On the Trail of Drug-Defying Superbugs

By Elia Ben-Ari
Posted June 13, 2014

Some of the bacteria that cause infections in humans have become resistant to the antibiotics we use to combat them. Antibiotic resistance can turn once-manageable infections into "superbug" diseases that are difficult—and sometimes impossible—to treat. According to the Centers for Disease Control and Prevention, in the United States alone, at least 2 million people each year develop serious infections with drug-resistant bacteria, and about 23,000 die.

Scientists funded by the National Institutes of Health are studying many aspects of antibiotic resistance, including how it spreads. Here are just a few examples of what they're exploring and how it could aid efforts to curb the emergence of resistance.

Detecting New Sources of Antibiotic Resistance

David Cummings, professor of biology, Point Loma Nazarene University in San Diego David Cummings studies the role of urban storm water in spreading genes for antibiotic resistance in natural environments. Credit: Marcus Emerson, Point Loma Nazarene University.

The most common way that bacteria become invulnerable to antibiotics is through the transfer of resistance genes from other bacteria. Often, these genes are found on small, circular pieces of DNA called plasmids that are readily passed among bacterial species.

David Cummings of Point Loma Nazarene University in San Diego searches for plasmids bearing resistance genes in sediment samples from several urban wetlands. These habitats provide ideal conditions for bacteria from diverse sources, such as human sewage, animal waste and naturally occurring plant and soil microorganisms, to swap genes and spread antibiotic resistance, he notes.

So far, Cummings has found that during winter rains, the coastal wetlands in San Diego receive runoff containing antibiotic-resistant bacteria and plasmids, which can persist in the wetlands at low levels into the dry summer months. Some of these plasmids contain genes that confer resistance to commonly used antibiotics, including beta-lactam drugs like penicillin and cephalosporins and fluoroquinolones like ciprofloxacin (Cipro).

By better understanding the nature of drug resistance plasmids in urban wetlands, Cummings hopes to aid future efforts to prevent their potential spread among bacteria that cause human disease. It remains to be seen whether drug-defying bacterial genes that accumulate in the wetlands are likely to move into other species of harmful bacteria and then to us.

Checking the Gut to Head off Resistance

Antibiotic-resistant strain of Staphlyococcus aureus bacteria. Antibiotic-resistant strains of Staphylococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH's National Institute of Allergy and Infectious Diseases.

Bacteria living in the human body can trade resistance genes, too. Gautam Dantas of Washington University School of Medicine in St. Louis is investigating how resistance develops in and spreads among the bacteria that colonize the human gut during the first 2 years of life.

As soon as babies emerge from the womb, they start picking up microbes from their moms, their caregivers and the environment. The human intestinal tract, in particular, harbors hundreds of microbial species, many of which are harmless or even beneficial to their hosts.

"The first 2 or 3 years of life are when the real action occurs in terms of setting up the network of microbes in the human gut," says Dantas. But taking antibiotics can promote the emergence of drug-resistant strains of bacteria by favoring the proliferation of "bugs" that can evade the drugs. And kids from birth to age 5 are given more antibiotics per capita than any other age group, he adds.

Dantas is studying the development of the complete collection of resistance genes in the gut—dubbed the resistome—in healthy sets of twins and in infants with very low birthweights. By cataloging the abundance and diversity of these genes in fecal samples taken from infants at regular intervals and looking at how they change over time, he hopes to gain insights on how the gut resistome is affected by antibiotic treatment, genetics and other factors.

"This is a way to detect resistance genes before they [transfer into disease-causing bacteria and] become a problem," says Dantas. His work also could lead to a more informed strategy for antibiotic use in kids to minimize the risk that bad bugs will survive and multiply.

Modeling the Spread and Control of Resistance

Staphylococcus aureus (staph) bacteria often coexist peaceably with humans, hanging out on body surfaces like the nose or skin without ill effects. Roughly a third of the general population is harmlessly colonized with this form of staph bacteria, and most people don't develop an active infection.

In the past decade, though, certain virulent, antibiotic-resistant strains of staph, known as methicillin-resistant Staphylococcus aureus, or MRSA, have spread rampantly in the general community. These so-called community-associated MRSA (CA-MRSA) infections have become the most common cause of skin infections seen in hospital emergency departments and can turn deadly if they spread to the bloodstream or internal organs, says Diane Lauderdale of the University of Chicago.

To understand how patterns of contact and behavior among individuals affect the spread of CA-MRSA, Lauderdale and Charles Macal of Argonne National Laboratory developed a computer model representing the real-world interactions of the Chicago metropolitan area population in households, schools, workplaces, gyms, hospitals, prisons and other settings. The scientists fine-tuned the model to simulate retrospectively the actual spread of CA-MRSA that occurred in the city from 2001 to 2011.

The model revealed that more than 90 percent of CA-MRSA infections were due to contact with a colonized, symptom-free individual. It also indicated that households were by far the most common site of infection, followed by schools. These findings, Lauderdale says, point the way to strategies that are most likely to curb the spread of drug-resistant staph in the community, such as disinfectant treatments targeting affected households, which the researchers can then test using their virtual version of the Windy City.

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This Inside Life Science article also appears on LiveScience.