Baedah Madjid Depart. of Microbiology, Medical Faculty, Hasanuddin University.

2006

Student must able to explain about pathomechanisms of infection Student must know how to explain about:
the steps of bacterial pathogenesis the microbial factors involved in the

onset and spread of microbial infection.

the strategy for bacterial survival

the factors affect the outcome of infection

 Definition : terms connected

Transmission Infection

Steps of bacterial pathogenesis

Factors affect the outcomes of infection

Summary

 Normal Flora: microorganisms that are frequently

found in various body sites in normal, healthy individuals.

Pathogens :
- in medicine: pathogen is any microorganisms capable of causing diseases

- Microbiology: being pathogen microbe must posses

virulence factors (microbial pathogenicity)

Pathogen opportunistic
Non-pathogen bacteria pathogen on susceptible host

 Pathogenesis = pathogeny:
the organization & development of infection

Pathogenicity: the quality or state or being pathogenic;

degree of pathogenic capacity.

Invasion: the penetration of the hosts body by

microorganisms

1. Encounter port the entry: epithel cell 2. Attachment to host cells = adherence 3. Invasion 4. Multiplication 5. Dissemination

Site of Microbial Contamination or

Port the Entry

Pili = fimbriae

Non- fibrillae

Bacteria :
adhesin

Host epithel:
receptor

- Pilli or fibrillae

- Afibrial adhesins
* Lectin (carbohydrate-binding-protein)

* Lipoteichoic acid * Fibronectin-binding-protein * M-protein * Outer membrane protein * Polysaccharide capsule

1. Encounter 2. Attachment to host cells

Multiply

3. Invasion

Colonization Carrier state

(pathogen)

1. Encounter port the entry: epithel cell 2. Attachment to host cells 3. Invasion

The penetration of the body of a host by a microorganism (Merriam Websters Medical

Desk Dictionary)

 Getting into cells multiplication Resisting the degradative enzymes

The advantages for intracellular (epithelia or PMN cells) pathogens : . Environment potentially rich in nutrients . No competing microorganisms . No immune system

Mechanisms
Survival the phagocyte & Complement attack Inhibition of chemotaxis Killing by phagocyte before ingestion Avoiding ingestion (Phagocytose)

Examples
C5a peptidase by Str. pyogenes -toxin and leukocidin by Staph. aureus
Bacterial

capsule (Streptococcus pneumoniae.) LPS O Ag in Gr-neg rods Coating with IgA Antibodies (Neisseria meningitidis) M. protein (Streptococcus pyogenes)

Mechanisms
Surviving within phagocytes

Examples
Inhibition of phagosome fusion (Chlamydia trachomatis) Escape phagolysosome (Listeria monocytogenes) Resistance to lysosomal product (Salmonella typhimurium) Inhibition of early host gene expression (M. tuberculose) Shift and drift in influenza A virus Prenatal infections Depletion of CD4+ T cells by HIV IgA protease by H. influenzae Latent infection in dorsal root ganglia (Herpes simplex virus)

Antigenic variation Tolerance Immunosuppression -Destroying lymphocytes - Proteolysis of antibodies Presence in inaccessible sites

1. Encounter entry 2. Attachment to host cells 3. Invasion 4. Multiplication

Metabolite excretion Tissue Damage

Primary lesion

MECHANISMS OF CELL AND TISSUE DAMAGE BY MICROORGANISMS Mechanism

Direct damage by microorganisms
Production of toxins

Examples
See next table

Production of enzymes Proteases, coagulase, DNAse, Apoptosis HIV (CD4+ T cells), Shigella flexneri (macrophage) Virus induced cytopathic effects: cell lysis formation of syncytium Inclusion bodies: - intracytoplasmic - Nuclear Transformation

Cytomegalovirus Respiratory syncytial virus Rabies Herpes viruses Human papilloma-viruses type 16

MECHANISMS OF CELL AND TISSUE DAMAGE BY MICROORGANISMS Mechanism

Damage via the host immune response

Examples

Cytotoxic T cells & Production of measles natural killer rash lymphocytes Autoimmunity Acute Rheumatic fever Immediate hypersensitivity Cytotoxic hypersensitivity Immune complexes Delayed type hypersensitivity Rashes associated with helminthic infection Cell necrosis induced by hepatitis B Glomerulonephritis in malaria Tuberculosis granuloma

