New approaches for disabling biofilm development; identification and characterization of novel natural products that may have therapeutic utility. 

The increased incidence of antibiotic-resistant bacteria has renewed interest in discovering new bactericidal agents that operate with novel mechanisms. The Kolter lab is employing a variety of techniques and approaches to gain insights into natural products that may have therapeutic utility, particularly against increasingly virulent drug-resistant bacteria. Especially important is the lab’s work on the nonribosomal peptide synthetases and polyketide synthases, which generate various chemical species with therapeutic potential. The lab’s interest in the key cellular and biochemical aspects of biofilm development also has clinical ramifications because bacteria, such as Listeria monocytogenes and Pseudomonas aeruginosa, can cause serious infections, including Listeriosis, nosocomial, and opportunistic infections. Companies interested in developing novel anti-bacterial therapies have a unique opportunity to explore new avenues for therapeutic development by partnering with Dr. Kolter.
 

The Kolter lab is investigating the biological mechanisms that determine the structure and group dynamics of biofilms. It continues to work on bacterial gene expression and genomic studies. The lab also explores natural products in the context of their natural settings, rather than simply screening them for activity against disease targets. To complement these natural product studies, the lab uses a variety of genetic approaches, such as isolating mutants, to gain functional insights. The lab is also focused on developing simple and robust high-throughput screens, including fluorescence-based assays that detect the presence of a metabolite of interest.

• Explore the complex biological mechanisms that produce biofilms, including the critical roles played by extracellular matrix formation.
   
• Investigate bacterial genetics and physiology, highlighting various biochemical pathways and their corresponding genes, as well as the functions of previously uncharacterized natural products.
   
•  Develop improved detection methods for natural products of interest.

Dr. Kolter’s laboratory studies bacterial genomics, biofilms, and microbial ecological processes. Biofilms are complex meshworks of bacterial species connected by an extracellular matrix. The laboratory has performed and published extensive biofilms analyses. Biofilms can grow on many surface types  and as a result of their community organization, the cells’ properties change, including increases in their antibiotic resistance. In a recent article, the lab described how it uncovered cellular differentiation of Bacillus subtillis within the biofilm and how it found that extracellular matrix formation and bacterial development of a proper biofilm network are prerequisites for sporulation. Other studies have focused on the phenomenon of quorum sensing, a process of collective gene expression synchronization in biofilms. The lab’s data demonstrated a connection between quorum sensing and the expression of a particular operon in Pseudomonas aeruginosa that encodes proteins needed for the production of sugar-containing, extracellular, matrix constituents. The lab was the first to demonstrate this connection in biofilms.

In other studies, the lab has worked with various Listeria monocytogenes mutants to uncover the important role of flagella-driven bacterial motility in proper biofilm formation. It has analyzed the genes that encode a large protein conglomerate comprised of nonribosomal peptide synthetases and polyketide synthases, which have been exploited for therapeutic potential.   
 

Biological Mechanisms and Pathways

• Bacterial extracellular matrix •
• Biofilm •
• Intercellular signaling •
• Interspecies interactions •
• Microbial ecology •
• Microbial genomics •
• Non-ribosomal peptide synthesis •
• Quorum sensing •
• Sporulation
•  

Disease Mechanisms

• Cystic fibrosis lung infection •
• Microorganism
•  

Research Tools and Instrumentation

• Microorganism •
• Natural products
•  

Therapeutics

• Natural products
•