Insights into calcium transport in Listeria pave way for new antibiotics and food safety solutions

Calcium ions play a vital role as cellular messengers across all living organisms, from plants to humans, regulating processes like heartbeats and stress responses. Disruptions in calcium levels can cause severe health issues, such as heart failure. While past research has primarily focused on calcium transport in eukaryotic systems, this study shifts the focus to bacterial systems, by using biophysical tecniques, such as cryo-electron microscopy (cryo-EM) and time-resolved X-ray solution scattering (TR-XSS) at the ESRF.

The team explored calcium transport mechanisms in Listeria monocytogenes, a bacterium known for contaminating food and posing health risks, particularly to pregnant women and young children. Listeria is notoriously resistant to hostile environments much due to a calcium-transporting protein called LMCA1, enabling it to survive in alkaline conditions, such as in food processing solutions and within the immune system. Alkaline pH environments, whether in food processing or the body's defense mechanisms, allow Listeria to persist rather than to be eliminated.

Potential antibiotic and food applications

“We chose LMCA1 as a target for this study because it has potential for antibiotic development and food industry applications,” said Magnus Andersson, team leader at Umeå University and the paper’s corresponding author.

The team used cryo-EM in Sweden to show how a single calcium ion is bound inside LMCA1 on its way across the bacterial membrane. While the scientific community had known about this transport process, the specific details of ion binding had remained unclear until now.

The study also used a time-resolved X-ray scattering technique at beamline ID09 at the ESRF to track calcium transport in real time and identified a mechanism that minimizes the bacterium's exposure to external threats. One key finding from the ESRF experiments was that phosphorylation of LMCA1 governs the speed of calcium transport, an adaptation evolved to protect bacteria from environmental hazards. This mechanism differs from calcium transport in higher organisms.

Setting up this complex time-resolved experiment required extensive beamtime. “The work at the ESRF allowed us to directly track calcium transport in real time without introducing labels, an otherwise impossible task,” said Andersson.

The team's success has led to funding from the National Institute of Health for a collaborative project with the University of Michigan. Their new research will focus on calcium transporters in the human heart, aiming to develop activators to combat heart failure. “Thanks to our success with Listeria, we can now apply the same methods to this new study,” concluded Andersson.

Reference:

Prabudiansyah I. , Science Advances, Vol 10, Issue 41, 11 Oct 2024. DOI: 10.1126/sciadv.adp291

Text by Montserrat Capellas Espuny

Top image: the calcium-binding structure of LMCA1 inserted into a membrane environment and a zoom-in on the binding site. Credits: M. Andersson