Washington, Dec 8: A new research has led to the identification of a previously unknown mechanism that pathogens use to sabotage the host immune system.

The mechanism works by encouraging pathogenicity through manipulation of a common signaling pathway in host cells.

The research finds significant implications for the food industry and for the development of new antibiotics.

The results of the study may also tell if mammalian cells can utilize a similar mechanism for potentially permanent and irreversible posttranslational modifications.

The study was led by Dr. Feng Shao from the National Institute of Biological Sciences, Beijing.

Specialized mechanisms for disrupting the ability of host cells in order to activate innate immune responses that providing immediate defense against infection, have been evolved in many gram negative bacteria.

Mitogen-activated protein kinase (MAPK) pathways play key roles in activating host innate immune responses and are frequent targets of pathogenic effectors in both plants and animal systems.

All MAPKs have a threonine -X-tyrosine motif and need phosphorylation of both threonine and tyrosine for activation.

Earlier work established that members of the OspF family, including OspF from Shigella and SpvC from Salmonella, are phosphothreonine lyases that promote pathogenicity by directly targeting and irreversibly inhibiting the activation of MAPKs.

The researchers used mass spectrometry to examine the mechanism responsible for the inactivation of MAPKs by the OspF family of effectors.

Dr. Shao’s team had identified the crystal structure of SpvC and its complex with a phosphopeptide substrate.

This enzyme-substrate complex revealed how SpvC ties up with activated MAPK through identifying the phosphotyrosine and then manages the phosphothreonine into the enzyme active site.

The data suggested that MAPK p38 is the preferred substrate for OspF and SpvC during bacterial infection as it has the required conformational flexibility for such interaction.

The researchers identified in the process that a previously unknown catalytic mechanism of acid-base mediated "-elimination of phosphoserine/phosphothreonine that irreversibly inactivated the kinase.

“Our data provide biochemical and structural evidence for specific recognition of the dual phosphorylated MAPK substrates by the OspF family of phosphothreonine lyases and explain the enzyme’s differential activities towards different MAPK substrates, ” explained Dr. Shao.

In addition, as phosphorylation of serine and threonine residues is extensively used as a regulatory mechanism in mammalian cells, the researchers contemplated that phosphoserine or phosphothreonine lyases might be present in eukaryotes and serve as post-translational modification enzymes that irreversible dephosphorylate kinases or other phosphorylated substrates.

The research was published by Cell Press in an issue of Molecular Cell. (ANI)