Engineering Phage to Lyse Cells as a Result of Bacterial QS in ESKAPEE Pathogens
The rise of antibiotic-resistant pathogens is a significant public health threat, particularly in built environments such as hospitals. ESKAPEE pathogens – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli – are among the most dangerous, being highly linked to deaths associated with antibiotic resistance. These pathogens can form biofilms, which shield them from treatments and contribute to their persistence, especially in nutrient-rich, hard-to-clean environments like sink drains.
This project aims to engineer bacteriophages (phages) that respond to bacterial quorum-sensing (QS) signals called autoinducers (AI) – chemical messages that bacteria use to coordinate collective behaviors, including biofilm formation. By designing phages to detect these signals, we expect to induce targeted bacterial lysis, breaking down biofilms and preventing their spread. We use bioinformatic and comparative genomic analyses to identify key QS systems in ESKAPEE pathogens found in built environments. Then, through synthetic genomics, we will modify phages to express QS signal receptors, enabling them to lyse bacteria when AIs are detected.
Top Figure: Host AI-induced phage lysis.
Researchers
- Crissy Massimino
Funding
Collaborators
Microbial Life in Plastic? Fantastic! Profiling Microbial Communities in Long-Term Plastisphere Microcosms for Bioremediation Application
Microplastics—polymers found or manufactured as microscopic particles or shed from larger commercial plastic products— are everywhere, persistent, and leach chemically active compounds that affect the surrounding environment. Additives incorporated into polymers during production (e.g., for functional benefit such as pigment, solvent, durability, etc.) have measurable effects on biota, including toxic effects in humans. Microplastic leachates also affect microorganism cellular processes, and impacts vary by polymer and additive composition and taxa. Bioengineering microbes for plastic degradation is a developing plastic pollution remediation strategy that enlists microbes to produce enzymes that break down persistent polymers.
Non-specific batch cultures (donated by Dr. Anna Villalobos Santeli) were grown for two years on microplastics of various polymer composition with constant thermal and physical perturbation and no external nutrients to encourage niche adaptation and enrich for organisms evolved to thrive on plastic and plastic leachate. This project aims to investigate these cultures to (1) examine the effect of heat, shaking, and microbial colonization on microplastic surface topology, (2) identify prime degraders of plastic and plastic leachate, and (3) characterize their genomes to find key operons involved in plastic degradation. This study is being conducted in collaboration with the Bioremediation of Plastic Pollution to Conserve Biodiversity Bass Connections Group that is bioengineering microbes for plastic degradation. This work will illuminate how microbes interact with microplastics and their erosion products and has the potential to identify key species and genes to fuel ongoing plastic bioremediation efforts.
Researchers
- Natalia Melbard
- Lan Nguyen