Antibiotic resistance poses a great challenge in treatment of serious bacterial infections, but development of therapies that could replace antibiotics in such severe cases has had limited success. In a new PLOS Biology study, Kristofer Wollein Waldetoft and Sam Brown from Atlanta’s Georgia Institute of Technology reviewed previous studies of antibiotic use. They aimed to determine which infections drive the evolution of antibiotic resistance and could be targets for development of alternative therapies.
I interviewed Wollein Waldetoft via email to find out more.
What led you to study bacteria, and what do you find so interesting about them?
KWW: As a student, I came into contact with two professors working on how and why bacteria cause disease: Lars Björck, whose focus was molecular mechanisms, and Lars Råberg, who worked on evolution. The interface between these two fields was intriguing. My continued interest in bacteria mainly stems from their impact on human health.
Many scientists worry that antibiotic resistance could spread to render our existing therapies useless. What would a world without antibiotics look like?
KWW: Losing antibiotics would not exactly take us back to the Middle Ages, because there have been other improvements since then, but we’d expect it to increase deaths from infectious diseases. Important medical interventions such as cancer chemotherapy, surgery, and care of premature babies would be riskier or even impossible. It is a dire prospect.
In this study, you used an evolutionary approach to analyze data on antibiotic use – what question were you addressing?
KWW: Alternative therapeutics could help save lives in two different ways. Firstly, they could treat deadly infections when bacteria have become resistant to antibiotics. This has proven difficult, because deadly infections put high demands on therapeutics. Secondly, alternative therapeutics could replace antibiotics in treating the infections that drive the evolution of antibiotic resistance. Antibiotics could then be saved for those who really need them. So the evolutionary question is, which infections drive the evolution of antibiotic resistance?
What did you discover?
KWW: We found that mild infections make a large contribution to antibiotic use, and it is plausible that this has a large impact on resistance evolution. Fortunately, this means that much may be gained from developing alternative therapeutics for infections that are mild enough to be feasible targets.
What alternative therapies could be used to combat mild infections, if antibiotics were saved for the more severe cases?
KWW: Approaches that have been discussed lately include targeting microbial molecules known as virulence factors, which cause harm to the host, or disrupting the microbes’ communication systems.
What do you hope your study might lead to?
KWW: We hope to contribute to a broader discussion on the development of alternatives to antibiotics. Since these alternative therapies are often less effective than antibiotics in treating deadly infections, their development risks being sidelined. We hope that by flagging their potential role as “junior partners” in a treatment spectrum from mild to severe cases, we can promote their continued development, preserving effective antibiotics for life-threatening cases in future.
Research Article: Wollein Waldetoft K, Brown SP (2017) Alternative therapeutics for self-limiting infections—An indirect approach to the antibiotic resistance challenge. PLoS Biol 15(12): e2003533. https://doi.org/10.1371/journal.pbio.2003533
Images Credits: oliver.dodd, Flickr; Kristofer Wollein Waldetoft