Gram-positive bacilli and rods Katedra i Zaklad Mikrobiologii UM Wrocław Important terms .lysogenic bacteria .anatoxine -toxoid .active immunization .passive immunization .zoonosis Important terms - lysogenic bacteria Lysogenic bacteria - bacteria that is infected with a temporate bacteriophage and bacteriophage’s DNA is integrated into the bacteria's chromosome (viral genes are present in the bacterium without causing disruption of the bacterial cell) Important terms - anatoxine TOXOID TOXIN Toxicity Toxicity anatoxine = toxoid - bacterial toxin whoseAntigenicity toxicity has been weakenedAntigenicity or suppressed; can be used for safe active immunization Convertion : - heat Stimule active immunity - chemicals (toxoid vacines) Important terms – active immunization active immunization inactivated/killed- stimulation pathogen with a specific antigen to promotenon-virulent antibody or attenuated pathogen formation in the body.Bacterial Protection proteins or against disease may last several polysaccharides years, in some (Subunit/conjugate) cases for life toxoid Important terms - passive immunization Passive immunity - providing IgG antibodies to protect against infections (immediate, but short- lived protection) : a) natural passive immunity - maternal antibody (mainly IgG) protect the newborn baby b) acquired passive immunity - process of obtaining serum from immune individuals, andacquired then injecting it to protectnatural a susceptible person. Important terms - zoonosis zoonosis is any disease or infection that is naturally transmissible from vertebrate animals to humans as a result of direct or indirect contactwith animal population Gram-positive Rods Corynebacteria Not closely related Bacillus Listeria & Clostridium No cause similar clinical (spore forming bacteria) Erysipelothrix conditions do not produce spores Family: Bacillaceae - Cl. tetani Genus: - B. anthracis - Cl. botulinum Genus: - Cl. perfringens Bacillus - B. cereus - B. cereus Clostridium - Cl. difficile - product endoepores - Product endoepores - facultative or obligate aerobes - strict anaerobes - many produce antibiotics - diversity of anaerobic fermentation - Wide variety of extracellular enzymes (biodegradation & invasive infection) Bacillus anthracis • Protein capsule (poly-D-glutamic acid) • Form spores • Three toxin protein components (plasmid-coded ) Bioterrorism agent !!! individulal proteins important in pathogenesis of antrax • Protective antigen (PA) mediates cell entry of EF &LF • Edema factor (EF) severe edema (IL-4;disable immune response ) • Lethal factor (LF) tissue necrosis (TNF-α, IL1-β; kill the cell) Bacillus anthracis A-B toxines 2 A-B toxines, which share the same B component Lethal toxin Subunit A = rapid cell deth by cleaves critical intracellular signaling module Protective antigen Subunit B = binds toxin to host cells and mediates it internalization) Edema toxin Subunit A = catalyzes production of cyclic AMP within host cell -> dramatic tissue edema Anthrax • zoonosis disease • Is not spread from person to person How is anthrax spread? Getting spores in a Eating contaminated cut or broken skin meat Breathing in spores CUTANEOUS INHALATION INTESTINAL ANTHRAX ANTHRAX ANTHRAX Cutaneous Anthrax Symptoms • Develope 1-12 days • Begins like an insect bite • Becomes a fluid- filled blister • Center turns black and becomes sunken Inhalation Anthrax Symptoms • Incubation time: 1-5 days • Flu-like symptoms • Fever/ chills • Muscle aches • Malaise • Shortness of breath Flu symptoms vs Anthrax symptoms SYMPTOM FLU ANTHRAX Sore throat Common Occasional Runny nose Y N Fever and chills Y Y Cough, productive Y N Cough, dry, unproductive Y Y Schortness of breath Rare Common Chest pain rare common Intestinal Anthrax Symptoms • Nusea, loss of appetite • Vomiting • Fever • diarrhea Anthrax Therapy: – penicillin, tetracyclines, quinolones – administered before the onset of lymphatic spread! Prevention: – possible vaccination for „risk” groups – vaccination of animals (Pasteur 1881) – burning of burial of animals that died of anthrax Bacillus cereus infections Intravenus Occular infections Catheter related (necrotic toxine, cereolysine, sepsis phospholipase C) GASTROENTERITIS Emetic form Diarrheal form Heat-stable Heat-labile enterotoxine Proteolysis resistant (meat, vegetables) enterotoxin (Rice) intoxication infection caused by toxin producing in vivo Clostridium botulinum the bacillus of botulism • Found worldwide in soil and aquatic sediments • Botulus (Latin) = sausage • 15 min, 100°C – destroying of C.botulinum and its toxin • 121°C, 15 min (moist heat) – spores destruction CLASSIC BOTULISM Vegetables, fish contaminated with spores Toxine signs appear within 24h – 48h Improper Appropriate conditions: Toxin process of - Strictly