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The Bac-SMART Group (Bacterial Stress Modulation and Antimicrobial Resistance/Tolerance) decodes how bacteria use stress responses to resist antibiotics and phages. We develop novel strategies and therapeutic targets to combat persistent, untreatable infections (by e.g., CRE, XDR-Shigella).
Research focus
Research focus
Our lab investigates how bacterial stress response pathways – governed by second messengers (e.g., (p)ppGpp, cyclic AMP) and two-component systems – enable survival under antibiotic treatment and phage predation. These pathways are fundamental drivers of antimicrobial tolerance, persistence, resistance, and the evolutionary dynamics of phage-bacteria interactions.
To study these systems, we combine molecular and biochemical techniques, systems biology, omics, structural tools (including crystallography, protein design), biophysics, and infection models (including animal studies) to dissect the mechanisms linking stress signaling to treatment failure. Through close international collaborations, we aim to reveal mechanistic insights and translate them into novel strategies to combat persistent and untreatable bacterial infections.
Current research areas
Current research areas
1. Stringent Response (SR) Pathway & Bacterial Stress Adaptation
We investigate how the universal alarmone ppGpp reprograms bacterial metabolism and physiology to survive stresses (e.g., nutrient starvation, antibiotics, virulence challenges). Key focuses include:
ppGpp Homeostasis: Molecular regulation of RelA/SpoT enzymes that synthesize/degrade ppGpp in response to environmental cues.
ppGpp Targets1,6,8,9: Mechanistic studies of ppGpp interactions with conserved cellular targets (e.g., PpnN-mediated metabolic balancing during stress).
Phenotypic Outcomes: Linking ppGpp dynamics to antibiotic persistence8, resistance evolution5, and infection outcomes7.
Single-Cell Heterogeneity5: How ppGpp-driven cell-to-cell variation enables bacterial survival under stress?
2. Phage-Bacteria Interactions & Evolutionary Arms Races2
We dissect molecular mechanisms governing phage infection under stresses, including:
Host Hijacking: Identification of key bacterial/phage proteins enabling invasion (e.g., SR and anti-SR systems).
Stress-Driven Coevolution: How bacterial resistance mutations (e.g., surface modification) and phage counter-adaptations shape long-term evolutionary dynamics.
Persistent Infection Strategies: Phage exploitation of bacterial dormancy/persistence states for survival.
3. Translational Applications
Leveraging SR (,etc) and phage-host insights to develop:
Novel Antimicrobials: Targeting ppGpp networks3 to combat multidrug-resistant infections.
Phage-Based Solutions: Precision biocontrol agents for agriculture and engineered therapies against persistent pathogens.
Key words: stringent response, ppGpp, antibiotic tolerance, persistence, resistance, second messenger, phage-host interaction, phage therapy
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