Outsmarting Antimicrobial-Resistant Pathogens

The evolution of antibiotic resistance in bacteria is occurring at an alarming rate and is outpacing the development of new countermeasures.

—White House Office of Science and Technology Policy, September 18, 2014

In the contest between humans and pathogens, each faction has an evolutionary advantage: we have the brains to plot antimicrobial strategies but they have the means to defeat them through rapid reproduction, genetic selection, and recombination. Pathogens act faster, so we have to act smarter.

CDC’s recent report on antibiotic resistance threats estimated that 2 million people each year are infected with antibiotic-resistant bacteria and 23,000 die as a result. This month, the White House issued a new National Strategy on Combating Antibiotic Resistant Bacteria [PDF 481.02 KB]. CDC is working with state, national and international public health partners to address this threat through a combination of preventive strategies, stronger surveillance, and use of innovative diagnostic tests.

Antibiotics are victims of their own success. Following the introduction of penicillin in the 1940’s, medicinal chemists developed many effective new compounds but their extensive use in people and animals has encouraged the emergence and spread of resistant bacterial strains. Antimicrobial resistance has also emerged in viruses, fungi, and parasites. An upsurge in untreatable infections could undermine not only 20^th-century public health achievements in controlling infectious diseases but much of modern medicine, including surgery and chemotherapy.

Of course, humans have evolved their own defenses against infection. Well before the antibiotic era, knowledge of immunity was used to develop vaccines and serums to prevent and treat infectious diseases. Recently, news stories on an experimental drug for Ebola virus infection (Zmapp™*) described it as a “serum,” a term that is rarely used today. Nevertheless, immunology, not chemistry, was the starting point for this cocktail of three genetically engineered monoclonal antibodies against Ebola virus, produced by genetically modified tobacco plants.

Now molecular methods are enabling much closer inspection of pathogen-host interactions and bridging the fields of microbiology and immunology. Better insight into pathobiology could suggest new approaches to developing non-chemical antimicrobial strategies. For example, the authors of a recent article suggested that tolerance-based treatment of HIV infection—focused on increasing the infected patient’s ability to remain well despite high HIV load (host tolerance) rather than reducing viral load (host resistance)—could be “evolution-proof,” although evolution of the virus toward greater virulence remains a possibility.

Metagenomics is an emerging method for describing microbial communities by sequencing all the genomes present within a clinical or environmental sample. Applying this approach to human and animal environments, both internal (e.g., gut microbiomes) and external (e.g., hospitals, farms) offers new insights into microbial ecology and evolution. Since penicillin emerged from the Petri dish, most antibiotics have been developed from natural compounds that are elaborated by one type of microbe to ward off others. Researchers recently demonstrated that mining the human microbiome could identify new antimicrobial drug candidates. The human microbiome has an important role in protecting the human host against colonization by harmful invaders and keeping their numbers in check. In the future, “tending the microbiome” could become a public health prevention strategy.

Metagenomic studies are revealing that human-microbe interactions are more complex and dynamic than previously imagined and that our use of antibiotics may have unanticipated consequences. For example, some epidemiologic and experimental evidence suggests that early-life exposure to antibiotics could predispose children to obesity by altering their gut flora. Given that we live in a microbial world, it may be time for new metaphors, replacing the “arms race,” battles, and outright war against microbes with better intelligence, longer-term strategies, and more enlightened negotiations.

Disclaimers:

The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

*Use of trade names and commercial sources is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, or the U.S. Department of Health and Human Services.