Office: ISA 6209
- Website: https://sites.google.com/view/bobrovskyy-lab
- Google scholar: https://scholar.google.com/citations?hl=en&user=bAuSBzcAAAAJ
- Twitter: https://twitter.com/Bobrovskyy_Lab
- B.S. Molecular and Cellular Biology, University of Illinois at Urbana-Champaign
- Ph.D. Microbiology, University of Illinois at Urbana-Champaign
- Postdoctoral Fellow, The University of Chicago
Type 7 secretion system of methicillin-resistant Staphylococcus aureus (MRSA).
Bacteria actively secrete protein factors to manipulate and evade host immune defenses or compete with other microbes for resources. Bacteria employ the general secretion (Sec) and Twin-arginine translocation (Tat) pathways to support translocation of proteins containing an N-terminal cleavable signal peptide across the plasma membrane. Many clinically important pathogens of the Firmicute and Actinobacteria phyla, such as Mycobacterium tuberculosis, Streptococcus agalactiae, Bacillus cereus, and Staphylococcus aureus, encode a specialized Type 7 Secretion System (T7SS) that supports translocation of diverse effector proteins and polymorphic toxins across the bacterial envelope. These proteins implement specific virulence strategies or antagonize competitor organisms. In S. aureus, T7SS proteins are encoded by a cluster of genes referred to as ess locus. EssC, a conserved FtsK/SpoIIIE ATPase together with EsaA, EssA and EssB, assemble in the bacterial envelope into a T7SS translocon to support the transport of small substrates EsxA-D (WXG family), as well as the larger effector proteins EssD and TspA (polymorphic toxins of the LXG family). The mechanisms allowing T7SS translocon assembly into the cytosolic membrane and across the thick peptidoglycan layer to support protein secretion, as well as the contribution of effector proteins to S. aureus virulence and/or bacterial competition have not been fully elucidated and are the subject of our research in the Bobrovskyy lab.
Peptidoglycan remodeling in staphylococcal protein secretion and cell cycle.
Gram-positive bacteria and their cytosolic contents are protected from the outside environment by a cell envelope consisting of an inner membrane and a thick cell wall. Staphylococcal cell wall is a 20-30 nm thick structure comprised of peptidoglycan (PG), a macromolecule that forms a mesh to provide rigidity and protect the cell from osmotic lysis. PG also serves as an anchoring scaffold for capsular polysaccharide, teichoic acid and polypeptides which are displayed on the bacterial surface, and is involved in the protein secretion and cell division processes. Due to its essential functions, PG homeostasis has to be constantly maintained through the coordination of peptidoglycan synthesis and hydrolysis. Several families of antibiotics target this fine-tuned balance to cause growth inhibition or death. Recently, we characterized EssH, a peptidoglycan hydrolase required to support secretion via T7SS. EssH bears a peptidoglycan hydrolytic CHAP domain also present in at least ten other proteins conserved amongst various S. aureus strains. We are interested in understanding 1) the mechanism whereby EssH supports T7-dependent secretion, and 2) the role of the conserved CHAP domain proteins in secretion and cell cycle.