Lectures in General Microbiology PDF

Lectures in General Microbiology GEMERLYN G. GARCIA, DVM, MSc, PhD  VIRULENCE as a PHYSIOLOGICAL PROBLEM Virulence a measure of the pathogenicity of an organism Its degree is related to the ability of the organism to cause a disease despite host resistance mechanisms. T...

Lectures in General Microbiology GEMERLYN G. GARCIA, DVM, MSc, PhD  VIRULENCE as a PHYSIOLOGICAL PROBLEM Virulence a measure of the pathogenicity of an organism Its degree is related to the ability of the organism to cause a disease despite host resistance mechanisms. This is affected by numerous variables number of infecting bacteria route of bacterial entry into the body specific and non-specific host defense mechanisms virulence factors of the bacterium Pathogenesis refers to the mechanism of infection and to the mechanism by which a disease develops results from a disturbance in the balance between bacterial virulence and host resistance.  3 major groups of bacteria based on virulence Primary pathogens (probable agents of infection) Opportunistic pathogens (bacteria isolated from animals with compromised host defense mechanisms considered as agents of the infection Non-pathogenic forms (bacteria that are rarely or never caused a disease. The non-pathogenic nature may change because of the adaptability of bacteria to mount resistance mechanisms).  Genetic and molecular basis for bacterial virulence Plasmid-encoded (regulation of virulence by extra-chromosomal DNA; Example: heat-labile enterotoxin (LTI) of E. coli) Bacteriophage-mediated (integration of the bacteriophage genome into the bacterial chromosome through lysogeny Transposon-encoded (transfer of virulence genes across and among bacteria) Bacterial chromosome-encoded (regulation of virulence by specific genes in the bacterial DNA) (Example: heat-labile toxin (LTII) of E. coli); cholera toxin, Salmonella enterotoxin and Yersinia invasion factors) Bacterial enzyme mediated (NAD+ glycol-hydrolases acting as ADP-ribosyl-transferases for cholera toxin, diphtheria toxin, Pseudomonas exotoxin A and pertussis toxin) Host-mediated basis for bacterial virulence Toxic mediators released by lymphoid cells, macrophages and poly-morphonuclear neutrophils infiltrating the site of infection Cause damage in tissues, allowing bacteria to proliferate in the absence of a cellular response  Intracellular growth of pathogens and enhancement of virulence Multiplication of pathogenic bacteria in tissue fluids of host cells and exert pathogenic effects in those locations(Rickettsia species) Bacterial possession of specialized mechanisms that protect them from the harsh effects of the lysosomal enzymes and shield from humoral antibodies to be eliminated only by a cellular immune response (Rickettsia, Coxiella and Chlamydi; and Salmonella, Shigella, and Yersinia as facultative intracellular pathogens, invading cells when it gives them a selective advantage in the host) Production of phospholipases that dissolve the phagocytic vesicle surrounding pathogens (R. rickettsi) and destroys the phagosomal membrane. Growth preference for the intracellular environment of macrophages (Legionella pneumophila) favorable for blocking lysosomal fusion..  Intracellular growth of pathogens and enhancement of virulence Bacterial preference for low-pH environment within the lysosomal granules (Coxiella burnetti) Resistance to intracellular killing by phagocytic cells (Salmonella and Mycobacterium) Capacity of bacteria to survive and multiply within host cells (Most bacterial pathogens do not invade cells but proliferate instead in the extracellular environment enriched by body fluids) Bacterial adhere to epithelial surfaces, penetrate body tissues and cause disease by secreting potent protein toxins (V. cholerae and Bordetella pertussis); non-invasive bacteria (E. coli and P. aeruginosa) Bacterial spread to tissues after gaining access to the body.  