Bacterial Pathogenesis Mechanism in Bacteria (2024) PDF

1 Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran By; Dr. akbari 2024 Mechanisms of bacterial pathogenicity...

1 Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran By; Dr. akbari 2024 Mechanisms of bacterial pathogenicity 2 Bacterial pathogenicity Terms 3  The infection process The infection process induced by pathogenic bacteria are included;  Transmissibility  Entrance to host body  Attaching to host cells, usually epithelial cells  Invasion to host cells and tissues (direct and indirect) Toxigenicity  Evade or overcome on host defense  Multiplying and spread directly through tissues or via the lymphatic system to the bloodstream  Development of signs and symptoms of disease 4  Transmission of infectious pathogens A) Animal to human transmission - Salmonella and Campylobacter (food products). - Bacillus anthracis (anthrax) (Raw hair from infected animals). B) Animal arthropods to human transmission - Yersinia pestis (plague) (rodent fleas). 5  Transmission of infectious pathogens C) Human to human transmission 1- Direct contact  Hands (S. aureus)  Sexual contact 2- Indirect contact  Diarrhea (V. cholerae and E. coli )  Cough (M. tuberculosis)  Genital discharge  Environment contaminated objects 6 Bacterial entrance ways 7  Bacterial adherence to mucosal surfaces  Bacterial adherence to a eukaryotic cell requires two factors: a receptor and an ligand (adhesion).  The receptors are usually specific carbohydrate or peptide residues on the eukaryotic cell surface. 8  The mechanisms for adherence may involve two steps: 1. Nonspecific adherence: Reversible attachment of the bacterium to the eukaryotic surface (sometimes called "docking"). 2. Specific adherence: Irreversible permanent attachment of the microorganism to the surface (sometimes called "anchoring"). (lock-and-key bonds). 9  Forces involved in nonspecific adherence between bacterium and eukaryotic cell surface: 1. Hydrophobic interactions 2. Electrostatic attractions 3. Atomic and molecular vibrations resulting from fluctuating of dipolar molecules. 4. Brownian movement 5. Recruitment and trapping by biofilm polymers interacting with the bacterial glycocalyx (capsule). 10  Specific adherence  The adhesins of bacterial cells are chemical components of capsules, cell walls, pili or fimbriae.  The host receptors are usually glycoproteins located on the cell membrane or tissue surface. 11 12  Specific adherence of bacteria to cell surfaces  Direct evidence of specificity of adherence between bacteria and host cells are the following: 1. The bacteria will bind isolated receptors or receptor analogs. 2. The isolated adhesins or adhesin analogs will bind to the eukaryotic cell surface. 13  Examples of specific attachments of bacteria to host cell surfaces Bacterium Adhesin Receptor Attachment site Disease S. pyogenes Protein F Amino terminus of fibronectin Pharyngeal epithelium Sore throat S. mutans Glycosyl transferase Salivary glycoprotein Pellicle of tooth Dental caries S. salivarius Lipoteichoic acid Unknown Buccal epithelium of tongue None N-acetylhexos-amine-galactose S. pneumoniae Cell-bound protein Mucosal epithelium pneumonia disaccharide S. aureus Cell-bound protein Amino terminus of fibronectin Mucosal epithelium Various N. gonorrhoeae Type IV pili (N-methylphenyl- alanine pili) Glucosamine-galactose carbohydrate Urethral/cervical epithelium Gonorrhea ET E. coli Type-I fimbriae Species-specific carbohydrate(s) Intestinal epithelium Diarrhea UP E. coli Type I fimbriae Complex carbohydrate Urethral epithelium Urethritis UP E. coli P-pili (pap) Globobiose linked to ceramide lipid Upper urinary tract Pyelonephritis Whooping B. pertussis Fimbriae ("filamentous hemagglutinin") Galactose on sulfated glycolipids Respiratory epithelium cough V. cholerae Type IV pili (N-methylphenyl-alanine pili) Fucose and mannose carbohydrate Intestinal epithelium Cholera T. pallidum Peptide in outer membrane Surface protein (fibronectin) Mucosal epithelium Syphilis Mycoplasma Membrane protein Sialic acid Respiratory epithelium Pneumonia Conjunctival or urethral Conjunctivitis Chlamydia Unknown Sialic acid epithelium or urethritis 14  Specific adherence of bacteria to cell surfaces  Indirect evidence for specificity of adherence between bacteria and host cells:  S. mutans is abundant in dental plaque.  S. salivarius attached in high numbers to epithelial cells of the tongue but is absent in dental plaque. 15  Specific adherence of bacteria to cell surfaces  N. gonorrhoeae infections are limited to humans.  