As therapies and antibiotics develop and improve, pathogens adapt to overcome current medications. Bacteria are a specific organism that can adapt quickly to resist antibiotic treatment due to rapid proliferation. As a result, over 2 million infections associated with bacteria occur annually in the United States. Some examples include drug-resistant pathogens such as Clostridioides difficile (C. diff), carbapenem-resistant Enterobacterales (CRE), and Mycobacterium tuberculosis (M. tb). These bacteria are known as superbugs that constitute a serious risk to humanity. To overcome these pathogens, stronger and more toxic treatments are necessary. However, scientists worry about developing stronger drugs due to bacteria’s ability to adapt to treatment. Scientists are working to understand more about bacteria to improve treatment efficacy and avoid drug resistant.
Scientists in Australia have recently developed a novel approach to target drug-resistant bacteria. The article published in Nature Chemical Biology, by the groups of Drs. Ethan D. Goddard-Borger and Richard J. Payne, designed antibodies that recognize sugar molecules on bacterial cells. This new treatment could lead to the development of multiple immunotherapies against hospital-acquired, drug-resistant bacteria. Goddard-Borger is a Professor at the Walter and Eliza Hall Institute of Medical Research (WEHI) where he works on glycoproteins and developing therapies using biochemical technology. Payne is a Professor and lead investigator at the University of Sydney. His research is focused on the design and synthesis of biomolecules to treat different diseases.
Both groups worked to demonstrate that laboratory-generated antibody has strong efficacy again bacterial infection in mice. The antibody was designed to recognize sugar molecules on bacteria, which direct the immune system toward the infection. This sugar molecule is known as pseudaminic acid (PA) and is produced by bacteria. PA is used by pathogens to escape host immune systems since its structure resembles sugars on human cells. However, since healthy human cells do not produce the same sugar, it is a good target that limits toxicity. Researchers were able to uncover the 3D structure and how it is presented on the outer membrane of bacteria.
To test the antibody, scientists turned to mouse models to see if it was effective in treating a drug-resistant bacteria known as Acinetobacter baumannii (A. baumannii). As a result, the novel antibody was able to respond to infection and eliminate infected cells. Researchers believe this drug can be used therapeutically and as a preventative treatment for hospital patients whom are more susceptible to infection. This form of therapy elicits protection known as passive immunity, which use antibodies to regulate and control infection as opposed to adaptive immunity, which requires immune cells to become activated. Since bacteria can evade immune cells, an antibody approach was necessary.
Goddard-Borger, Payne, and others have developed a therapy that combines biochemistry, immunology, microbiology, and infection biology. Consequently, a novel antibody has been designed that effectively targets drug-resistant bacteria. The team hopes to translate their drug and move it into the clinic. Firstly, they hope to target A. baumannii before extending their therapy to other types of bacteria. This paradigm-shifting work has the potential to set a new standard-of-care treatment to bacterial infections and marks a milestone in the race to overcome antimicrobial resistance.
Article, Nature Chemical Biology, Ethan D. Goddard-Borger, Richard J. Payne, WEHI, University of Sydney