Starving pneumonia-causing bacteria of its favorite 'food' holds promise for new antibiotics

The structure includes the transmembrane areas in blue, energy driving domains and membrane lipids in pink. The position of the gating residues within the pathway is represented by the yellow 'blobs. Credit: Hugo MacDermott Opeskin, Megan O'Mara, and Christopher McDevittAustralian researchers have shown how Streptococcus pneumoniae (pneumococcus), obtains the essential nutrient manganese from our bodies. This could help us develop better treatments to combat this life-threatening, antibiotic resistant pathogen.Pneumococcus, one of the most deadly organisms in the world, is responsible for over one million deaths annually and is the leading cause of death among children younger than five years old. It is the leading cause of bacterial pneumonia and a major contributor to meningitis, sepsis, and inner ear infections (otitis media).Today's Science Advances article was published after ten years' of research by researchers from the Peter Doherty Institute for Infection and Immunity and the Bio21 Molecular Science & Biotechnology Institute. They have also collaborated with colleagues at Kyoto University, Japan and Australian National University to determine the unique structure of the 'gateway" that pneumococcus uses for stealing manganese from the body.Vitamins and minerals are essential for all organisms, even pathogens. Although researchers understood that the survival of the pneumococcus was dependent on manganese, it wasn't clear how the body got its manganese.Megan Maher, an Associate at the University of Melbourne, stated that they noticed that the bacterium was drawing nutrients in a controlled way.Associate Professor Maher said, "Eventually we discovered this was due to an unique gateway that sits within the bacterium membrane that opens to specifically allow manganese into.""This is a totally new structure that has never before been seen in a disease like this."Christopher McDevitt from the University of Melbourne, who is a laboratory director at the Doherty Institute said that the findings of the study change what we know about the survival of the pathogen.Professor McDevitt explained that previously, it was believed that these gateways were like Teflon-coated channels and that everything flowed through them.We now know that the gateway selectively draws in manganese. Any disruption of this gateway causes the pathogen manganese to become starved, which makes it less likely to cause disease.This could be the key to alternative treatments for the pneumococcus.A pneumococcal vaccine is available, but it does not provide protection against all circulating strains. Antibiotic resistance rates are quickly rising.Professor McDevitt stated, "It's an attractive therapeutic target because it sits on top of the bacterium. Our bodies don't use that type of gateway.""At a moment when we are witnessing rising resistance to our last and first line antibiotics, as well as the emergence of superbugs' it is important to think of new strategies for controlling this deadly organism."Continue reading Asymptomatic adults could be reservoirs for Streptococcus pneumoniaeScience Advances (2021): More information Information from Science Advances: The structural basis for bacterial manganese import, (2021). DOI: 10.1126/sciadv.abg3980