Listeria monocytogenes PdeE, a phosphodiesterase that contributes to virulence and has hydrolytic activity against cyclic mononucleotides and cyclic dinucleotides

Authors: REDDY, S - Mississippi State University; TURAGA, G - Mississippi State University; ABDELHAMED, H - Mississippi State University; BANES, M - Mississippi State University; WILLS, R - Mississippi State University; LAWRENCE, M - Mississippi State University

Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/11/2017
Publication Date: 7/12/2017
Citation: Reddy, S., Turaga, G., Abdelhamed, H., Banes, M.M., Wills, R.W., Lawrence, M.L. 2017. Listeria monocytogenes PdeE, a phosphodiesterase that contributes to virulence and has hydrolytic activity against cyclic mononucleotides and cyclic dinucleotides. Microbial Pathogenesis. 110:399-408.

Interpretive Summary: Listeria monocytogenes is an important foodborne pathogen, and novel means to control infection are needed. We discovered a Listeria monocytogenes enzyme involved in controlling its ability to cause disease. The enzyme is a phosphodiesterase, and its activity is to cleave cyclic dinucleotides, which are bacterial signal molecules used to control gene expression. Other listerial phosphodiesterases have been discovered previously, but the one we described is novel because it is able to cleave several types of cyclic dinucleotides. Previously discovered listerial phosphodiesterases are very specific for cleaving only a specific type of cyclic dinucleotide. Our discovery of this novel enzyme type may allow development of improved control measures for listeriosis.

Technical Abstract: We have identified and partially characterized a putative HD domain hydrolase, LMOf2365_2464, which is highly expressed during listerial intracellular replication. LMOf2365_2464 is annotated as a putative HD domain-containing hydrolase. The ability of an isogenic mutant strain, F2365'2464, to adhere, invade and replicate in intestinal epithelial cells (Caco-2) was significantly lower than parent strain F2365. Colonization of mouse liver and spleen by L. monocytogenes F2365 was significantly higher than it was for the mutant. The recombinant protein showed phosphodiesterase activity in the presence of divalent metal ions, indicating its role in nucleotide metabolism. It has activity against several cyclic nucleotides and cyclic dinucleotides, but its strongest activity is against cyclic di-AMP and cyclic AMP. Based on this enzymatic activity, we designated LMOf2365_2464 phosphodiesterase E (PdeE).