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Two Hundred Thousand Lurking Germs

Microbecide® Special Report

Two hundred thousand germs could easily lurk under the top half of this semicolon;

A single bacterium – a microbe - is only about three microns long. With a tough, armored, outer cell wall, it is shaped somewhat like a railway tank car. Viruses are even smaller and are the most basic of all microorganisms. They contain only nucleic acid (DNA or RNA) and a protein coat cover. Some more complex viruses are enclosed in a protective envelope derived from infected microbes own cell membrane. Viruses require the help of other microbes to reproduce.

Bacteria, fungi, chlamydia are more complex and have a nuclear body (DNA or RNA) and cytoplasm that contain components that convert nutrients into energy to drive the microbe’s functions. These microorganisms can reproduce on their own.

The nucleus of a microbe can be viewed as the control center and the cytoplasm the factory. Viruses have a control center but no cytoplasm, a virus is dependent on the microbe it infects to provide the factory it needs to produce energy or reproduce itself.

Microbes live anywhere damp.  In water.  In mud.  In the air, as spores and on dust specks.  In melting snow, in boiling volcanic springs.  In the soil, in fantastic numbers.  All over the planet's ecosystem, any liquid with organic matter, or any solid foodstuff with a trace of damp in it, anything not salted, mummified, pickled, poisoned, scorching hot or frozen solid, will swarm with microbes if exposed to air.

Microbes live on and inside human beings.  They creep onto us in the first instants in which we are held in our mother's arms.  They live on us, and especially inside us, for as long as we live.  And when we die, then other microbes break down our remains into raw materials for the microbe factory.

Tank Car Size Microbes

Let us imagine (for the purpose of exploring the world of microorganisms) that a microbe is about the size and shape of a real railway tank car.  Now, we can peer inside, examine how microbes survive and replicate, learn how they mutate and adapt to defend against attacks by antimicrobial agents and most importantly, understand how Microbecide® antimicrobial products overcome all their defenses.
Microbecide® Silver Ion Complex
The first thing we notice about our tank car microbe is the long, powerful whips that are corkscrewing at a blistering 12,000 revolutions per minute.  When it's got room and a reason to move, the microbe can swim ten body-lengths every second.  The human equivalent would be sprinting at forty miles an hour.

The butt-ends of these spinning whips are firmly socketed inside rotating, proton-powered, motor-hubs. It seems very unnatural for a living creature to use rotating wheels as organs, but microbes are untroubled by ideas of what is natural.

The microbe, constantly chugging away with powerful interior metabolic factories, is surrounded by a cloud of its own greasy mucus.   The rotating spines, known as flagella, are firmly embedded in the microbe's outer hide, a slimy, lumpy, armored bark.  The outer cell wall is a double-sided network of interlocking polymers, two regular, almost crystalline layers of macromolecular armor.

The netted armor, wrinkled into warps and bumps, is studded with hundreds of busily sucking and spewing orifices.  These are the microbe's "porins," pores made from wrapped-up protein membrane, something like damp rolled-up newspapers that protrude through the armor into the world outside.

On our scale of existence, it would be very hard to drink through a waterlogged rolled-up newspaper, but in the tiny world of a microbe, osmosis is a powerful force.   The osmotic pressure inside the microbe can reach 70 pounds per square inch, five times atmospheric pressure.

The microbe boasts strong, highly sophisticated electrochemical pumps working through specialized fauceted porins that can slurp up and spew out just the proper mix of materials.  An efficient factory, the microbe can pump enough materials to double in size in a mere twenty minutes.  In that same twenty minutes, the microbe can also build an entire duplicate of itself from scratch.

Inside the outer wall of protective bark is a greasy space full of chemically reactive ooze.  It's the periplasm.  Periplasm is a treacherous mass of bonding proteins and digestive enzymes, which can pull fragments of building materials right through the exterior hide, and break them up for further assimilation, rather like chemical teeth. The periplasm also features chemoreceptors, the microbial equivalent of nostrils or taste-buds.

Beneath the periplasmic ooze is the interior cell membrane, a tender and very lively place full of elaborate chemical scaffolding, where pump and assembly-work goes on.

Inside the interior membrane is the cytoplasm, a rich ointment of salts, sugars, vitamins, proteins, and fats, the microbe's factory and treasure-house.

Multi Cell vs Single Cell

Microbes are both primitive and highly sophisticated -- and vastly different from us multicellular mammals.  Eukaryotic cells -- we humans are made from eukaryotic cells -- possess a neatly defined nucleus of DNA, firmly coated in a membrane shell.  Microbes are prokaryotic cells, the oldest known form of life. Microbial DNA simply sprawls out amid the cytoplasmic ooze in a series of circular double-helix snarled and knotted configurations.

