Friday, June 22, 2018

Microbes Über Alles: Life at Maximum Zoomm

Deinococcus radiodurans
(“Conan the Bacterium”)
We humans like to think of ourselves and other creatures with backbones as Earth’s dominant life forms. Perhaps that’s because on the surface of things there seems quite a lot of us; we’re easily observable with the naked eye; and from our perspective we account for most of the important stuff, good or bad, that takes place on the planet.

But nothing could be further from the truth. Tiny, single-celled bacteria – approximately 5x10³⁰ or five nonillion of them – make up the majority of the life in this world. Their cumulative biomass exceeds that of us vertebrates by far. Every teaspoon of sea water, for example, contains five million – more in the oceans, that is, than stars in the known universe.

With numbers like that, it should come as no surprise that microbes exert an enormous influence on the biosphere. Many, particularly the cyanobacteria, use sunlight the same way plants do to produce oxygen and sugars. Indeed, the amount of oxygen they generate in the world’s oceans equals that produced by all plant photosynthesis on dry land.

Deinococcus radiodurans is able to deflect a  sur-
prising array of assaults.
Most microorganisms either benefit us or do no harm – fortunate since each of us plays host to some 100 trillion of them. They outnumber our own cells ten to one and account for nearly all of the unique genes in our bodies. To the extent that we're carriers of genetic information, more than ninety-nine percent of it is microbial. Yet fewer than a hundred bacterial species – сold comfort for germaphobes, no doubt – are believed to cause disease in humans. Indeed, if you consider the bigger picture, infectious disease may be the least significant aspect of our relationship with microbes.

Opined Richard Dawkins in his landmark book, The Selfish Gene, “Despite the principle of ‘survival of the fittest,’ the ultimate criterion which determines whether a [gene] will spread is not whether the behavior [benefits] the behaver, but whether it [benefits] the gene…”

Maybe so, but which genes would these be?  Ours or those of our microbial fellow travelers? Stanford microbiologist Justin Sonnenburg suggests that perhaps we ought to think of  the human body as “an elaborate vessel optimized for the growth and spread of our microbial inhabitants.”  He sees people not just as individuals, but also as ecosystems, the mammalian component of which is merely one part of the system.

Radiococcus deejaydurans can withstand hours
of heavy metal and acid rock (not to mention talk radio).
Geobiologists speculate it may have hitched a ride to
earth on a meteorite. Remarkably, it shares most of the
human genome.
Remember Master Blaster, the dynamic duo from Mad Max Beyond Thunderdome (1985)? Master was a brainy but otherwise powerless dwarf who rode piggyback on the enormous but dim-witted Blaster, piloting him about for his (Master’s) own purposes like a Lipizzaner put through dressage. Together they held sway over Bartertown, a market settlement situated in the midst of a post-apocalyptic wasteland. Despite his diminutive size, Master with the help of Blaster was able to work his will unimpeded in Bartertown, while Blaster maybe found some sort of direction and purpose. Today, this setup might be roughly analogous to the one we humans enjoy with our own microbiome.

Take the protozoan parasite Toxoplasma gondii, for example. It’s been found that contact with T. gondii can make men more likely to crash motor vehicles and do risky behavior. They also become more aggressive and jealous. For their part, women appear more likely to commit suicide. T. gondii may also be involved in dementia, bipolar disorder, obsessive-compulsive disorder and autism. To be sure, besides room and board, it’s not clear how T. gondii might benefit, if at all, from modifying it's host behavior.

Yet other alterations in the human gut microbiome  may have still wider effects – e.g., cause greater susceptibility to variety of conditions such as diabetes, neurological disorders, cancer and asthma. Colonic microbes involved in food breakdown have been shown to affect the production of the neurotransmitter serotonin which in turn influences sensorimotor behaviors.

From Wikipedia
Gut bacteria with mind-altering potential are now referred to as ‘‘psychobiotics.’’ Since typically, you get the good with the bad, you have to presume a few troublemakers in this collection, too – “traitor” microbes, say, that secrete substances rendering you paranoid about bacteria themselves, turning you against microbes in general – in other words, making you a hopeless germaphobe.

Or even if not a germaphobe in extremis like Howard Hughes or Howie Mandel, just harboring these bad boys in your colon might be enough to inspire an intuition of germaphobia or who-knows-what else, leading to who-knows-what sorts of mischief. Here in a bit of a twist the expression “You’re full of sh..t!" would denote something fairly specific – the fact that bacteria, which account for 60% of your poop, appeared to have bushwhacked your "free will."

Maybe one of these days, the time-honored “Twinkie defense” will give way to a “bad microbe” one. “Bacteria in my gut made me do it!” Or “Twinkies made my gut bacteria make me do it!”

Et voilà! You have a molecular basis for innocence or guilt, amendable perhaps by a fecal transplant from someone more righteous than you.

“Open wide, son, the court is going to help you get your sh..t together."

Admittedly, my gut reaction to all this, like yours, is “not!,” but maybe that’s just my probiotic (DanActive®) talking. Hey, it could happen! Foods might put words in your colon, leaving you talking out your...

