Persistent Bacterial Infections: Molecular Mechanisms, Diagnostic Advances, and Preventive Strategies

Abstract Persistent bacterial infections pose a critical challenge to global healthcare. Unlike their acute counterparts, persistent infections exhibit a prolonged, recurrent clinical course and marked recalcitrance to standard antibiotic therapies, driven by the bacterial capacity to transition into metabolic dormancy (persistence). This review synthesizes current insights into the molecular mechanisms governing persistence, evaluates cutting-edge diagnostic modalities for persister detection, and outlines promising eradication strategies. We delineate the pivotal pathways driving persister formation, focusing on type II toxin-antitoxin modules (e.g., MazEF, HipAB) and global stress response networks (the SOS response and RpoS regulon). Furthermore, we highlight how persisters actively evade host immunity via peptidoglycan remodeling and the induction of arginase-1, which depletes local L-arginine pools and suppresses T-cell functions. We systematically review emerging diagnostic platforms—spanning molecular, metabolic, immunological, microfluidic, and phage-mediated technologies—and address the clinical threat of convergent lineages, exemplified by hypervirulent and multidrug-resistant Klebsiella pneumoniae.