Masters of Evolution: the joke is on us?

Photo:  When I was a student of microbiology, the joke was that one day, microbes would once again rule the world. Perhaps it was no joke. Whether it is the impending total antibiotic resistance in gonorrhea, or the various strains of Staphylococcus aureus  from methicillin (MRSA)  to vancomycin  resistant strains (VRSA), and even methicillin sensitive staph which  seems to have evolved increased virulence over the years, bacteria are outwitting humans at every turn.

For each antibiotic we have either discovered or synthesized, genes for resistance are likely lurking in one bacterial population or another.  And if the gene doesn’t already exist, wait a few weeks or months it will (in one case researchers followed the evolution of vancomycin resistant staph in a patient treated over the course of three months.)

In an interview about infectious diseases back in 1990, the late Joshua Lederberg, a Nobel Prize winning molecular biologist said, “Some people think I am hysterical, but there are catastrophes ahead. We live in evolutionary competition with microbes – bacteria and viruses.  There is no guarantee that we will be survivors.”  At the time, AIDs had emerged as a killer virus and there seemed little we could do to stop it. Today, MRSA is a bigger killer than AIDs in the U.S. (in part reflecting a reduction in AIDs deaths in this country).

Bacteria are virtuoso’s of evolution (although stay tuned — as I will be writing about viruses some day soon, strong competition for the title). A single bacterium can generate millions within days, providing untold opportunity for new mutations to take hold and potentially undergo selection – leading to increased frequency of resistance genes through what we might consider more traditional processes.  If new mutations were the only tool in a bacterium’s evolutionary war chest, we might have a fighting chance.  But as it turns out, bacteria had the goods well before we walked or even crawled upon Earth.  A recent paper by Kirandeep Bhullar and colleagues  (PLOSone, 2012), reports finding resistance in bacteria protected from human influence, collected from a location isolated from the rest of the world for over 4 million years.  These are bacteria untainted by industrial age humans, yet they report resistance to fourteen different antibiotics.  Even that finding would be a relative non-issue if bacteria behaved like simple clonal life forms – sending on their DNA in a purely vertical manner (from mother cell to daughter cells ad infinitum), holding tight to their genetic traits.

But when it comes to sharing DNA bacteria are incredibly promiscuous. As bacteria intermingle in close-quarters whether on your skin or in your gut they are constantly sending out hair-like pili a sort of conduit for the ring-like DNA plasmids. With all the DNA being swapped it’s like every moment is prom-night for bacteria.  Plasmids carry all sorts of accessory genes that may come in handy, like genes for a toxin, or enzymes which turn a complex organic contaminant into a meal, or genes for antibiotic resistance.  In fact bacteria share so much DNA that any one bacterial “family tree” is more realistically depicted as a complex “family web.” (I’ll refrain from making a human analogy here.)

Given the genetic tool box available to bacteria whether it causes a skin infection, gonorrhea or pneumonia, resistance is to be expected.  So how do we avoid the fate of the dinosaurs – some of the largest creatures on earth — as a result of the smallest creatures on earth?

In 2011 a group of thirty scientists created a “priority list of steps” towards resolving the looming antibiotic resistant catastrophe.   One outcome was an essay, Tackling Antibiotic Resistance  (Nature Reviews, 2011), in it they write, “It is indisputable that antibiotic resistance is life-threatening in the same sense as cancer both in the number of cases and the likely outcome, thus the following actions can and must be taken as a matter of extreme urgency.”  One of the most obvious actions is reduction, reduction, reduction. We’ve squandered precious and effective drugs because we had little respect for the power of evolution, and insufficient understanding of bacterial genetics.  Now we know better (though really we ought to have known better way back in 1940, when Alexander Fleming, who discovered penicillin first warned us), and the first step is to rein in antibiotic use. Seemingly obvious, but easier said than done. I can recall the days when the kids were young and a bottle of amoxycillin was a common in our own ‘fridge as milk. Our consumer culture expects action, and expects it now. But it’s not just our culture, in many other countries, antibiotics are available over the counter. Try telling someone from one of those countries, sorry, but you’ll need to first see a doctor (if you are even able), and then hope she writes a prescription.  No matter, that a good number of infections are viral and so would not be responsive, or that some bacterial infections can be resolved by a healthy immune system, or that infections are often treated before a doctor knows if the bacteria would be sensitive to said treatment.

Tackling resistance and reining in use is not only imperative it is a major undertaking which, suggests the group will require: public education about bacteria and antibiotic resistance; improved public health and sanitation; development of new antibiotics – an activity which has been largely dropped by major pharmaceuticals which see little profit in drugs which must be treated as precious resources rather than doled out to whomever is willing and able to pay; ending non-therapeutic uses in the agricultural industries; and development of non-antibiotic approaches like vaccines, or probiotics (enabling nonpathogenic bacteria to displace pathogenic bacteria for example).

We must understand not only how microbes evolve resistance but also how microbial reservoirs of resistance genes live, travel and intermingle – whether residing in and on humans, livestock, in soil and water.  “The cost of the undertaking that we propose,” they write, “will be infinitesimally small in comparison to the economic and human cost of doing nothing.”

For more on evolution and antibiotic resistance see: Origins and Evolution of Antibiotic Resistance by Julian and Dorothy Davies (Microbiology and Molecular Biology Reviews, 2010, p. 417-433) and Are antibiotics naturally antibiotics by Julian Davies, (J Ind Micro Biotecnol, 2006, 33: 396-499.)

For a really informative map of resistance by drug or bacteria or even region see

The Center for Disease Dynamics, Economics & Policy site; there you can find out things like if you are to become infected by staph you’ll have better luck with treatment in Scandinavia  where resistance rates run around 2% than in the US where the resistance rate is 51.3%.

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