EXAMPLES OF BACTERIAL TOXINS

Toxin type Endotoxin (LPS, lipid A) Membrane disrupting toxins Sources
Gr- Bacteria

Toxin
Endotoxin

Target
Macrophage, Neutrophils, lymphocytes, Plasma components

Effects
Septic shock

Staph. aureus

A-B type toxins

Many cells types L.monocytoges Listeriolysin Many cells types Cl. perfringens Perfringoly-sin- Many cells O types Cl. tetani Tetano-spasminSynaptic transmission C. diphtheriae Diphtheria Many cells toxin types Vibrio cholerae Cholera toxin Intestinal cells Str. pyogenes Staph. aureus Streptococcal pyogenic exotoxin Toxic shock T. cells, macrophage T. cells,

-toxin

Tissue necrosis Escape from the phagosome Gas gangrene Spastic paralysis Paralysis Profuse watery diarrhea Fever, eruption, toxic-shock like syndrome Toxic shock

Superantigen

NO.
1. 2. 3. 4. 5. 6. 7. 8. 9.

V. FACTORS
Pilli Capsule Protein M Outer membrane protein Toxin Hyaluronidase IgA protease DNAse Coagulase

USED FOR
Attachment Avoiding ingestion Attachment Attachment See Toxin tables Spreading Breaking Surface IgA Destroying hosts cell Avoiding ingestion

 Endotoxin

- = Lypopolysacchride (LPS) wall of

negative-gram bacteria - Septic shock

Exotoxin
- Metabolite excretion protein - Effect: Lyses Neurotoxin Enterotoxin

1. Encounter entry 2. Attachment to host cells 3. Invasion 4. Multiplication 5. Dissemination Indirectly

-hematogenously --lymphatogenously

Directly

Bacteria can be eliminated by:

1. Natural host defense:
- Lysozyme and other enzyemes - Acid - Complement

2. Acquired host defense:

- Antibodies

3. Antibiotics therapy

Symptomatic Asymptomatic disease = sub-clinic diseases

Depend on: 1. The organisms ability to breach host barrier & to
evade destruction by innate local and tissue host defences.

2. The organisms biochemical tactics to replicate, to spread, to

establish infection, and to cause disease. 3. The microbes ability to transmit to a new susceptible host. 4. The hosts innate and adaptive immunologic ability to control and eliminate the invading microbes.

DOSE OF MICROORGANISMS REQUIRED TO PRODUCE INFECTION IN HUMAN VOLUNTERS MICROBE Rhinovirus Salmonella typhi Shigella spp. Vibrio cholerae Mycobacterium tuberculosis ROUTE Pharynx Oral Oral Oral Inhalation
DISEASE-PRODUCING DOSE

200 105 10 - 1000 108 1 - 10

1. Pathogen:
- Posses virulence factors - Opportunistic pathogen: NF or colonization of pathogens on carrier Environment bacteria

2. Outcomes of infection is depend on:

- Pathogenicity of bacteria - Dose of contamination - Host defense mechanisms

FURTHER READING

Brooks, GF., Butel, JS., Morse, SA. Jawetz, melnick, & Adelbergs Medical Microbiology. 23rd Edition, International Edition, McGraw-Hill, Singapore, 2004. Cohen, J. et al. Infectious Diseases, 2nd Edition, Mosby, Sydney, 2004. Joklik, WK., Willett, HP., Amos, DB., Wifert, CM. Zinsser Microbiology, 20th edition, Appleton & Lange, Connecticut1992. Mims, C., et al. Medical Microbiology, 3rd Edition, Mosby, Sydney, 2004 Ryan, KJ., Ray, CG. Sherris Medical Microbiology , an Introduction to Infectious Diseases, McGraw-Hill, Singapore, 2004. Virella G. Microbiology and Infectious Diseases, 3rd Edition, Edited., Williams and Wilkins, Baltimore, 1997.