Research in the post-antibiotic era

Here’s how science is answering the WHO’s call to find ways to fight infections after all antimicrobial drugs fail

Antibiotics have always had an expiry date. Bacteria were bound to eventually develop resistance. The question was when, and now we have an answer. In August 2016, a woman in the US was diagnosed with an infection after a hip operation. After running her through antimicrobial susceptibility testing, doctors in Reno, Nevada discovered that the infection was resistant to all 26 known antibiotics. The woman later died of septic shock. This was the first record of bacteria resistant to all antimicrobial drugs in the US.

In February of this year, the World Health Organization published a list of “priority pathogens.” This list was meant to prioritize public health efforts, and put finding new and effective antibiotic treatments firmly on the agenda as a focus in research and drug discovery. Highlighting the urgency, another WHO report in September warned that the world is running out of antibiotics, as “most of the drugs currently in the clinical pipeline are modifications of existing classes of antibiotics and are only short-term solutions.”

So how is the research community responding? In their February report, WHO outlined three pathogens of critical importance: Acinetobacter baumannii, pseudomonas aeruginosa, and enterobacteriaceae. The following graphs show that interest in these three pathogens has been increasing for some time now:

Total number of publications that mention WHO's critical pathogens in their abstract or title:

The number of times publications that mention WHO's critical pathogens in their abstract or title have been read:

As the antibiotic age ends, researchers are developing new and innovative ways to combat bacteria. Here’s an overview of research in the field that’s made the headlines in the past year. Monique van Hoek, a microbiologist at the National Center for Biodefense and Infectious Diseases in the US, designed a synthetic peptide that helps heal infected wounds. The peptide, called DRGN-1, is based on a naturally occurring peptide in the blood of Komodo dragons and works by increasing the permeability of bacterial membranes. Nanoparticles that work alongside standard antibiotics are another promising solution. Once activated by light, the nanoparticles release a superoxide, making the bacteria susceptible to antibiotics they’d otherwise be resistant to. Biologist Bernhard Krismer and his team even went looking for antibiotics in the human nose and found a bacterium – name Lugdunin – which is so powerful it can even kill antibiotic resistant strains of Staphyloccus aureus (Staph).

We also looked into ongoing research projects. Here’s a glimpse into what is happening in the lab and in the field on overcoming antibiotic resistance now:

Checking on the state of superbugs in sewage

To find new antibiotic treatments you need to understand the current state of resistance in different environments and populations. For Carl Johan Svensson that meant traveling to Nairobi, Kenya to collect human fecal samples in the city's sewage plant. These samples tell him which drug resistant bacteria can be found in the area, and how widespread they are. This work will help researchers develop early detection and response plans.

CRISPR turns a bacterium’s immune response against itself

Xavier Duportet, and his team at Eligo Bioscience are using genetically modified viruses to get resistant bacteria to kill itself. These viruses, called bacteriophage, are edited to carry the CRISPR/Cas9 system into the bacteria. Once inside, Cas9 cuts the target bacteria’s DNA at a designated spot causing the bacteria to self-destruct.

Tracking a growing number of drug-resistant bloodstream infections in Malawi

Bloodstream infections are a leading cause of death in sub-Saharan Africa. The region’s high rates of HIV, malaria, and malnutrition only exacerbate the situation. In this study, researchers monitored a large hospital in Malawi from 1998 to 2016 and found that while the number of bloodstream infections was in decline, there was a rapid expansion in the number of drug-resistant pathogens. These resistant pathogens are effectively untreatable because of limited local resources.

Featured image: Staphylococcus aureus. Courtesy of Eric Erbe and Christopher Pooley.