MEDICAL MICROBIOLOGY

LECTURE 4. PATHOGENICITY AND PATHOGENESIS OF INFECTIOUS DISEASE. MECHANISMS AND FACTORS

Omirbekova Anel A., PhD, Associated Professor

HOW MICROORGANISMS ENTER A HOST

Pathogenicity: Ability of a pathogen to cause disease by overcoming the host defenses

Virulence: Degree of pathogenicity.

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Attachment is step 1:

Bacteria use ___________

___________

Viruses use ___________

To cause disease, most pathogens must gain access to the host, adhere to host tissues, penetrate or evade host defenses, and damage the host tissues.

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Pathogens can gain entrance to the human body and other hosts through several avenues, which are called portals of entry.

(Preferred) Portals of Entry

Mucous membranes

• Conjunctiva
• Respiratory tract: Droplet inhalation of moisture and dust particles. Most common portal of entry.
• GI tract: food, water, contaminated fingers
• Genitourinary tract

Skin

• Impenetrable for most microorganisms; can enter through hair follicles and sweat ducts.

Parenteral Route

• Trauma (S. aureus, C. tetani)
• Arthropods (Y. pestis)
• Injections

Numbers of Invading Microbes

If only a few microbes enter the body, they will probably be overcome by the host’s defenses. However, if large numbers of microbes gain entry, the stage is probably set for disease. The likelihood of disease increases as the number of pathogens increases.

The amount of a pathogen that is required to establish an infection  is called the “infectious dose.” If a person were to be exposed to exactly one copy of a SARS-CoV-2 virus or a single Bartonella species bacterium, it is unlikely they would become infected. The body’s innate immune system (the immune system that does not require identifying specific pathogens) has several different layers of activity that would neutralize that one viral or bacterial organism.

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Numbers of Invading Microbes

Clinical and Epidemiologic Principles of Anthrax at http://www.cdc.gov/ncidod/EID/vol5no4/cieslak.htm

ID₅₀: Infectious dose for 50% of the test population

LD₅₀: Lethal dose (of a toxin) for 50% of the test population

Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following:

• colonization of a niche in the host (this includes movement towards and attachment to host cells)
• immunoevasion, evasion of the host's immune response
• immunosuppressionimmunosuppression, inhibition of the host's immune response (this includes leukocidin-mediated cell death)
• entry into and exit out of cells (if the pathogen is an intracellular one)
• obtain nutrition from the host

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ADHERENCE

Adhesins: surface �projections on pathogen, mostly made of glycoproteins or lipoproteins. �Adhere to complementary�receptors on the host cells. �Adhesins can be part of:

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• Glycocalyx: e.g.Streptococcus mutans
• Fimbriae (also pili and flagella): e.g.E. coli

Host cell receptors are most commonly sugars (e.g. mannose for E. coli

Biofilms provide attachment and resistance to antimicrobial agents.

OVERCOMING HOST DEFENSES

• Capsules: inhibition or prevention of _____________
• Cell Wall Proteins: e.g. M protein of S. pyogenes
• Antigenic Variation: �Avoidance of IS, e.g.�Trypanosoma�Neisseria
• Penetration into the Host Cell Cytoskeleton: Salmonella and E. coli produce invasins, proteins that cause the actin of the host cell’s cytoskeleton to form a basket that carries the bacteria into the cell.

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PENETRATION INTO THE HOST CELL CYTOSKELETON

• Invasins
• Salmonella alters host actin to enter a host cell
• Use actin to move from one cell to the next
• Listeria

ENZYMES

Coagulase: Blood clot formation. Protection from phagocytosis (virulent S. aureus)

Kinase: blood clot dissolve (e.g.: streptokinase)

Hyaluronidase: (Spreading factor) Digestion of “intercellular cement” ⇒ tissue penetration

Collagenase: Collagen hydrolysis

IgA protease: IgA destruction

Enzymes Used for Penetration

How Pathogens Damage Host Cells

1. Use host’s nutrients; e.g.: Iron
2. Cause direct damage
3. Produce toxins
4. Induce hypersensitivity � reaction

Copyright © 2010 Pearson Education, Inc.

Learning Objectives

Toxins

Exotoxins: proteins (Gram- and + bacteria can produce)

Endotoxins: Gram- bacteria only. LPS, Lipid A part ⇒ released upon cell death. Symptoms due to vigorous inflammation. Massive release ⇒ endotoxic shock

Foundation Fig 15.4

ANIMATION Virulence Factors: Exotoxins

Exotoxins Summary

TOXIN EXAMPLES

Which is the least potent toxin?

1. Botulinum
2. Shiga
3. Staph

Type of Exotoxins:��A-B Exotoxins

Fig 15.5

Fig 15.5

MEMBRANE-DISRUPTING TOXINS

Lyse host’s cells by

• Making protein channels into the plasma membrane, e.g. S. aureus
• Disrupting phospholipid bilayer, e.g. C. perfringens

Examples:

Leukocidin: PMN and MΦ destruction

Hemolysin (e.g.: Streptolysin) : RBCs lysis ⇒ get at?

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Representative Examples of Exotoxins

ENDOTOXINS

• Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins.
• Endotoxins cause fever (by inducing the release of interleukin-1) and shock (because of a TNF-induced decrease in blood pressure).
• TNF release also allows bacteria to cross BBB.
• The LAL assay (Limulus amoebocyte lysate) is used to detect endotoxins in drugs and on medical devices.

Fig 15.6

ENDOTOXIN SUMMARY