L4 Mechanism of bacterial pathogenesis and virulence Fall24_a28bc1dca3c7bb5d420b5207c537489d.pdf

Mechanism of Bacterial Pathogenesis and Virulence MEDI 3104 Dr Zaaima AL-Jabri, MD, PhD Associate professor Dept of Micro...

Mechanism of Bacterial Pathogenesis and Virulence MEDI 3104 Dr Zaaima AL-Jabri, MD, PhD Associate professor Dept of Microbiology and Immunology Sultan Qaboos University © College of Medicine and Health Sciences Learning objectives Discuss the differences between commensals and pathogens. Explain the most common modes of transmission. Analyse differences in pathogenicity and virulence of pathogens infecting immunocompetent and immunocompromised host. Describe the bacterial cell structures, toxins and enzymes that aid in virulence and pathogenicity. Compare and contrast the function and role of different virulence factors in pathogenesis of disease. 2  Definitions-1 Commensals: Normal Flora Harmless microbes living on the host and causing no ill effect/injury to the host. Tas buy the best is healthy. Pathogens: Microbes capable of causing disease Infection: Growth and multiplication of a microbe in or on the body with or without the production of disease. infection mild no host disease, when immunitycan diser cause , Sometimes - Symptoms Colonization: & Microbe enters, multiplies, does not invade 3 Definitions-2 Pathogenicity: The capacity of a bacterium to cause disease. Virulence: The measure of the pathogenicity of a microorganism. - Invasiveness : The ability of the pathogen to invade the tissues. not on surface but inside cells tissme Opportunistic pathogens: Sick Cause disease in immunocompromised people (HIV, Solid organ transplant patient, Chemotherapy). immunocompetent wealthy Nosocomial infection: Hospital acquired infections. Iatrogenic infection: Physician induced. 4  I 3 2 Strict pathogens are more virulent and can cause diseases in a normal person. Opportunistic pathogens are typically members of normal flora and cause diseases when they are introduced into unprotected sites; usually occur in people with underlying conditions. immons compromised person 5 Stages of bacterial pathogenesis 1. Transmission 2. Adherence to cell surfaces 3. Invasion, Inflammation, & Intracellular Survival 4. Toxin Production eather both or T 5. Evasion of the host immune system 6  1. Modes of transmission-1 Entry into human body: ❖ Ingestion : (food or water) dirken ▪ Salmonella ▪ Shigella ▪ Vibrio Kills around 6 million children in a year - ❖Inhalation: ( Respiratory Tract ) - chest infection = 8 & ▪ Mycobacterium tuberculosis: 3 big small 3 travels long distase ▪ Streptococcus pneumoniae ▪ Haemophilus influenzae short distance Kills around 2 million people in a year 7 1. Modes of transmission-2 ❖Direct contact: ▪ Unclean hands: Common cold, skin and eye infections ▪ Break in the skin ( wounds): Staphylococcus aureus Y ▪ Burns: Pseudomonas aeruginosa G(f commensals ▪ Trauma (RTA) : Clostridium tetani 3 environment > - ❖ Sexual transmission: tetrances ▪ Neisseria gonorrhoeae ( gonorrhea ) ▪ Treponema pallidum ( syphilis ) ▪ Chlamydia trachomatis (Trachoma, urethritis) 8 1. Modes of transmission-3 to another ❖Blood borne transmission Blood transmitted ▪ Needle prick injuries / Blood transfusion / Intravenous drug abuse: ↳ with unsterile net HIV, HBV, HCV ▪ The screening of donated blood greatly reduced the risk of infection by these organisms. - ❖ Vector borne: transmitted b ee) mallaria (mosqitn) Mechanical: Flies spreading bacteria to food ( Salmonella/ shigella) Biological: Yersinia pestis multiplying in flea gut ❖ Vertical transmission: TORCH (from mother to fetus through placenta or breast milk) ▪ Toxoplasma ▪ Others: Treponema pallidum, varicella zoster virus ▪Rubella ▪Cytomegalovirus ▪Herpes simplex virus 9 Infective dose measurmet of virulance Low infective dose : Shigella ( Just 10 bacilli) & requires 6 No. I Resistant to stomach acidity cause bucteria to show disease Large infective dose: Vibrio cholerae 106-108 Srequires ↑ NO o bacteria 10 Infective dose > more - pathogenic 11  Colonization factors-1 Adherence attach it self to colonize Adherence of bacteria to epithelial / endothelial cells allows them to colonize the tissue. & 1. Pili (fimbriae) : binds to glycolipids or glycoproteins D to adhere/attach help bacteria 1. Adhesins : M protein in Streptococcus pyogenes, - 2. lipoteichoic acids in Gram positive bacteria - - 3. Biofilms : ( Adhere strongly to catheters, heart valves, S ( S knee joint replacement prosthesis) collection of plantonic cells Secrete materials to help bacteria to attach spreifent multiple organisms form layer 12 Colonization factors-2 Adherence- Biofilm Biofilms are dense, multiorganism layers of bacteria First layer of bacteria attaches directly to the surface of host cells Other layer of bacteria are attached to the basal layer by a polysaccharide matrix. Non cellular materials such as mineral crystals, corrosion particles, clay/silt or blood components are deposited depending on the envelope in which it develops. 