Plasmids And Transposons

A microbe usually has 200,000 or so clone microbial sisters around within the space of a pencil dot, cloning themselves every twenty minutes. Microbes share enormous amounts of DNA.

A plasmid is an alien DNA ring. Transposons are sequences of DNA that can move around to different positions within the genome of a single microbe, cause mutations, and change the amount of DNA in the genome.

Microbes not only share DNA among members of their own species, through conjugation and transduction, but they will encode DNA in plasmids and transposons and transmit it to other species.  They can even find loose DNA from the burst bodies of other microbes, and take in that DNA like food and then make it work like information.  Pieces of stray DNA can be swept into the molecular syringes of viruses, and injected randomly into other microbes.

Microbes do extremely strange and highly inventive things with DNA.  This property of microbes is very unique.  For example, if your lungs were damaged, and you asked your dog for a spare lung, and your dog produced a lung and gave it to you, that would be quite an unlikely event.  It would be even more miraculous if you could swallow a dog's lung and then breathe with it just fine, while your dog calmly grew himself a new one.  But in the world of microbes this kind of miracle is commonplace. 

When an antimicrobial agent is introduced into an environment, mass death of microbes will result.  But any bug (microbe) that is resistant will swiftly multiply by millions of times, thriving enormously in the power-vacuum caused by the destruction of other microbes. The genes that gave the lucky winner its resistance will also increase by millions of times, becoming far more generally available.  And that’s not all, often the resistance is carried by plasmids, and one single microbe can contain as many as a thousand plasmids, and produce them and spread them at will.  

Cassettes

A resistance plasmid (R-plasmids) has plenty of room inside a ring of plasmid DNA for information on a lot of different products and processes.  Moving data on and off the plasmid, scissors-and-zippers units, transposons, can knit plasmid DNA right into the microbe’s DNA -- or they can transpose new knowledge onto a plasmid.  These segments of loose DNA are known as "cassettes."  

Some of the best and cleverest information-traders are some of the worst and most noxious microbes.  Such as Staphylococcus (boils), Haemophilus (ear infections), Neisseria (gonorrhea), Pseudomonas (abcesses, surgical infections).   Even Escherichia, a very common human commensal microbe.

Agents, Tactics and Defenses

Antimicrobial agents break open cell walls, choke off the life-giving flow of proteins, and smash or poison microbial DNA, the microbe’s central command and control center.

When the cell wall of a microbe bursts from osmotic pressure, the effect is known as "lysing."  Microbe cell walls are mostly made from peptidoglycan, a plastic-like molecule chained together to form a tough, resilient network.  Peptidoglycan serves a structural role in the microbial cell wall, giving the wall shape and structural strength, as well as counteracting the osmotic pressure of the cytoplasm. Peptidoglycan is also involved in binary fission during microbial reproduction. A microbe is almost always growing, repairing damage, or reproducing, so there are almost always raw spots in its cell wall that require construction work.

Gram-negative microbes have a double cell wall, with an outer armor plus the inner cell membrane, rather like a rubber tire with an inner tube.  But gram-positive microbes are more lightly built and rely on a single wall only.

Agents such as tetracycline, streptomycin, gentamicin, and chloramphenicol break-up or jam-up the microbe's protein synthesis.  These agents creep through the porins deep inside the cytoplasm and lock onto the various vulnerable sites in the RNA protein factories. This RNA sabotage brings the cell's basic metabolism to a halt, and the microbe chokes and dies.

Another major method of attack is an assault on microbial DNA.  Compounds, such as the sulphonamides, the quinolones, and the diaminopyrimidines, gum up microbial DNA itself, or break its strands, or destroy the template mechanism that reads from the DNA and helps to replicate it. Or, they can ruin the DNA's nucleotide raw materials before those nucleotides could be plugged into the genetic code.

Microbial Resistance

Microbes have evolved to defend against these attacks.  It begins outside the cell, where certain microbes have learned to eject defensive enzymes into the cloud of enzymes that surrounds them. At the cell wall itself, microbes have evolved walls that are tougher and thicker.  Other microbes have lost certain vulnerable porins, or have changed the shape of their porins so that antimicrobial agents will be excluded instead of inhaled.

Inside the cell wall, microbes make permanent stores of enzymes in the outer mass of periplasm, which will chew up and digest the agent before it ever reaches the vulnerable core of the cell.  Other enzymes have evolved that will crack or chemically smother it.

In the pump-factories of the inner cell membrane, new pumps have evolved that specifically latch on to an antimicrobial agent and spew it back out of the cell before it can kill.  Other microbes have mutated their interior protein factories so that the assembly-line no longer offers any sabotage-sites for a protein-busting agent. 

