Molecular mimicry and functional convergence of bacterial proteins in host-microbe interactions.

Bacterial proteins modulate host immunity through diverse molecular strategies that are often broadly described as molecular mimicry. However, inconsistent terminology has obscured distinctions between genuine host-like interactions and other forms of host-directed immune modulation. We propose an operational framework that classifies bacterial proteins into four mechanistic categories: molecular mimicry, mimic-like behavior, functional convergence, and pathway interference. The framework prioritizes explicit criteria, including host-target engagement, interaction-interface similarity, functional equivalence, predominant molecular mechanism, and strength of supporting evidence, rather than immune outcome alone. Representative bacterial effectors are discussed alongside their evolutionary origins, computational prediction, experimental validation, and emerging technologies for mechanistic investigation. By separating evolutionary processes from molecular action and applying evidence-based classification criteria, this review clarifies ambiguous terminology and provides a consistent conceptual foundation for interpreting bacterial immune modulation. The framework may also guide future mechanistic studies, comparative analyses, and translational research across diverse pathogenic and commensal host-microbe interaction systems.