Bug to the Future

Bacteria have a few billion years of guerrilla warfare under their belts.” LA Times

You may remember your doctor’s admonition when he or she placed you on a trace of antibiotics: “No matter what, finish the entire prescription; don’t stop until all the pills are gone.” If bacteria were able to express joy, nothing makes a toxic bacteria’s family happier than humans and animals taking only a partial on their antibiotic prescription. It helps that family of bacteria develop and immunity to that particular form of antibiotic “fast and furious.” And there are so many new “superbugs” today – bacteria that have no known effective antibiotic treatment.

Lots of us believe that bacteria evolve immunity to antibiotics through a hit or miss Darwinian process of natural selection. Wait until there is a mutation, and that mutation slowly replaces those members of the species not so well equipped to deal with whatever nature has changed in their environment. Gills to lungs, if you will. Not exactly.

For those super-scientifically inclined, there’s a disturbing study reported in the May 24^th Science magazine with this cryptic title: Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer. Hey, doesn’t that title just say it all? Maybe the above pictures of the efflux pump bacterial structure help? OK, not so much, but the results of that research might be just as troubling to humanity as climate change. We’ve had a hate-hate relationship with bacteria throughout our existence:

“For most of human history, bacteria have had their way with us. Though some of them are helpful, others cause dangerous diseases like pneumonia, cholera and meningitis. The bacterium Yersinia pestis wiped out roughly 20% of the world’s population in the mid-1300s during the pandemic known as the Black Death.

“When scientists first developed antibiotics in the early 1900s, humans enjoyed the upper hand — for a while. Some of the drugs target the machinery that maintains a bacterium’s all-important cell wall. Others rob bacteria of the proteins they need to carry out essential functions or damage the DNA needed to reproduce… It took just a few decades for the first drug-resistant strains to appear. Since then, the invention of each new antibiotic invited a jeering reply.

“Doctors responded by prescribing another antibiotic drug, and another. Then two drugs together. Then three. But now the arsenal is all but depleted, and there are strains of Escherichia coli, Klebsiella pneumoniae, Acinetobacter and Enterococcus that have evolved to overcome almost every medicine thrown at them.

“So scientists are racing to understand superbugs’ tactics. Among the most urgent questions is this: How does antibiotic resistance spread between bacteria cells, even — or especially — in the presence of antibiotics that are designed to knock them back?

“Bacteria know better than to wait around for a random mutation in their DNA that will protect them from antibiotics. Those mutations will come but not often: For some drugs, only about 1 in 10,000 bacteria will develop resistance that way. For other drugs, only about 1 in a billion will do so. Either way, that’s not very efficient.” Emily Baumgaertner writing for the May 25^th Los Angeles Times.

“But not all bacteria are bad. In fact, some bacteria are necessary for us to live, eat, work and feel healthy. Helpful bacteria makes good use of itself in foods, in your garbage can and in your digestive system. Although bacteria generally have a bad reputation, more is being learned about good bacteria and how it helps us every day.” LiveStrong.com. Some of us even take bacterial supplements to aid digestion: probiotics. Scientists are also experimenting with the use of genetically altered viruses to control bacteria and even to convert bacteria to new and unexpected uses: like generating electricity. But for those one-celled critters hell-bent on infecting us, it’s a whole different story. And they hardly rely on random natural selection to build resistance to antibiotics.

“The tiny bacteria that live inside our guts have an ingenious way of withstanding the onslaught of antibiotics we throw at them, according to a report published this week in the journal Science. The two-part system allows bacterial cells to stay alive until another bacterium can deliver a lifeline, packaged in a snippet of DNA.

“‘I’m afraid our findings are great news for bacterial cells — not so good for us,’ said study leader Christian Lesterlin, a researcher in the molecular microbiology and structural biochemistry program at the University of Lyon in France… Lesterlin and his colleagues already knew that superbugs could repel even our most modern medicines. What they didn’t know was how the microbes managed to pull it off.

“These are amazing abilities they have, to be able to adapt and survive in harsh environments with antibiotics,” he said. ‘But the more we understand about it, the more we can do for human health.’…

“Lesterlin’s team wanted to visualize exactly how the exchange worked [the bacteria to bacteria transfer of information]. They put a regular strain of Escherichia coli bacteria in one petri dish and a strain that is resistant to the antibiotic tetracycline in another dish. Then they saturated both plates with tetracycline and watched closely.

“Logic suggested the bacteria cells lacking the ability to resist the drug would die. Instead, they simply went to sleep. After several hours, the researchers combined the contents of the two dishes and used a technique called live-cell microscopy to watch in real time as plasmids were transferred in just two minutes from tetracycline-resistant bacteria cells to tetracycline-sensitive ones.

“Less than two hours later, the plasmid produced a protein called TetA resistance factor, which makes bacteria impervious to tetracycline. That was ‘shockingly counterintuitive,’ Lesterlin said, because tetracycline blocks the production of proteins by binding to the machinery required to make them.

“The next question was this: How could bacteria get away with producing drug-resistance proteins right there in the presence of a protein-inhibiting drug?... As the hosts on QVC might say, one can never have too many accessories… That’s especially true for something called the AcrAB-TolC multidrug efflux pump, which sits on the cell’s outer membrane and ejects various toxic antibiotics that have invaded the cell’s interior.

“Despite the pump’s fancy name, it’s not sufficient to keep the cell thriving amid a surge of antibiotics. But it buys vital time for the groggy cell to acquire a plasmid with an all-important resistance gene… Now that scientists understand the mechanics of plasmid transfers, they can try to create new treatments that attack the multidrug efflux pumps that allow resistance to spread.

“‘Bacteria have multiple weapons — you can’t just shut down one weapon and expect to succeed,’ said Shaun Yang, assistant medical director of the Clinical Microbiology Laboratory at UCLA, who was not involved in the research. ‘From a drug development perspective, that’s significant.’

“For now, scientists remain locked in a race that could mean life or death for all organisms involved. Antibiotic-resistant bacteria already kill at least 23,000 people in the United States a year, according to the Centers for Disease Control and Prevention — an estimate that most experts consider conservative… The United Nations warns that, without action, drug-resistant infections could kill 10 million people annually by 2050. That’s a public health nightmare but hardly a surprise.” LA Times. And bacteria are absolutely everywhere in our environment. We need some of them… and get killed by others.

              I’m Peter Dekom, and what you cannot see sometimes can kill you; sometimes it is the little things that count!