Biophysical Society Thematic Meeting

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

31-POS

Board 31

MgtA from E. Coli Show Strong Cardiolipin Dependent Activity and is Stimulated by Free

in the Sub Micromolar Range

Saranya Subramani, Harmonie Perdreau-Dahl,

Jens Preben Morth

Oslo University, Oslo, Norway.

Clusters of virulence genes, called pathogenicity islands, are incorporated into the genome of

pathogenic microorganisms. The clusters are normally absent in the non-pathogenic

microorganism of the related species. Pathogenicity islands containing genes associated with

bacterial pH and magnesium homeostasis have been shown to play a crucial role in bacterial

virulence, thus emphasizing the important role of magnesium and acidification of the local

environment during bacterial virulence and survival within the host cell.

The Magnesium transporter A (MgtA) is a specialized P-type ATPase important for with

magnesium import. The gene mgtA is upregulated when low magnesium levels or low pH in the

periplasmic space activate the two-component system PhoQ/PhoP. PhoQ/PhoP is linked with

virulence in most pathogenic bacteria. These studies demonstrate, for the first time, that MgtA is

highly sensitive to free magnesium levels in solution and follow a kinetic model that suggest

initial activation at sub micromolar levels by free magnesium (1-10 μM) followed by strong

substrate inhibition at elevated magnesium levels, already at 1 mM, indicating that MgtA may

act as a cytoplasmic magnesium sensor as well as a transporter. The activity of MgtA is highly

dependent on the presence of phosphatidylglycerols (PG) lipids and in particular cardiolipin.

Overexpressed MgtA in E. coli furthermore confirm that MgtA co-localize with the

cardiolipin/PG lipid rafts in the plasma membrane. In the presence of CL the dependencies

between ATP, free Magnesium and pH have been explored over a wide range. MgtA belongs to

the P3B –type ATPase subfamily that include members from eubacteria, archaea, fungi and

plants.