Humans May Lose Battle With Bacteria, Medicinal Chemist's Research Shows

It may not be an ideal topic for polite conversation, but human beings are swarming with bacteria: Even the average healthy adult plays host to about 100 trillion microscopic organisms. Infection takes place when the bacteria get out of hand.

Now, a University of Kansas researcher has penned a history of the struggle between man and bacteria — and warns that humankind someday may lose its advantage.

In the March 28 issue of the American Chemical Society’s Journal of Natural Products, Lester A. Mitscher, a University Distinguished Professor of Medicinal Chemistry, calls for the development of more potent antibiotics necessary for humanity to manage drug-resistant breeds of microbes.

“Antibiotics are essentially selective poisons that kill bacteria and that do not kill us,” Mitscher said.

In his article, “Coevolution: Mankind and Microbes,” Mitscher chronicles the advent of antibiotics in the 20th century. Sulfonamides, the first anti-infectives, were introduced the mid-1930s. Penicillin — “the first true antibiotic” — was employed widely during World War II. In the decades since, dozens of important antibiotics have been developed and marketed around the world.

“These were called ‘miracle drugs,’ ” said Mitscher. “Unfortunately, that had a downside. They were so relatively safe and so effective that we became careless in their use and in our personal habits. That has caused much of the resistance phenomenon we have today.”

Microbial resistance to these drugs has been an ever-increasing problem because of the speedy reproduction and evolution of microorganisms.

“Bacteria that survive the initial onslaught of antibiotics then are increasingly resistant to them,” said Mitscher. “The sensitive proportion of the bacterial population dies, but then the survivors multiply quickly — and they are less sensitive to antibiotics. The sensitivity goes all the way from requiring a longer course of therapy or a higher dose, to being totally unaffected by the antibiotic.”

Humans have overused antibiotics in areas such as agriculture, worsening the dilemma of highly resistant bacteria.



“People are surprised to learn that almost half of all the antibiotics produced in the world are used in animal husbandry,” said Mitscher. “I’m not referring to using antibiotics for curing infections of animals — what I mean is use of antibiotics in relatively small doses as an animal-feed supplement. Animals then grow quicker to a marketable size, and this is seen as a universal good. The difficulty is that use of antibiotics in that setting is an invitation towards resistance. Unfortunately, humans get infected with resistant strains that were generated in animals in this manner.”

These days, with so-called “super-bugs” like Methacillin-resistant Staphylococcus aureus (MRSA) making news, resistance is becoming a major public health problem.

“Resistance that started in a hospital setting quickly spread into the community, and now resistance is essentially all around us,” Mitscher said. “That does not mean to say we’re all going to die in agony in the immediate future. But this is an important phenomenon that needs to be addressed more carefully than we have in the past.”

Part of the solution is to use antibiotics sparingly for industrial, agricultural and medical purposes. When an antibiotic is called for to treat an infection the best one should be used with appropriate intensity.

Mitscher said that drug corporations must develop antibiotics with the potential not only to kill microbes but also to inhibit their ability to mutate. These new drugs would be made more effective still if they enlisted the body’s own immune system to battle infections.

Alas, because of the economics of the drug industry, Mitscher said such “triple treat” antibiotics might be a long time coming.

“The pace of antibiotic discovery has fallen off, partly because the intensive research on them has lead to increasingly diminishing returns,” said Mitscher. “Pharmaceutical firms have, for a variety of commercial reasons, de-emphasized antibiotic research in recent decades.” - sd