13  Biofilm Formation indivichel bacteria & - a biofilm E I laye poly sachrich bacteria inside & Pathogens attach to the surface of the lumen in a central venous catheter and form colonies. Colonies grow and secrete a fibrous glycocalyx that protects the organisms from antibiotics. for ensures bacteria survives longer time 14 Biofilm formation on medical devices Biofilms as defense: protect bacteria from both antibiotics and host immune defenses such as antibodies and neutrophils. delay wound healing resulting in chronic wound infections, especially in diabetics. biofilm extracellular matrix improve adherence to the artificiula structure implant. inhabited by bacteria 15  3.Invasion-1 The ability of the pathogen to invade the tissues goes inside issurby - Enzymes Enzymes secreted secretedby byinvasive invasive Limiting phagocytosis by host immune bacteria: bacteria: system: 1. Collagenase Collagenasedegrade degrade collagen. collagen. 2. Hyaluronidase degrades Hyaluronidase degrades Capsule hyaluronic acid (e.g Strep pneumoniae and Neisseria hyaluronic acid 3. Coagulase meningitidis) 4. Coagulase Immunoglobulin A (IgA) - protease Immunoglobulin A (IgA) 5. protease Leukocidins Leukocidins strong capsule 16  3.Invasion-2 Bacteria release degradative enzymes, to breakdown host cells and tissues Collagenase, coagulase DNAase and hyaluronidase Coagulase produced by Staphylococcus aureus & Yersinia pestis. Converts fibrinogen to fibrin forming a clot & that protect bacteria from phagocytosis C. perfringens: Lecithinase and Cellulitis caused by Streptococcus collagenase I break down +issue pyogenes prevent clotting and skin very dep 17 3.Invasion-3 IgA: secretory antibody in the mucosal surfaces - protect epithelial surfaces from colonization and infection. Immunoglobulin A (IgA) protease: degrades IgA, allowing the organism to adhere to mucous membranes. 1. N. gonorrhoeae 2. H. influenza 3. S. pneumoniae 18  4. Toxin Production-1 Exotoxin not part of bacteria Endotoxin Released from the cell before or after lysis Integral part of cell wall Examples: Examples: I. Clostridium botulinum produces neurotoxin. II. Vibrio cholerae produces enterotoxin. D Endotoxin is LPS only o Protein Lipid A is the toxic component Heat labile-killed Heat stable stimulate immune by heat not nessesorly response & Antigenic and immunogenic* Antigenic; ??immunogenicity if available full for Toxoids can be produced** vaccinel No vaceins can Toxoids cannot be produced be formed endotoxic = y produce Specific effect on host - No Fever Many effects on host general effect ever Produced by gram positive and Gram negative bacteria Produced by Gram-negative bacteria only No fever Fever present *Immunogen is a stimulus that produces a humoral or cell-mediated immune response, whereas antigens are any substance that binds specifically to an antibody or a T-cell receptor. All immunogens are antigens, but all antigens may not be immunogens. **Toxoids (e.g. diphtheria, tetanus vaccine) are bacterial toxins that have been rendered non-toxic, but retain the ability to stimulate production of antitoxin. 19  4. Invasion/Toxin Production-2 Leukocidins: which can destroy both neutrophilic leukocytes and macrophages. cell to group causes immue lyse J A - Example: Panthon-Valentine leucocidin- (PVL) Secreted by Methicillin-resistant S. aureus (MRSA) plays major role in pathogenesis & 20 Genotypic virulence factors Plasmids: Confers additional properties such as: Drug resistance Foxing Bacteriocin production Toxigenicity Confer on the host bacterium survival advantage under appropriate conditions. Bacteriophage: a virus that infects bacteria * Transposons: DNA sequences that move from one bacteriophone like & uses bacterial wall location on the genome to another. - an causing infection * adds DNA to bacteria giving + features 21 References Michael R. Barer, Will L Irving, Andrew Swann, Nelun Perera. Title: Medical Microbiology, a guide to microbial infections Chapter 10 Bacterial pathogenicity Questions?! [email protected]