E. coli CFA I and CFA II infect humans.  E. coli K-99 strain infects calves.  Group A streptococcal infections occur only in humans.  Plasmodium vivax restricted to the Duffy antigens on the host's red blood cells. 16 Certain strains or races are genetically immune to a pathogen. For example;  Certain pigs are not susceptible to Enteropathogenic E. coli K-88 infections. 17  Invasion to host tissues  Invasion of bacteria to host tissues is performed by two mechanisms; 1- Production of extracellular substances (invasins) such as enzyme and toxins. 2- Direct interaction with the host cell. 18  Extracellular substances  Invasins which act against the host by breaking down primary or secondary defenses of the body.  Most invasins act locally to damage host cells and/or have the immediate effect of facilitating the growth and spread of the pathogen. 19  Different types of Invasins 1) Spreading Factors (bacterial enzymes) 2) Hemolysins and Leukocidins 3) Staphylococcal coagulase 4) Extracellular digestive enzymes 5) Toxins with short-range effects related to invasion 20  1. Spreading Factors  The “Spreading Factors” affect the tissue matrices and intercellular spaces, thereby promoting the spread of the pathogen. A) Hyaluronidase  Is produced by streptococci, staphylococci, and clostridia.  Attacks the interstitial cement of connective tissue by depolymerizing hyaluronic acid. B. Collagenase  Is produced by Clostridium histolyticum and Clostridium perfringens.  It breaks down collagen, the framework of muscles 21  1. Spreading Factors C. Neuraminidase  Is produced by V. cholerae and Shigella dysenteriae.  It degrades neuraminic acid (also called sialic acid), an intercellular cement of the epithelial cells of the intestinal mucosa. D. Streptokinase & Staphylokinase  Are produced by Streptococci and Staphylococci, respectively.  Kinase enzymes convert inactive plasminogen to plasmin which digests fibrin and prevents clotting of the blood. 22  2. Hemolysins and Leukocidins If they lyse Red Blood Cells they are sometimes called hemolysins. Leukocidins are able to lyse the white blood cells. Examples;  Leukocidins (staphylococci)  Alpha toxin (C. perfringens)  Lecithinases (C. perfringens)  Alpha toxin (staphylococci)  Streptolysin (streptococci ) 23  3. Staphylococcal Coagulase  Coagulase, formed by S. aureus, is a cell-associated (clumping factor) and diffusible enzyme that converts fibrinogen to fibrin which causes clotting.  Coagulase activity is almost always associated with pathogenic S. aureus and almost never associated with nonpathogenic Staphylococci. 24  4. Extracellular Digestive Enzymes  Extracellular enzymes including proteases, lipases, glycohydrolases, nucleases, etc., which are not clearly shown to have a direct role in invasion or pathogenesis.  These enzymes presumably have other functions related to bacterial nutrition or metabolism, but may aid in invasion either directly or indirectly. 25  5. Toxins with short-range effects related to invasion  Bacterial adenylate cyclase effects on host cells that promote bacterial invasion. Anthrax toxin (EF or Edema Factor) is an adenylate cyclase and causes increased levels of cyclic AMP and disruption of cell permeability.  The B. pertussis adenylate cyclase toxin may contribute to invasion through their effects on macrophages or lymphocytes. 26  Some extracellular bacterial proteins that are considered invasins Invasin Bacteria Involved Activity Hyaluronidase Streptococci, Staphylococci and Clostridia Degrades hyaluronic of connective tissue Collagenase Clostridium species Dissolves collagen framework of muscles Neuraminidase V. cholera and Sh. dysenteriae Degrades neuraminic acid of intestinal mucosa Coagulase S. aureus Converts fibrinogen to fibrin which causes clotting Kinases Staphylococci and streptococci Converts plasminogen to plasmin which digests fibrin Leukocidin S. aureus Disrupts neutrophil membranes and causes discharge of lysosomal granules Repels phagocytes and disrupts phagocyte membrane and causes discharge of Streptolysin S. pyogenes lysosomal granules Hemolysins Streptococci, staphylococci and clostridia Phospholipases or lecithinases that destroy red blood cells (and other cells) by lysis Lecithinases C. perfringens Destroy lecithin in cell membranes Phospholipases C. perfringens Destroy phospholipids in cell membrane 27  Directly invasion of bacteria into host cell  Direct invasion of bacteria into host cell is mediated by two different mechanisms;  “Zipper” invasion mechanism  “Trigger” invasion mechanism 28  “Zipper” invasion mechanism Step1; Bacteria commonly colonize on epithelial cells. Step2; High-affinity binding of bacterial surface adhesins to their receptors on mammalian cells. Step3; Initiating of cytoskeleton-mediated zippering of the host cell plasma membrane around the bacterium Step4; Subsequently the bacterium is internalized into a vacuole.  