinom G tipa. Većina sojeva proizvodi samo jedan tip toksina, ali su zabilježeni slučajevi gdje jedan soj luči dva tipa toksina. Ovaj neurotoksinski kompleks se sastoji od BoNT asociranog s nekoliko različitih komponenti kao što su hemaglutinini (HA), netoksični nehemaglutininski proteini (NTNH), RNA i neke druge proteinske komponente. Geni koji kodiraju komponente ovog kompleksa su organizirani u klaster nazvan botulinski lokus, a njihova lokacija i kompozicija varira unutar različitih serotipova i sojeva. Geni su organizirani u dva policistronska operona (ntnhbont i ha operon). Geni koji razdvajaju ta dva operona kodiraju protein BotR/A koji djeluje kao pozitivni regulator ekspresije gena botulinskog lokusa. Pretpostavlja se da je on alternativni sigma faktor. Iz kulture C. botulinum tipa A mogu se izolirati tri kompleksa različite veličine 19S (900 kDa), 16S (500 kDa), 12S (300 kDa). Da bi mogao djelovati na ciljane stanice ovakav kompleks mora disocirati i osloboditi aktivni neurotoksin od 150 kDa. Na disocijaciju BoNT/A kompleksa utječe pH vrijednost, koncentracija proteina i prisutnost različitih soli. Botulizam je vrlo ozbiljna, ponekad i smrtonosna bolest koju uzrokuje neurotoksin botulin. Taj toksin preferentno djeluje na periferne kolinergične živčane završetke i blokira otpuštanje acetilkolina. Kada se toksin unese u probavni ili dišni sustav veže se na epitelne stanice odakle ulazi u krv i na kraju dopire do perifernih živčanih završetaka. Tamo se veže sa plazmatsku membranu, endocitozom ulazi u stanicu i pod utjecajem pH se translocira po endosomalnoj membrani. Otpuštanjem toksina u citosol, toksin djeluje kao metaloproteaza i cijepa polipeptide odgovorne za egzocitozu. |
| Abstract (english) | Clostridium botulinum is anaerobic, Gram-positive, spore-forming rod that produces a potent neurotoxin. The spores are heat-resistant and can survive in foods that are incorrectly or minimally processed. Seven types of botulinum are recognized (A, B, C, D, E, F and G), based on antigenic specificity of the toxin produced by each strain. Types A, B, E and F cause human botulism, types C and D cause botulism in animals. Only few outbrakes of type G have been reported. Most strains produce only one type of toxin, but strains producing dual toxin types have been reported. This neurotoxin complex is composed of the BoNT and several toxin associated proteins known as hemagglutinins (HAs) and the non-toxic non-hemagglutinin protein (NTNH), RNA, and other uncharacterized protein components. The genes encoding the neurotoxin associated protein components of the toxin complex are organized in a cluster called botulinum locus, and their location and composition varies among the different serotypes and strains. Genes are organized in two polycistronic operons (ntnh-bont and ha operons). The gene that separates the two operons encodes BotR/A protein, which is a positive regulator of the expression of the botulinum locus genes. BotR/A is possibly alternative sigma factor. Three different complex species with the discrete sizes 19S (900 kDa), 16S (500 kDa), 12S (300 kDa) may be isolated from C. botulinum type A cultures. To affect their target cells these complexes must dissociate realeasing the free 150 kDa neurotoxin. pH changes, protein concentration and precence of salts influence the dissociation of BoNT/A containing complex. Botulism is a serious, sometimes fatal, disease caused by a botulinum neurotoxin. This toxin, which acts preferentially on peripheral cholinergic nerve endings to block acetylcholine release. Toxin that is ingested or inhaled can bind to epithelial cells and be transported to the general circulation. Toxin that reaches peripheral nerve endings binds to the cell surface then penetrates the plasma membrane by receptor-mediated endocytosis and the endosome membrane by pH-induced translocation. Internalized toxin acts in the cytosol as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. |
