A new study by Australian researchers has revealed how the bacterium Streptococcus pneumoniae (pneumococcus) obtains the essential nutrient manganese from our bodies, which could lead to better therapies to target the life-threatening, antibiotic-resistant pathogen.

The findings of the study were published in the journal Science Advances. Pneumococcus is one of the world's deadliest organisms, responsible for more than one million deaths each year and is the leading infectious cause of mortality in children under five. It is the main cause of bacterial pneumonia, as well as a major cause of meningitis, sepsis and inner ear infections (otitis media).

After ten years of detailed investigations, researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Bio21 Molecular Science and Biotechnology Institute (Bio21), along with collaborators at the Australian National University and Kyoto University, Japan, have determined the structure of the unique 'gateway' that pneumococcus uses to steal manganese from the body.

All organisms, including pathogens, need vitamins and minerals to survive. While researchers knew that manganese was critical for the survival of the pneumococcus, how it took manganese from the body wasn't understood.
University of Melbourne Associate Professor Megan Maher, a laboratory head at Bio21, said they noticed the bacterium was drawing in nutrients in a regulated way.

"Eventually we discovered that this was due to a unique gateway that sits in the bacterium's membrane that opens and closes to specifically allow manganese in," said Associate Professor Maher. "This is a completely new structure that has never been seen in a pathogen like this," added Professor Maher.

University of Melbourne Professor Christopher McDevitt, a laboratory head at the Doherty Institute, said the study's finding changes what we know about the pathogen's survival. "Previously, it was thought that these gateways acted like Teflon coated channels in the sense that everything just flowed through," said Professor McDevitt. "Now we understand that it is selectively drawing the manganese in. Any disturbance of this gateway starves the pathogen of manganese, which prevents it from being able to cause disease," explained Professor McDevitt.

It could hold the key to better and alternative therapies against pneumococcus. Although a pneumococcal vaccine does exist, it only provides limited protection against circulating strains, and antibiotic resistance rates are rapidly rising. "It's a really attractive therapeutic target as it sits on the surface of the bacterium, and our bodies don't use this type of gateway," said Professor McDevitt. "At a time when we are seeing rising resistance to our first and last line antibiotics, and the emergence of 'superbugs', it is important that we think of new strategies to control this deadly organism," concluded Professor McDevitt.