Transcript Bacteria are ubiquitous, we can`t beat them

Control of Microbial Populations: Chapter 7
--- Bacteria are ubiquitous, we can’t beat them (and in many
ways we would not want to even if we could), but we can learn to
control where and at what rates they do grow if we keep in mind that
bacteria are constantly evolving.
Methods of Sterilization:
Dry Heat
Boiling
Moist Heat (Autoclave)
Radiation
Chemical Disruption
Filtration
--- Keep in mind that in sterilization you must kill all bacteria,
so the technique must be harsh enough to kill even the toughest
bacteria that could possibly be present, generally that means the
endospore forming bacteria (Bacillus cereus, et. al.)
Dry Heat
Basically baking bacteria to death,
Not very efficient
Works for glass or metal surfaces
No good for media or most chemicals
Boiling
As the name implies, treatment with boiling water
Will kill most pathogenic bacteria, viruses, and fungi
Won’t kill many of the soil endospore formers
Moist Heat:
An autoclave is basically a big pressure cooker (at 15 psi
water boils at 121 C)
Very effective for most liquid and dry materials
Keep in mind that heat transfer limits how fast materials
reach 121 C
autoclave rule of thumb: 20 min/ liter
Radiation
Any type of radiation that causes molecular damage (particularly
to DNA) can be used to sterilize material, the important things to keep
in mind are exposure time and depth of penetration
Ultraviolet (UV)
good for sterilizing surfaces, will kill most bacteria
very effective at damaging DNA (Thymine dimers)
Ionizing Radiation
much more penetrating power
may cause chemical changes in over-exposed material
Filtration
Physically remove bacteria and or viruses
can separate viruses from bacteria
good for heat/ radiation sensitive materials (drugs, antibiotics, etc.)
may leave some soluble materials behind (LPS endotoxins)
Not So Sterile, Sterilization
Pasteurization
Brief heating kills many, but not all bacteria
Most pathogens are less hardy and/or do not grow well
outside of the host and if enough are killed they will be too few to
initiate a new infection
has been very effective for wine, beer, and milk
Oddball aside (when aesthetics trump health):
CO treatment of meat
Chemical Warfare
Disinfectant: kills cells on contact, generally through chemical
reaction non-specific will kill any cell
Antiseptic: Kills bacteria but does less damage to eukaryotic
cells ( example H2O2), still relies mostly on basic
chemistry generally not used internally
Antibiotic: A chemical compound that kills bacteria specifically,
usually without reactive chemistry, but by blocking some
essential cellular function, can be used internally
Antibiotics
Sulfa drugs:
A class of molecules that inhibit biosynthetic reactions
developed during the 1920 &30’s
can be taken internally, but many were not well tolerated
some still used today
Modern Antibiotics
Penicillin was the first discovered in 1929 but was not
brought to production until the early 1940’s
Many come from the conflict between different bacteria
and between bacteria and fungi
Over 100 are known, not all are completely selective
against bacteria
The Penicillin Story
First discovered by Alexander Fleming (a British doctor and
researcher) in 1929. Fleming had an interest in
natural products that could inhibit bacterial infection,
he is also known for the discovery of human lysozyme.
Fleming was not a chemist and was not successful in producing
a molecule that would be useful in medicine.
It took Fleming a decade to interest a biochemist in his penicillin project.
Howard Florey and his group started on the project in 1938, and
by 1940 had a therapeutically useful molecule.
It is estimated that penicillin has saved over 200 million lives
Collaboration in Science
“Chance favors the prepared mind”
--- Louis Pastuer
Aminoglycosides: (Streptomycin, Gentamycin) Inhibit protein synthesis by binding
to a portion of the bacterial ribosome. Most of them are bacteriocidal (i.e., cause
bacterial cell death).
Bacitracin: Inhibits cell wall production by blocking the step in the process
(recycling of the membrane lipid carrier) which is needed to add on new cell wall
subunits.
Beta-lactam antibiotics: A name for the group of antibiotics which contain a
specific chemical structure (i.e., a beta-lactam ring). This includes penicillins,
cephalosporins, carbapenems and monobactams.
Cephalosporins: Similar to penicillins in their mode of action but they treat a
broader range of bacterial infections. They have structural similarities to penicillins
and many people with allergies to penicillins also have allergic reactions to
cephalosporins.
Chloramphenicol: Inhibits protein synthesis by binding to a subunit of bacterial
ribosomes (50S).
Glycopeptides (e.g., vancomycin): Interferes with cell wall development by
blocking the attachment of new cell wall subunits (muramyl pentapeptides).
Macrolides (e.g., erythromycin) and Lincosamides (e.g., clindamycin): Inhibit
protein synthesis by binding to a subunit of the bacterial ribosome (50S).
Quinolones: (Novobiocin) Blocks DNA synthesis by inhibiting one of the
enzymes (DNA gyrase) needed in this process.
Rifampin: Inhibits RNA synthesis by inhibiting one of the enzymes (DNAdependent RNA polymerase) needed in this process. RNA is needed to make
proteins.
Tetracyclines: Inhibit protein synthesis by binding to the subunit of the bacterial
ribosome (30S subunit).
Trimethoprim and Sulfonamides: Blocks cell metabolism by inhibiting enzymes
which are needed in the biosynthesis of folic acid which is a necessary cell
compound.
Using antibiotics
b-lactams are often not prescribed for Gram (-) bacteria,
Why not?
In general it is best to have at least a good idea of what group
of bacteria is involved in the disease.
Also, these days, one must consider patterns of resistance that
may be common in your geographic area.
Antibiotic Resistance
Bacteria evolve, adapting to rapidly changing conditions is the
broadest description of their niche. So it should not surprise us that
within ten years of its introduction, resistance to penicillin was well
documented and widespread.
Overuse and misuse of antibiotics plays to the strengths of
bacterial adaptation. What does not completely kill them only makes
them stronger.
The Problem
Antibiotics are seen as a “magic bullet” that cures all bacterial
problems. We need to focus more on other ways to control bacteria and
save antibiotics as a treatment of last resort for acute infections.
Annul Antibiotic use in the United States (2002)
35,000,000 pounds of antibiotics used annually
13% in human medicine
6% therapeutics use in agriculture
78% non-therapeutic use in agriculture
6% use in pets
from: Shea., M., K: Pediatrics, vol.112, No.1, July 2003.
Mechanisms of Antibiotic Resistance
1.) Cleavage (penicillinase)
2.) Chemical modification (kanamycin methyl transferase)
3.) Efflux pumps (pump it back out of the cell)
4.) Mutation in the affected protein (mutations in ribosomal
proteins can lead to resistance to erythromycin)
Potentially any of these mechanism are transferable by HGT
Solutions to Antibiotic Resistance:
1.) Work on overuse (in medicine and agriculture)
--- reduce selective pressure
2.) Prevent spread of resistance mechanisms
3.) Massive overkill strategies in medicine (no survivors= no
adaptation)
4.) Work with bacterial ecology (competition with innocuous
strains, Probiotics, or natural bacterial predators)
5.) In the short term, develop more truly new antibiotics