Rewiring of cell morphology by Small protein B enhances stress tolerance and colonization in Aeromonas veronii under adverse conditions

Pathogens often display morphological plasticity to withstand environmental stress and thrive in complex host immune environments. In this study, we demonstrated the morphological adaptation of Aeromonas veronii, a severe pathogen with a wide environmental distribution. Our results establish the critical role of Small protein B (SmpB) in morphological adaptation and reveal a conserved dual-safety regulatory mechanism mediated by ArgR. A. veronii exhibited morphological changes and gained enhanced stress resistance in response to environmental cues. We identified the trans-translation component SmpB as critical for this morphological adaptation, independent of its canonical role in trans-translation. Furthermore, SmpB transcriptionally up-regulates peptidoglycan biosynthesis genes. A convolutional neural network model predicted ArgR as a transcriptional regulator of smpB. Subsequent biochemical assays confirmed that ArgR directly bound to the smpB promoter and repressed its transcription by sequestering RNA polymerase. Moreover, the interaction between ArgR and SmpB promoted the affinity of ArgR for the smpB promoter. SmpB-mediated morphological rewiring enhanced A. veronii’s intestinal colonization and virulence in a mouse infection model. Collectively, our study reveals a novel mechanism in which SmpB, operating in a negative feedback loop with ArgR, modulates cell wall synthesis and enhances bacterial ecological fitness. These insights into host–pathogen interactions identify promising targets for innovative antimicrobial therapies and diagnostic strategies.