LUCA = last universal common ancestor, bacteria – archaea –
eukarya
Archaea: contains many microorganisms which grown under
extreme conditions, not pathogenic
Bacteria and eukarya (yeast/molds, fungi): majority of the
pathogenic and spoilage organisms.
Prokaryotic (bacteria and archaea) vs eukaryotic (eukarya) cells
All cells have:
- Permeability barrier, a cytoplasmic membrane to separate the inside of the cell from the
outside
- Ribosomes, responsible for protein synthesis
- A DNA genome, the complement of all genes in a cell. In prokaryotic cells closed circular
chromosomes and a nucleoid are present. In eukaryotic cells, there are linear molecules
within the nucleus.
Some cells have a cell wall, which lends structural strength to the cell.
Activities of the cells:
All cells show some form of metabolism, namely cell growth and division, but also evolution. Some
cells show differentiation, communication, gene exchange and motility.
Microorganisms:
Bacteria:
- Prokaryotic cell structure, with undifferentiated single cells with a length ranging form 0.2 –
10 micrometre
- Lack of nucleus
- Can adapt themselves to a large variety of
environments, like anaerobic/aerobic
- Have capacity to grow extremely fast.
Human bacterial infections are caused by strict pathogenic species, or by opportunistic pathogens.
There is a large variety of infections, e.g. food poisoning, pneumonia, skin infections, urinary tract
infection, throat and mouth infection, meningitis, eye infection. The amount of cells needed for an
infection varies: e.g. 10 cells of shigella dysentriae to provoke dysentery, but at least 1000 cells of
Vibrio cholera to provoke cholera.
Bacterial endospores or sporulation:
, - Highly differentiated cells that are extremely resistant to heat, harsh chemicals and radiation
- Survival structures
- Enable the organism to endure unfavourable growth conditions
- Dormant state of the cell
Mollicutes or mycoplasmas:
- Smallest free-living prokaryotic organisms
- Lack a cell wall
- Relatively resistant to osmotic lysis due to sterols in the cell membrane
- Widespread in nature
- Most that infect humans are extracellular parasites (mycoplasma pneumonia, mycoplasma
genitalium)
Fungi: molds, mushrooms and yeasts
- Inhabit soil or dead plant matter, multicellular
- The difference between molds and yeast is not always clear. Molds are obligate aerobic,
grow on the surface or the uppermost layers of a substrate. Yeasts are typically unicellular
organisms, budding.
- Some fungi are pathogenic to humans, e.g. trichophyton sp. or candida sp, or produce toxic
substances like aspergillus flavus
- Cause contamination and spoilage
Viruses:
- A non-cellular genetic element which is dependent in a suitable host cell for its multiplication
- Size ranges form 20-300 nm
- Are not living organisms, since they lack independent metabolism
- Composed of a core of genetic material (and a protein coat or capsid), either in the form of
DNA or RNA
Prions:
- Proteinaceous infectious particle
- Unique type of infectious agent
- Prion disorders: neurodegenerative disorders like scrapie, kuru, bovine spongiform
encephalopathy and Creutzfeldt-Jacob disease
- Long incubation period
- Fatal once clinical symptoms have appeared
- Infectious prions are generated in the brain
Biological contamination: raw materials used for pharmaceutical preparations
- European pharmacopoeia (endotoxins, LPS)
- Virus: use of a virus retentive filter, verify by performing in vivo testes or in vitro tests such as
PCR
- Prions: TSE free: purchasing materials from non-animal origin or from non-TSE relevant
animals
- If purchased from TSE-relevant animal species a certificate is needed
Biological contamination: the impact
- Direct hazard to patient
- Whether a contaminated product will trigger infection or disease depends on number of
microorganisms (CFU per g or ml), ability to grow and metabolize, properties of the particular
strains, immunocompetence of patient (diseases or suppressive), administration route
Biological contamination: natural barrier
, - Skin e.g.: dry and acidic, keratin, erosion of skin removes microorganisms, toxic fatty acids,
normal skin microbiota (competition), antimicrobial peptides (defence)
- Mucosa e.g.: lysozyme for breakdown of peptidoglycan (in e.g. tears/saliva/human milk)
- Lactoferrin (in e.g. saliva, tears, nasal secretions)
But also biological contamination by ciliated epithelium, stomach (acidic environment, denaturation
of peptides), enzymes in the GI-tract, microbiota, immune system, quick local response.
Origin of microbial contamination:
Primary: at premises or during preparation, personnel / raw materials / water / air / equipment /
packaging
Secondary: during storage, transport and administration
Prevention and mitigation of the risk of microbiological contamination
P. Microbiology
Media, cell wall pH microbiology
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