Researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Bio21 Molecular Science & Biotechnology Institute (Bio21), along with collaborators at the Australian National University and Kyoto University, Japan, have revealed how the bacterium Streptococcus pneumoniae obtains manganese from our bodies. The findings can help lead to better therapies.
Their findings were published in the journal Science Advances in a paper titled, “The structural basis of bacterial manganese import.”
“Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway for many micronutrients including the first-row transition metal manganese,” wrote the researchers. “However, the structural features of ionic metal transporting ABC permeases have remained undefined. Here, we present the crystal structure of the manganese transporter PsaBC from Streptococcus pneumoniae in an open-inward conformation.”
Although researchers were aware that manganese was critical for survival of the pneumococcus, it was unclear how manganese was taken from the body.
“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,” explained Megan Maher, PhD, University of Melbourne associate professor and laboratory head at Bio21.
“This is a completely new structure that has never been seen in a pathogen like this.” The new findings change 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,” explained Christopher McDevitt, PhD, a University of Melbourne professor and laboratory head at the Doherty Institute.
“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.”
These new findings could pave the way for alternative therapies against the pneumococcus and combat increasing antibiotic resistance rates.
“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,” McDevitt said.
“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.”
