Molecular Mimicry by Bacterial Effector Proteins

Microorganisms have developed sophisticated mechanisms to invade the host and evade the host's immune surveillance while exploiting the host's resources for their establishment through co-evolution. Many pathogens employ specialized protein secretion systems to transport virulence factors from the bacterial cytosol into host cells. These bacterial protein secretion systems can generally be categorized into different classes based on their structures, functions, and specificity. Notably, some pathogens have evolved proteins that mimic specific eukaryotic cell proteins, enabling them to manipulate host cellular pathways. This phenomenon is known as molecular mimicry. These proteins either closely resemble eukaryotic proteins or possess domains typically found in eukaryotes but generally absent in prokaryotes. This mimicry allows pathogens to interfere with host functions and facilitate their survival and proliferation within the host. Here, we review the fundamental characteristics of these secretion pathways, delve into the remarkable diversity of effector proteins, and explore the molecular mechanisms by which different pathogens rewire cellular pathways. Additionally, we discuss recent findings on strategies to counteract pathogen mimicry and the insights gained for the discovery of new antimicrobials.