The “Zipper” mechanism is used by L. monocytogenes. 29  “Trigger” invasion mechanism Step1; The bacteria colonize on epithelial cells. Step2; The bacteria use type-III or type-IV secretion system to inject various effector proteins into the host cell cytoplasm. Step3;These factors activate of small Rho GTPases and cytoskeletal reorganization to induce membrane ruffling. Step4; As a consequence of this signaling, the bacteria are internalized into a vacuole.  The “trigger” mechanism is used by Shigella or Salmonella spp. 30  Evasion of host defenses Pathogenic bacteria to establish their infection in the host body needs to overcome the following items of the host defenses:  Overcoming host phagocytic defenses  Evading from complement cascade  Suppression the host immunological responses  Overcoming on Antibody-mediated Immunity (AMI)  Overcoming on Cell-mediated Immunity (CMI)  Inhibition of inflammatory responses 31  Overcoming host phagocytic defenses  Microbial strategies to avoid phagocytic killing are numerous and diverse, but are usually aimed at blocking one or of more steps in the phagocytic process. Recall the steps in phagocytosis: 1. Contact between phagocyte and microbial cell 2. Engulfment 3. Phagosome formation 4. Phagosome-lysosome fusion 5. Killing and digestion 32  1) Avoiding contact with phagocytes A) Entrance to inaccessible locations to phagocytes in the body such as internal tissues (e.g. the lumen of glands). B) Inhibit phagocyte chemotaxis  Streptococcal streptolysin suppresses neutrophil chemotaxis.  Clostridium θ toxin inhibits neutrophil chemotaxis. 33  1) Avoiding contact with phagocytes C) Hide the antigenic surface of the bacterial cell with a host component (self). Examples;  S. aureus produces cell-bound coagulase (clumping factor) which clots fibrin on the bacterial surface. T. pallidum binds fibronectin to its surface.  Group A streptococci are able to synthesize a capsule composed of hyaluronic acid. 34  2) Inhibition of phagocytic engulfment  Classical examples of antiphagocytic substances on the bacterial surface include:  Polysaccharide capsules of S. pneumoniae, H. influenzae, and K. pneumoniae.  M protein and fimbriae of Group A streptococci.  Surface slime (polysaccharide) produced by P. aeruginosa.  O antigen associated with LPS of E. coli.  K antigen of E. coli or the analogous Vi antigen of S. typhi.  Cell-bound or soluble Protein A produced by S. aureus. 35 Streptococcus pneumoniae, FA stain showing its antphagocytic capsule.  S. pneumoniae cells that possess a capsule are virulent; nonencapsulated strains are avirulent. 36  3) Survival inside of phagocytes  Some of survival mechanisms inside the phagocytes include: 1. Inhibition of phagosome-lysosome fusion This is the strategy employed by Salmonella, M. tuberculosis, Legionella and Chlamydia. 2. Survive inside the phagolysosome  B. anthracis, M. tuberculosis and S. aureus use this mechanism. 37  3) Survival inside of phagocytes 3. Escape from the phagosome The Rickettsias which produce a phospholipase enzyme that lyses the phagosome membrane within thirty seconds of after ingestion. 38  4) Products of bacteria that kill or damage phagocytes  Some of bacteria produce extracellular enzymes or toxins substances that is referred as aggressins directly attack and cause damage and kill the phagocytes. Phagocytes may be killed by aggressins before or after ingestion of the pathogen. 39 1. Killing phagocytes before ingestion  Streptolysin O binds to cholesterol in membranes of neutrophils and cause lysosomal granules to release. Staphylococcal leukocidin acts on the neutrophil membrane and causes discharge of lysosomal granules.  The exotoxin A of P. aeruginosa which kills macrophages.  The bacterial adenylate cyclases (e.g. anthrax toxin EF and pertussis AC) decrease phagocytic activity. 40 2. Killing phagocytes after ingestion  Some bacteria may grow in the phagosome or phagolysosome and release substances which can pass through the phagolysosome membrane and effect on other target sites in the cell. Examples;  Mycobacteria, Brucella, Listeria destroy macrophages. 41 42