1. FACTORS OF PATHOGENICITY Lecture for 2nd-year students
Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno
Miroslav Votava
FACTORS OF PATHOGENICITY
AND VIRULENCE – II
Lecture for 2nd-year students
April 14th, 2008

2. Three elements of pathogenicity and virulence – reiteration
1. Communicability (transmissibility) = ability to be transmitted between hosts
2. Invasiveness = ability to:
- enter the host ability to
- multiply in it = overcome
- spread through it the defence
3. Toxicity = ability to do harm to the host

3. Transmissibility – reiteration
It depends on
the way of transmission – especially on
the way, in which microbes leave the body the amount of excreted microbes what is the portal of entry into other host
the microbe tenacity – the degree of resistance to the external environment
the minimum infectious dose – the number of microbes required for the start of infection
the behaviour of host – the abuse of host‘s defensive reflexes for the transmission

4. Invasiveness – reiteration
Entry: most often through mucosae
adherence to epithelium by means of fimbriae or other adhesins
penetration through epithelium
direct one
forced phagocytosis
Multiplication in vivo:
intracellular multiplication
better (intracellular parasites)
extracellular multiplication – obstructed by
shortage of free Fe
antibacterial substances
high temperature

5. Spread through the body – reiteration
Localized infections (common cold, infectious diarrhoea, gonorrhoea)
Systemic infections (influenza, meningitis)
Generalized infections (measles, typhoid fever, exceptionally: localized and systemic infections)
Way of spreading:
by means of lymph
by means of blood
per continuitatem
along nerves
(later in the lecture on the pathogenesis of infection)

6. Ability to overcome the defence – A
A) Ability to overcome the innate immunity:
To resist complement to inhibit complement activation to protect one‘s own surface
To resist phagocytosis not to allow being engulfed to survive inside the phagocyte
To interfere with the cytokine function

7. Ability to resist complement
Inhibition of complement activation
capsule – shielding surface molecules (meningococci, pneumococci) activation inhibitors (gonococci – addition of sialic acid to terminal saccharides, many viruses, E. coli and S. pyogenes – production of regulation factor H, S. pyogenes and P. aeruginosa – enzymes splitting C3b a C5a)
Protection of the surface (salmonellae and E. coli in S phase, flagella of motile bacteria)
Ability to resist complement → seroresistance

8. Ability to resist phagocytosis – I
1. Not to allow being engulfed
inhibitors of chemotaxis (bordetellae, vaginal anaerobes, pseudomonads)
leucocidins and lecithinase (staphylococci, streptococci, pseudomonads, clostridia)
injecting Yop (yersiniae)
formation of capsule (most important!)
agents of meningitis and pneumonia (N. meningitidis, H. influenzae, E. coli, S. pneumoniae, K. pneumoniae)

9. Ability to resist phagocytosis – II
2. To survive inside the phagocyte
blockade of phagolysosome formation (Chlamydia, Mycobacterium, Legionella, Toxoplasma)
escape from phagosome (Rickettsia, Shigella, Listeria, Leishmania, Trypanosoma)
production of antioxidants
(staphylococci, gonococci, meningococci)
marked tenacity
(Coxiella, Ehrlichia)

10. Ability to overcome the defence – B
B) Ability to overcome the acquired immunity:
Always an attempt to avoid antibodies or immune lymphocytes
to reproduce quickly (respiratory viruses, diarrhoeal agents, malarial plasmodia)
attempt to deceive immune system
to hide itself
to change one‘s own antigens
to induce tolerance
attempt to suppress immune reaction

11. Ability to deceive the immune system – I
To hide itself in ganglions (HSV, VZV) on intracellular membranes (HIV, adenov.) in infectious focuses (M. tbc, echinococci) in privileged sites (agents of mucosal infections, T. gondii in eye, retroviruses in cellular genome)
2. To induce the immune tolerance
(CMV, rubella v., leishmaniae, cryptococci, maybe even HIV)

12. Ability to deceive the immune system – II
3. To change antigens of one‘s own
antigenic mimicry (S. pyogenes, T. pallidum, M. pneumoniae)
antigenic camouflage (schistosomes – blood proteins, staphylococci – protein A, streptococci – protein G, CMV – βmG)
antigenic variability (trypanosomes, borreliae, gonococci, influenza virus)

13. Ability to deceive the immune system – III
4. To suppress immune reaction
invasion into the immune system (HIV, measles virus) interference in cytokine formation (M. leprae, protozoa) production of superantigens (staphylococci, streptococci) production of proteases (meningococci, gonococci, haemophili, pneumococci) binding Fc fragment of IgG (staphylococci, streptococci, HSV)
? (influenza virus, HBV, EBV)

14. Toxicity – I Damage by direct effect of infectious agent
Cellular death lysis by toxins, viruses, immune lymphocytes apoptosis (HSV, shigellae)
Metabolic injury – influence of exotoxins
Mechanical causes (schistosomal eggs, P. jirovecii, pseudomembranes in diphtheria)
The most frequent cause of death → septic shock triggered by endotoxins G – : lipopolysaccharide G + : teichoic acid + peptidoglycan

15. Bacterial exotoxins
Spreading factors (hyase, DNase, elastase, collagenase)
Cytolysins (lecithinase, sfingomyelinase, hemolysins)
Inhibitors of proteosynthesis (diphtheria toxin)
Pharmacologically effective toxins (choleragen, E. coli thermolabile enterotoxin, pertussis toxin)
Neurotoxins (tetanotoxin, botulotoxin)
Superantigens (staphylococcal enterotoxin and exfoliatin, streptococcal pyrogenic toxin)

16. Toxicity – II Damage as a result of defence reactions
a) Injuries caused by inflammatory reaction: calor, rubor, tumor, dolor, functio laesa = typical markers of inflammation = symptoms of disease
edema: encephalitis, epiglottitis inflammatory infiltrate: pneumonia suppuration: blennorrhoea neonatorum formation of connective tissue: scarring

17. Toxicity – III Injury as a result of defence reactions
b) Injuries caused by specific immune reaction (immunopathological consequences of hypersensitivity)
1st type: (IgE, anaphylaxis) helminthoses
2nd type: (cytotoxicity) hepatitis B, febris rheumat.
3rd type: (immunocomplexes) farmers lungs, poststreptococcal nephritis, systemic reactions during sepsis
4th type: (late, cellular) tbc, lepra, syphilis, actinomycosis, rash in measles

18. Recommended reading material
Paul de Kruif: Microbe Hunters Paul de Kruif: Men against Death Axel Munthe: The Story of San Michele Sinclair Lewis: Arrowsmith André Maurois: La vie de Sir Alexander Fleming Hans Zinsser: Rats, Lice, and History Michael Crichton: Andromeda Strain Albert Camus: Peste Victor Heisser: An American Doctor Odyssey