Bacterial infectivity (Virulence Factors) Toxins, surface coats (inhibit phagocytosis) and surface receptors (bind to host cells). Virulence factors allow bacteria to multiply in the host or vector without being killed or expelled by the host defenses Disease often depends on the interaction of virulence factors with the host response (An infection begins when the balance between bacterial pathogenicity and host resistance is disturbed) Some bacteria that are poorly adapted to the host can synthesize virulence factors (tetanus and diphtheria toxin) that are potent and threatens the life of the host. Function of virulence factors invade the host cause disease evade host defenses. Cellular origin of bacterial virulence factors  Functional types of virulence factors 1. Adherence and colonization factors adherence to a mucosal surface as a requirement alimentary tract mucosa mucus from goblet cells and by the peristaltic flow of the gut contents ciliated cells in the respiratory tract sweep mucus and bacteria upward infection is established first by the attaching pathogen and multiplies before the release of mucus from goblet cells Adherence/Attachment mechanisms in bacteria Pili (fimbriae) and colonization factors that recognize and attach the bacteria to cells. V. cholerae, E. coli, Salmonella spp., N. gonorrheae, N. meningitidis and Streptococcus pyogenes. 2. Invasion factors Surface components facilitate the entry of bacterium in mucosa (plasmid and chromosome- mediated. Rickettsia and Chlamydia species (obligate intracellular pathogens) and Shigella  Functional types of virulence factors 3. Capsules and other surface components protect bacteria from opsonization and phagocytosis make bacteria less readily engulfed by phagocytes, scavenger leukocytes and cells of the reticulo-endothelial system Examples: Polysaccharide capsule of D. pneumonia; and D-glutamic acid-containing capsule of B. anthracis surface antigen (Vi antigens) Enable bacteria to survive and multiply inside phagocytic cells Mycobacterium tuberculosis, Brucella abortus, Listeria monocytogenes and Legionella pneumophila 4. Endotoxins lipopolysaccharides (LPS), Lipid A outer membrane of Gram-negative bacteria fever, changes in blood pressure, inflammation, lethal shock and many other toxic events.  Biologic activity of endotoxin Sepsis and lethal shock and other toxic effects like: pyrogenicity leukopenia followed by leukocytosis complement activation Low blood pressure mitogenicity induction of prostaglandin synthesis hypothermia Limulus lysate test or the rabbit pyrogenicity test. 5. Exotoxins potent protein poisons/toxins released from viable bacteria. heat-labile or heat-stable peptides Gram-positive bacteria (Some studies described exotoxin in a few Gram- negative bacteria) Site of action is localized and confined to particular cell types or cell receptors Examples: Tetanus toxin in internuncial (neck region) neurons. Several categories of exotoxins 1. Neurotoxins (botulinum toxin formed by C. botulinum) act on motor neurons, prevents the release of acetylcholine at the myoneural junctions thereby preventing muscle excitation and producing flaccid paralysis. 2. Cytotoxins (wide array of host cell specificities and toxic manifestations) Example: diphtheria cytotoxin of Corynebacterium diphtheriae 3. Enterotoxins stimulate hypersecretion of water and electrolytes from the intestinal epithelium to produce watery diarrhea, disturb normal smooth muscle contraction, cause abdominal cramping and decrease transit time for water absorption in the intestines. shiga-like enterotoxin from and cholera toxin of E. coli ) 6. Siderophores iron-binding factors that allow bacteria to compete with the host for iron which is bound to hemoglobin, transferrin and lactoferrin. iron acquisition is facilitated by transferrin-binding outer membrane proteins of some bacteria To capture iron from the host In the absence of iron, transcription of the genes coding for the enzymes that synthesize siderophores is triggered and a set of surface protein receptors that recognize siderophores carry the bound iron. Neisserira spp.  Extracellular enzymes and activators a. Alpha toxins ▪ hydrolyze lecithinase and possess hemolytic and necrotic effects ▪ produced by Clostridium perfringens b. Hyaluronidase ▪ hydrolyzes the ground substance (hyluronic acid) present in connective tissues a spreading factor ▪ produced by Staphylococcus and Streptococcus c. Coagulase ▪ increases the rate of plasma clotting and provides mechanical barrier to phagocytes ▪ produced by Staphylococcus d. Streptokinase ▪ prevents walling-off of infecting bacteria ▪ produced by Streptococcus e. Hemolysin ▪ causes lysis of RBC and WBC ▪ Examples include Streptolysins O and S f. Proteinases ▪ hydrolyzes muscle collagen and proteins and causes dissolution of tissues ▪ produced by Clostridium perfringens g. Cord factor ▪ isolated and identified as a lipid material at the cell surface of Mycobacterium tuberculosis h. Extracellular deoxyribonucleases of Streptococci i. Aggressins j. Invasins k. Necrotizing toxins l. Leukocidins m. Allergic factors Thank you - END-