Our lab studies how bacterial stress-response and nucleotide-signaling pathways shape survival under antibiotics and bacteriophage attack. A major emerging direction is to understand how host physiological states create replication-niche barriers, or host-state gates, that determine whether phage infection becomes productive, and how phages reprogram these states. By distinguishing dedicated bacterial immunity from physiology-dependent constraints on phage replication, we aim to uncover new principles of microbial survival and develop strategies against persistent and difficult-to-treat bacterial infections.
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 & Replication-Niche Barriers2
We dissect how bacterial physiological states influence phage infection and how phages encode proteins that reprogram these states. Key focuses include:
Phage reprogramming of host physiology: Identification of bacterial and phage proteins that control productive infection, including stringent-response and anti-stringent-response mechanisms.
Replication-niche barriers: How envelope stress, nucleotide signaling, metabolic state, and growth conditions determine whether bacteria are permissive or restrictive to phage replication.
Stress-driven coevolution: How bacterial resistance mutations and phage counter-adaptations shape long-term evolutionary dynamics.
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, nucleotide signaling, antibiotic tolerance, persistence, resistance, phage-host interaction, replication-niche barriers, host-state gates, phage replication permissiveness, phage therapy
Fundings