Bacterial Pathogenicity Flashcards
What is bacterial pathogenicity
Mechanisms by which bacteria cause disease
Vast majority of bacteria are…
Non-pathogenic
2 broad groups of successful pathogens
Opportunistic pathogens and primary pathogens;
Both groups have virulence factors that contribute to their ability to cause disease;
Opportunistic pathogens
Only cause disease or serious disease in immunocompromised individuals
Primary pathogens
Capable of causing disease in individuals with a fully functioning immune system
Virulence factors/ determinants are..
Contribute to ability to cause disease;
Rarely is a possession of single virulence - multi factorial;
Bacterial surface components and composition of the bacterial surface and its interactions with the immune system;
Stages in disease progression
Colonisation; Invasion; Avoidance of host cell defences; Tissue damage; Transmission;
Colonisation
Establishment of a stable population of bacteria in the host following entry into body;
Bacterial entry into host is effected by the respiratory tract, gastrointestinal tract and skin;
Source of infection varies - from infected individual, environmental sources, normal human flora;
Involves adherence to mucosal surfaces to avoid being washed away due to flushing action of urine in bladder, saliva in mouth and peristalsis in gastrointestinal tract;
Colonisation resistance
Norma human flora may prevent colonisation by potential pathogens
2 processes in colonisation
Adherence and nutrient acquisition
Adherence in colonisation
1st stage - association - involves non-specific forces (charge and hydrophobicity) - weak and reversible;
2nd stage - adherence - specific binding between bacterial adhesins and host receptors - strong interaction, irreversible;
Bacterial surface adhesins that bind to receptors on mammalian cell surfaces or glycocalyx;
Bacterial adhesins - polysaccharides, fimbriae (pilli), flagella, proteins;
Adhesion to mammalian cell surface triggers intracellular events that result in pathology;
Bacteria can also adhere to biomaterials - replacement heart valves, catheters and grow as biofilm. These bacteria may contribute to chronic infection and be more resistant to antibiotic therapy.
Bacterial pathogens
Ubiquitous;
Vast majority are harmless;
Host immune system very efficient at preventing most bacteria from causing disease;
Infection
Persistence without necessarily causing tissue damage
Disease
Overt damage to host
Host receptors include
Blood group antigens and extracellular matrix proteins (fibronectin, collagen)
Nutrient acquisition in colonisation
Bacteria require nutrients to grow in Vivo to maintain population - iron is particularly important;
Levels of free iron in tissue are very Low - most iron is intracellular and the remainder is tightly bound to transferrin, lactoferrin or other iron-binding glycoproteins;
Bacteria have evolved efficient mechanisms to acquire iron in Vivo;
Mechanisms of bacteria to acquire iron in Vivo
2 main:
Siderophores and direct binding of iron transport proteins (transferrin, lactoferrin)
Invasion
Bacteria are able to penetrate into, through, in between cells;
May aid in survival and spread to other body sites;
Adhesion to specific receptors is the first stage of invasion - adhesins called invasins;
Bacteria can invade epithelial cells (shigella) or invade phagocytic cells ( macrophages - salmonella, mycobacteria);
Host defences
Immune system effective at eliminating non-pathogenic bacteria;
Complement kills many gram negative bacteria;
Complement and antibodies oposonize bacteria, promoting phagocytosis and killing polymorphonuclear leukocytes (PMNs) and macrophages;
Cytokines module both antibody and phagocytic responses;
Avoidance of host defenses
Bacterial pathogens have evolved numerous mechanisms to avoid host immune system
Avoidance of complement
Gram negative bacteria causing sepsis is complement resistant and can therefore survive and grow in the bloodstream;
Resistance is due to LPS (lipopolysaccharides)on the bacterial surface;
Polysaccharides side chains of LPS sterically hinder access of activated complement components to the bacterial membrane;
Capsule may also interfere with complement binding (eg. E. coli);
Surface proteins inhibit binding of complement to bacterial surface (streptococcus pyogenes);
Staph. Aureus produces factors that interfere with complement activation;
Avoidance of antibody
Bacterial capsules prevent antibody binding and are weakly antigenic preventing opsonization and phagocytosis;
Many different capsular types may be produced;
Antigenic variation used to avoid antibiotic binding;
Avoidance of phagocytes
Bacteria produce toxins that kill phagocytes or inhibit migration to sites of infection;
Inherent physical properties of some bacterial pastels inhibit phagocytosis;
Some bacteria inhibit pathways involved in intracellular killing with phagocytes;
Modulation of cytokine responses
Bacteria can alter normal cytokine responses in favour of bacterial survival
Tissue damage (3 ways)
Direct effects of bacterial toxins;
Indirect effects of bacterial toxins;
Induction of autoimmune responses;
2 types of bacterial toxins
Exotoxins - actions selective for specific biochemical targets (eg. Protein synthesis);
Endotoxins (LPS) - activates many biochemical pathways - effects mediated by triggering of cytokine release from mammalian cells; cytokines released include TNF -alpha;
Exotoxins properties
Made by gram positive and negative; Protein; Cytoplasmic; Secreted by living bacteria; Usually heat labile; Toxoids available; Potentially lethal
Endotoxin properties
Made by gram positive; Lipopolysaccharide; Outer membrane; Released on cell lysis; Usually heat stable; No toxoids; Lethal at high conc.
Exotoxin classification
Classier based on specific mode of action (membrane acting, membrane damaging);
Tetanus toxin - interferes with synapse function;
Diphtheria toxin - inhibits mammalian protein synthesis;
