Bacterial Pathogenicity

Question 1

What is bacterial pathogenicity

Answer 1

Mechanisms by which bacteria cause disease

Question 2

Vast majority of bacteria are…

Answer 2

Non-pathogenic

Question 3

2 broad groups of successful pathogens

Answer 3

Opportunistic pathogens and primary pathogens;

Both groups have virulence factors that contribute to their ability to cause disease;

Question 4

Opportunistic pathogens

Answer 4

Only cause disease or serious disease in immunocompromised individuals

Question 5

Primary pathogens

Answer 5

Capable of causing disease in individuals with a fully functioning immune system

Question 6

Virulence factors/ determinants are..

Answer 6

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;

Question 7

Stages in disease progression

Answer 7

Colonisation;
Invasion;
Avoidance of host cell defences;
Tissue damage;
Transmission;

Question 8

Colonisation

Answer 8

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;

Question 9

Colonisation resistance

Answer 9

Norma human flora may prevent colonisation by potential pathogens

Question 10

2 processes in colonisation

Answer 10

Adherence and nutrient acquisition

Question 11

Adherence in colonisation

Answer 11

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.

Question 12

Bacterial pathogens

Answer 12

Ubiquitous;
Vast majority are harmless;
Host immune system very efficient at preventing most bacteria from causing disease;

Question 13

Infection

Answer 13

Persistence without necessarily causing tissue damage

Question 14

Disease

Answer 14

Overt damage to host

Question 15

Host receptors include

Answer 15

Blood group antigens and extracellular matrix proteins (fibronectin, collagen)

Question 16

Nutrient acquisition in colonisation

Answer 16

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;

Question 17

Mechanisms of bacteria to acquire iron in Vivo

Answer 17

2 main:

Siderophores and direct binding of iron transport proteins (transferrin, lactoferrin)

Question 18

Invasion

Answer 18

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);

Question 19

Host defences

Answer 19

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;

Question 20

Avoidance of host defenses

Answer 20

Bacterial pathogens have evolved numerous mechanisms to avoid host immune system

Question 21

Avoidance of complement

Answer 21

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;

Question 22

Avoidance of antibody

Answer 22

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;

Question 23

Avoidance of phagocytes

Answer 23

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;

Question 24

Modulation of cytokine responses

Answer 24

Bacteria can alter normal cytokine responses in favour of bacterial survival

Question 25

Tissue damage (3 ways)

Answer 25

Direct effects of bacterial toxins;
Indirect effects of bacterial toxins;
Induction of autoimmune responses;

Question 26

2 types of bacterial toxins

Answer 26

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;

Question 27

Exotoxins properties

Answer 27

Made by gram positive and negative;
Protein;
Cytoplasmic;
Secreted by living bacteria;
Usually heat labile;
Toxoids available;
Potentially lethal

Question 28

Endotoxin properties

Answer 28

Made by gram positive;
Lipopolysaccharide;
Outer membrane;
Released on cell lysis;
Usually heat stable;
No toxoids;
Lethal at high conc.

Question 29

Exotoxin classification

Answer 29

Classier based on specific mode of action (membrane acting, membrane damaging);
Tetanus toxin - interferes with synapse function;
Diphtheria toxin - inhibits mammalian protein synthesis;