# Ribosomal Hiberation Factor Links Quorum-Sensing to Acid Resistance in EHEC
## 1 Introduction  
Enterohernorrhagic _Escherichia coli_ (EHEC), particularly serotype O157:H7, poses a severe global threat to public health, largely due to its capacity to cause devastating foodborne illness [1]. Successful host colonization critically depends on the pathogen's ability to withstand the extreme acidic barrier of the human stomach [2]. Consequently, sophisticated acid resistance (AR) mechanisms are indispensable virulence factors, enabling survival during gastric transit [3]. Although major AR systems such as the glutamate-dependent gad pathway and chaperones like HdeA have been identified, the molecular orchestrators conferring rapid, inducible protection under the dynamic and harsh conditions encountered in vivo remain inadequately defined [4]. Understanding the environmental cues sensed by the pathogens and how they regulate integrated protective responses represents a significant gap in our knowledge of enteric pathogenesis. Quorum sensing (QS), a cell-density-dependent communication system, regulates collective behaviors essential for bacterial adaptation and virulence across diversepathogens [5]. In EHEC, which lacks its own AHL synthase, the LuxR homolog SdiA detects exogenous acyl-homoserine lactones (AHLs) produced by other gut microbiota members [6; 7; 8]. However, a critical unanswered question persists: what downstream effector mechanism(s) link SdiA-mediated QS signal reception directly to the robust activation of AR [5]? Elucidating how EHEC harnesses microbiome-derived QS signals to mount its own life-saving defenses is crucial for deciphering its persistence strategies and identifying potential therapeutic targets. The molecular executor(s) connecting SdiA activation to enhanced AR, and their possible integration with core stress regulators like RpoS [9; 10; 11; 12], remain fundamental unresolved aspects of enteric pathogen adaptation physiology. While stress transcriptomics in EHEC often implicate ribosomal gene expression changes, the specific functional contribution of ribosomal dynamics--particularly under lethal acidity--is poorly understood [13; 14; 15]. Research has primarily focused on established AR genes (_gadA_, _hdeA_) [5], yet these systems alone cannot consistently explain the profound resilience observed during severe acid shock or its interplay with concurrent stressors. The significant survival enhancement conferred by exogenous AHLs strongly suggests a functional QS-AR linkage in EHEC [16], but the specific mechanism--how SdiA-AHL sensing translates into cytoprotective physiology--has eluded definition. What is the essential effector pathway downstream of QS? Growing evidence implicates ribosomal hibernation, an energy-conserving strategy mediated by factors like Ribosome Modulation Factor (RMF) and RaiA, resulting in translationally inactive 100S ribosomes, in stress adaptation beyond simple nutrient deprivation [13; 14; 15; 17; 18; 19; 20]. While stress transcriptomes frequently highlight ribosomal pathways, their definitive role in critical virulence adaptations, particularly acid resistance, is largely speculative. Does QS signaling via SdiA specifically induce ribosomal hibernation as a core survival strategy [5; 7; 8]? Is this ribosomal reprogramming strictly required for QS-mediated AR, and does it functionally intersect with known AR machinery or the master stress regulator RpoS [9; 12]? Moreover, how is this potential pathway regulated by the environmental signal itself--namely, the rapid shift to low pH? Resolving these mechanistic questions is essential to define the hierarchy and integration points within EHEC's sophisticated adaptive network. This study aimed to elucidate the molecular mechanism by which QS confers acid resistance in EHEC, with a specific focus on the role of ribosomal hibernation and its master regulator RMF.