Dr. Anna Konovalova
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Microbiology and Molecular Genetics
Gram-negative bacteria have an outer membrane (OM) that surrounds and protects the cell from harmful chemicals, including antibiotics and host factors. Our immune system produces cationic antimicrobial peptides (CAMPs) that destabilize the OM by targeting the surface glycolipid called lipopolysaccharide (LPS). Bacteria, in turn, have evolved an Rcs envelope stress response to reinforce their membrane when antimicrobial peptides are present.
My current work focused on the sensory component of this stress response, a lipoprotein RcsF. For a long time, it was not clear how the bacteria sensed the presence of the CAMPs, because LPS is found exclusively in the outer leaflet of the OM, while RcsF was believed to be tethered to the inner leaflet of the OM facing the periplasm instead of the cell surface. We have discovered that the RcsF is threaded through barrel-shaped proteins, called OMPs, to expose an N-terminal domain on the cell surface. We have isolated several mutants of Escherichia coli that still make RcsF but unable to localize it to the cell surface due to the defects in the assembly of the RcsF/OMP complexes. We showed that these mutants are essentially “blind” to the presence of antimicrobial peptides, and proving that it is the surface-exposed domain that works as the sensor. We want to understand how RcsF monitors integrity of the LPS layer and how RcsF transduces the information across the OM to the downstream components.
It was a long-held view that the OM lipoproteins always faced the interior of the cell, specifically the compartment between the OM and the cytoplasmic membrane, called the periplasm. However, recent work, including my own on the lipoprotein RcsF, has revealed the presence of lipoproteins on the cell surface. My research is also focused on how lipoproteins localize to the cell surface and what the role they play in bacterial physiology and host-microbe interactions.