Geobacter metallireducens digesting uranium
waste. Geobacter species use metals as an energy
source the way humans use oxygen. Some may
be helpful in environmental clean-up.
Certainly not all human-associated microbiota are about innocence, guilt, or even disease. Human gut microbes also help us out quite a lot with everyday life. Milk and other food substances, for instance, are full of glycans (polysaccharides) we can’t digest without the aid of bacterial enzymes.

Paradoxically, gut organisms also facilitate the process of weight loss by suppressing the production of a hormone that mediates fat storage and of an enzyme that stops fat from being “burned.“ In June, 2016, researchers at Massachusetts General Hospital, Boston, began a clinical trial (“Fecal Microbiota Transplant for Obesity and Metabolism”) studying the impact of gut bacteria from a healthy, lean person transplanted into the intestinal tracks of obese individuals by means of a small capsule of feces taken by mouth. This could lead to an exciting new way of managing obesity – if you could stomach the “diet.”

To me, one of the most fascinating things about bacteria is a behavior known as “quorum sensing.” Researchers have found that many species are able to detect the amount of a signaling molecule present in their environment and respond only when the concentration of the molecule reaches a specific level. They use this process to regulate various phenotypic behaviors such as biofilm formation, virulence factor expression, motility, and in some cases, bioluminescence, nitrogen fixation and sporulation. In a way, this makes bacteria the inventors of the information-based society, our internet being just an offshoot of a chemical information game that began billions of years ago.
Bacteriophages are viruses that infect bacteria and then exploit their host’s
protein-making machinery  to replicate themselves, ultimately destroying the host.
They’ve been used for decades as an alternative to antibiotics in Russia, France,
and Central Europe.

But if bacteria can do this, why not us? You wonder what sorts of quorum sensing we humans – perhaps entirely unbeknownst to ourselves – might be getting up to.

Could quorum sensing account for the depredations of religious zeal and the need to aggressively proselytize, for example? Maybe the power of “I believe!” reverses the spin on your top quarks flipping you into some comfortable quantum collective that grows stronger with numbers, stabilizing (as “truth”) at some threshold level (the Biblical gathering of two or three might be overly optimistic) of recruitment. Too many non-believers, and the wave function falters, faces collapse, its “truth,” extinction – explaining the compulsion to ruthlessly exterminate heretics.

Just sayin’ – but have you got a better explanation for the urge to kill others who simply have a different mythology?

Finally, among the most intriguing microbes to me are ones we mostly don’t carry around as part of our microbiome – the extremophiles, many of which have upended notions about the nature of life, terrestrial or otherwise. For several of these rely on energy sources foreign to us, sources other than carbon and oxygen, and thrive in environments that would quickly be lethal for other creatures – e.g., extremes of pressure, radiation, acidity, salinity, heat, dryness, anoxia, and environmental pollution (oil, nuclear waste, heavy metals). Some are methane-consuming and inhabit deep ocean floor sediments; others are sulfur-breathers that live in fissures miles below ground.
Who knew a clinical history of mummification and 2000-year entombment
could be so helpful in the diagnosis of viral disease?

One of these, Thermus aquaticus (which only sounds like Latin for “hot water bottle”), recovered from hot (131° F) springs in Yellowstone National Park, was the source of the heat-resistant Taq enzyme used in the polymerase chain reaction (PCR) DNA amplification process, an important research tool in molecular biology.

My favorite extremophile, however, is “Conan the Bacterium” – Deinococcus radiodurans, a polyextremophile listed in Guinness World Records as "the world's toughest bacterium." Able to survive extremes of cold, desiccation, vacuum, acidity, and starvation, it’s also the most radiation-resistant organism known. This it accomplishes by having multiple copies (between four and ten) of its genome and rapid DNA repair mechanisms that allow it to take two copies with random breaks and use them to reconstruct a single intact copy.

Yet its remarkable tolerances are hard to explain. Easily cultured in the laboratory, and not a cause of disease, D. radiodurans is found virtually everywhere – in soil, meat, feces, sewage, dried foods, room dust, and on medical instruments and textiles. It’s been recovered from elephant dung and granite in dry Antarctic valleys (thought to be an environmental approximation of Mars). Selective pressures here on earth, in other words, don’t seem to explain its preternatural hardiness.

U.S. scientists have created a strain of Deinococcus that can degrade toluene, an organic chemical found in radioactive waste sites. Another genetically engineered strain converts mercury, also found at these sites, into a less toxic form. None of which gets rid of the radiation, but does expedite cleanup and saves money.

Could Deinococcus radiodurans be Earth’s last best hope for the future? Isn't is comforting to know that once we humans have managed to eradicate just about every species including ourselves, D. radiodurans is likely to go soldiering on? Perhaps it’ll piggyback onto cockroaches (if there are any), Master Blaster style, to oversee the reconstruction of a brave new world. Or at least some scaled-down version of one – a buggy Bartertown, say, where servile methane-producing microbes live enthralled to gluttonous, methane-gobbling ones; where, just as on Mars, water and oxygen are things of the past, and extremophilic, the new norm.

Where “Conan the Bacterium” rules über alles.

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