lecture 4 - bacterial pathogenesis Flashcards
Where do bacteria live in the body?
mouth, skin, respiratory tract, gastrointestinal tract, urogenital tract
How are normal flora/ indigenous microbiota beneficial/harmless to the host?
Normal flora includes >200 species.
protection against colonization by harmful bacteria;
production of antimicrobial compounds;
synthesis of vitamins
stimulation of the production of natural antibodies
How can members of the normal flora turn from harmless to harmful?
in immunocompromised hosts (HIV, cancer patients)
when they move from their site of colonization to adjacent areas of normally sterile tissues, often as a result of surgery or intestinal perforation.
What makes a pathogen?
A microorganism that is able to cause disease in an animal, plant or insect.
More than 100 bacterial species cause disease in humans.
Two mechanisms underpinning pathogenesis are:
Invasiveness
Toxigenicity
These two factors determine the virulence (capacity to cause disease) of a pathogen.
What is invasiveness?
The ability of a pathogen to invade the body, spread into it and to establish an infection.
It involves mechanisms for:
colonization (adherence and initial proliferation)
production of extracellular substances which facilitate invasion (invasins)
evasion of the host defences
What routes of entry correspond to what bacterial diseases?
Inhalation of contaminated air: respiratory diseases
Ingestion of contaminated food or water: intestinal diseases
Contact with another infected host: sexually transmitted diseases
Bite by an infected organism: vector-borne diseases
How does colonisation take place?
Pathogenic bacteria gain access to our body through a wound or getting inside us through the mouth, nose etc. and then to infect the host they need to stick to the tissue in a rather substantial way, so that they are not swept away. Bacteria adhere to the epithelial cells of the mucous membranes of the respiratory, intestinal or urogenital tract and they do this through specific interactions between molecules on their surface and molecules on the host cells. Pili are structures used to adhere to epithelial cells: they are hair-like appendages made out of subunits of a protein called pilin. However, the protein at the very tip of the pilus is not pilin, but another protein that bind to specific receptors on the surface of epithelial cells. This strategy allows the binding to different receptors and so different types of cell.
What is toxigenicity?
The ability to damage the host by producing toxic chemicals. (exotoxins and endotoxins)
What are exotoxins?
Proteins that are secreted by the pathogen. Usually enzymes. Destroy cellular structures. Classified as: - cytotoxins - neurotoxins - enterotoxins neurotoxins target the nervous system, enterotoxins the intestinal tract and cytotoxins attack multiple tissues.
What is the structure of an exotoxin and how do they work?
Many exotoxins consist of two subunits, subunit A and subunit B.
Subunit A is the toxin, whereas subunit B has a role in transporting the toxin into the target cell.
Some AB toxins bind to receptor molecules on the host cell membrane and the B subunit induces the formation of a pore in the cell membrane, through which the A subunit is transferred inside the cell, while the B subunit remains outside.
The other mechanism for entry involves endocytosis: the AB subunits are taken, internalized in the cell through a membrane- formed vesicle, called endosome.
Hydrogen ions enter the endosome lowering the pH and causing the A and B subunits to dissociate.
Then the A subunit is transferred into the cytoplasm, where it will reach its target, whereas the B subunit remains in the endosome and it is recycled to the surface of the cell.
What are endotoxins?
Lipopolysaccharides of the cell envelope of Gram- negative bacteria
Attached to the bacterial cell
Small amounts of LPS are continually released by growing bacterial cells, but much more is released if the bacterial cells lyse (for example due to antibiotic killing). Endotoxins are taken up by cells of the immune system called phagocytes. As a result, the phagocytes release cytokines, soluble proteins, that act as endogenous pyrogens, proteins that affect the temperature-controlling center of the brain, causing fever.
What are antibiotics?
Chemicals that kill or inhibit the growth of microorganisms
Used to treat microbial infections.
Some are natural products of microbes, but many are now chemically synthesized.
- Natural - Semi synthetic - Synthetic
How do antibiotics work?
Work by interfering with a bacteria-specific biological process:
- cell wall synthesis - cell membrane structure - protein synthesis - nucleic acid synthesis
How does drug resistance develop?
Drug resistance is acquired by chromosomal mutation or acquisition of a plasmid or fragment of DNA carrying a gene encoding for the resistance from a resistant bacterium
With time, they can become resistant to multiple antibiotics.