Yet another strategy is to build excess production capacity, so that instead of two or three assembly lines for protein, a mutant cell will have ten or fifty, requiring ten or fifty times as much agent for the same effect.  Other microbes have come up with immunity proteins that will lock-on to an antimicrobial agent and make it a useless inert lump.

Sometimes -- rarely -- a microbe will come up with a useful mutation entirely on its own. But spontaneous mutation is not the core of the resistance, far more often, a microbe gains resistance simply through the exchange of genetic data.

Microbiologists have studied only a few percent of the many microbes in nature. Even those microbes that have been studied are by no means well understood. Antibiotic resistance genes may well be present in any number of different species, waiting only for selection pressure to manifest themselves and spread through the gene-pool.

If penicillin is sprayed across the biosphere, then mass death of microbes will result. But any bug that is resistant to penicillin will swiftly multiply by millions of times, thriving enormously in the power-vacuum caused by the slaughter. The genes that gave the lucky winner its resistance will also increase by millions of times, becoming far more generally available. And there's worse: because often the resistance is carried by plasmids, and one single microbe can contain as many as a thousand plasmids, and produce them and spread them at will. That genetic knowledge, once spread, will likely stay around a while.

Unless they are killed, microbes just keep splitting and doubling. After billions of generations, and trillions of variants, there are still likely to be a few random old timers around identical to ancestors from some much earlier epoch. Furthermore, microbial spores can remain dormant for centuries, then sprout in seconds and carry on as if nothing had happened.

It seems likely that many of the mechanisms of microbial resistance were borrowed or kidnapped from microbes that themselves produce antibiotics. The genus Streptomyces, which are filamentous, Gram-positive bacteria, are ubiquitous in the soil; in fact the characteristic "earthy" smell of fresh soil comes from Streptomyces' metabolic products. And Streptomyces bacteria produce a host of antibiotics, including streptomycin, tetracycline, neomycin, chloramphenicol, and erythromycin.

Today’s Battleground

An adult human being carries about a solid pound of commensal microbes in his or her body; about a hundred trillion of them.  Humans have a whole garden of specialized human-dwelling microbes -- tank-car E. coli, balloon-shaped staphylococcus, streptococcus, corynebacteria, micrococcus, and so on.  Although microbes can be profoundly destructive to the human body, normally these do us little harm.  Our normal human-dwelling microbes act as a kind of protection, monopolizing the available nutrients and forcing out other rival microbes that might be harmful or dangerous. 

The greatest battlegrounds of microbial warfare today are hospitals.  Increasingly, to enter a hospital can make people sick.  This is known as "nosocomial infection," from the Latin for hospital.  About five percent of patients who enter hospitals nowadays pick up an infection from inside the hospital itself.

Staphylococcus aureus, a common hospital superbug which causes boils and ear infections, is now present in super-strains highly resistant to every known antibiotic except vancomycin.  Enterococcus is resistant to vancomycin, and it has been known to swap genes with staphylococcus. Staphylococcus often lurks harmlessly in the nose and throat.

Staphylococcus epidermis, a species which lives naturally on human skin, rarely causes any harm, but this harmless species may serve as a reservoir of DNA data for the microbial resistance of other, truly lethal microbes.  Certain species of staph cause boils, others impetigo.  Staph attacking a weakened immune system can kill, attacking the lungs (pneumonia) and brain (meningitis).  Staph is thought to cause toxic shock syndrome in women, and toxic shock in post-surgical patients.

An epidemic of acquired immune deficiency has come at a particularly bad time.  The patients are just one aspect of the problem, though healthy doctors and nurses show no symptoms, they can carry strains of hospital superbugs from bed to bed on their hands, deep in the pores of their skin, and in their nasal passages. 

Nowadays half of nosocomial infections are either surgical infections, or urinary tract infections from contaminated catheters. Microbes attack us where we are weakest and most vulnerable, and where their own populations are the toughest and most battle-hardened. From hospitals, resistant superbugs travel to old-age homes and day-care centers, predating on the old and the very young. 

Superbugs show up in food, fruit juices, bedsheets, even in bottles and buckets of antiseptics. The advent of antibiotics made elaborate surgical procedures safe and cheap; but nowadays half of nosocomial infections are either surgical infections, or urinary tract infections from contaminated catheters.

Infectious microbial contaminations are very real threats today and increasing at considerable speed. Strains of pathogenic microbes can cross the planet with the speed of jet travel, and populations of humans -- each with their hundred trillion microbial passengers -- mingle as never before.

New, major breakthroughs in ionic silver technology and combinatorial chemistry are now equipping us with extraordinary new defenses to combat ever increasing health threats. The need for new, game-changing antimicrobial tools has never been greater, infectious disease is fast becoming one of the greatest menaces we human beings confront.

 

Bruce Sterling bruces@well.sf.ca.us

 



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