anaerobic environment absorbtion food - Neutral or alkaline pH Spores germination Bacill multiplying Food is ingested Excrete toxin into the food Botulism failure of neurotransmission flaccid paralysis Botulinum toxin acts at the neuromuscular junction to prevent release of acetylcholine, a neurotransmitter that stimulates muscle contraction Manifestations of food-borne botulism • Very slight gastrointestinal symptoms • No fever, no sign of sepsis • Normal mental status • Descending flaccid paralysis with bulbar signs „4 Ds” –signs of botulinism 1. Diplopia (double vision) 2. Dysarthria (difficulty forming words) 3. Dysphonia (difficulty intoning words) 4. Dysphagia (difficulty swallowing) WOUND BOTULISM • Rare form of botulism • Wound becomes contamined with the organism, and toxin is absorbed from that site INFANT BOTULISM „ floppy baby syndrome” Early signs: - Constipation - Feeding problems - lethargy - Poor muscle tone Not only C.botulinum….. C. baratti, C.butyricum Botulism CLASSIC BOTULISM INFANT BOTULISM WOUND BOTULISM (intoxication) (infection caused by -toxin producing in vivo in toxin producing in vivo) the wound; - symptoms similar to those of foodborne infection - incubation period is longer_ Treatment • Antitoxin – trivalent horse antiserum (A, B, E) • Antibiotics ( infant and wound botulism) • Supportive measures (mechanical ventilation) Botulinum toxin and bioterrorism Lethal dose of toxin for a 70-kg human: - 0,09 to 0,15 µg intravenously - 0,70 to 0, 90 µg inhaled - 70 µg orally By contaminating food (unlikely) By inhalation (presence in aerosols) Medical uses of botulinal toxin • Dystonia • Strabismus • Hyperhydrosis Other: migraine headaches, achalasia, cerebral palsy Inhalational botulism does not occur naturally but would result from breathing in toxin used as a biological weapon Iatrogenic botulism - occur due to accidental injection into the blood stream of commercial botulinum toxin Clostridium tetani • Normal inhabitants of the herbivores • Produces a round terminal spore („drumstik”) • Do not invade but remain at the side of infection Clostridium tetani • Tetanolysin – hemolytic toxin • Tetanospasmin – neurotropic A-B toxin A – responsible for toxic effect B – binding subunit Tetanospasmin - Heat-labile, plasmid encoded – Produced during stationary phase of growth – Released when the cell is lysed – It is destroyed by: - heating (65°C, 5min) - action of acid - proteolytic enzymes Tetanospasmin - Being internalized & moves from the peripheral nerve terminals to the central nervous system by retrograde axonal transport – Being released from the postsynaptic dendrites – Localized within vesicles in the presynaptic nerve terminals – Acts by blocking the release of inhibitory neurotransmitters (GABA) – Causing exitatory synaptic activity to be unregulated Tetanus Predisposing factor for tetanus: - area of low oxidation-reduction potential (necrosis, large splinter) - coinfection with aerobic organisms - others:unskilled abortion, scarification rituals, female circumcision Tetanus - generalized - localized - cephalic - neonatal Tetanus Incubation period: 4 days- several weeks • Tingling sensation in the vicinity of the wound • Muscular spasms • „ lockjaw” • Risus sardonicus -„sardonic grin” • opisthotonus Treatment • Surgical management • Tetanus toxoid – active immunisation • Passive immunisation with antitoxin • Critical care unit Complications of Tetanus •Laryngospasms •Fractures •Hypertension •Nosocomial infections •Pulmonary embolism •Aspiration pneumonia •Death Clostridium perfringens • Part of normal flora (vagina, GI) • Ubiquitous in nature • Cl. perfringens strains are grouped A through E type Pathogenesis Exogenic infection: Endogenic infection: penetrating wound, after gut rupture, septic contaminated with spores abortion (rare) Clostridium perfringens Remember, sometimes just colonization After: - gut rupture - septic abortion GASTROENTERITIS SOFT TISSUE INFECTIONS SEPSIS MYONECROSIS NECROTIZING FOOD CELLULITIS ENTERITIS POISONING FASCIITIS SOFT TISSUE INFECTIONS CELLULITIS FASCIITIS MYONECROSIS = suppurative myositis = gas gangrene edema results from cellulitis erythema systemic spraed Accumulation of pus gas formation in tissue necrosiss of muscle generally nonpeinful in the muscle planes no necrosis painful no sistemic symptoms gas formation LOCALIZED ! SYSTEMIC ! -> shock, renal failure Clostridial cellulitis • No systemic toxemia • Infected tissue looks similar to gas gangrene due to gas bubbles fermentation Myonecrosis (gas gangrene) Is marked by: high fever intense pain brownish pus gas bubbles (CO2, H2S, CH4) skin decoloration foul odor Clostridium perfringens soft tissue infections - Typically polymicrobic: Cl. perfringens (10-48h) Cl. septicum (2-3 days) Cl. histolyticum