Speakers' Abstracts

Josephine (Josie) Chandler, Ph.D., Assistant Professor, Department of Molecular Biosciences, University of Kansas

"Making friends to make war: bacterial quorum sensing, cooperation and interspecies competition"

Our laboratory is interested in understanding how bacteria communicate and cooperate with each other to carry out complex group behaviors. We primarily study a cell-cell communication system in bacteria called quorum sensing. Most quorum sensing systems become activated when the bacterial population reaches a critical cell density (hence the term ‘quorum’ sensing). In many bacteria quorum sensing is important for pathogenesis but quorum sensing is also thought to be important for competition in mixed soil communities. Quorum sensing commonly controls production of extracellular factors, such as toxins, exoproteases, and components involved in self-structured biofilm-like communities. Production of extracellular factors often involves cooperation because the factors can be shared among all of the members of a population. Much is known about the molecular biology of quorum sensing, but our understanding of its role in promoting group or cooperative activities remains obscure. We use molecular genetic approaches and simple laboratory models to understand the selective forces that might lead to the evolution of quorum sensing and cooperation in bacteria in natural microbial communities. Our results may promote our ability to create, maintain and control cooperating bacterial communities, such as those involved in infections. In addition, bacteria serve as an excellent model for exploring the evolution of sociality in a broader context.


Mario Rivera, Ph.D, Professor, Department of Chemistry, University of Kansas

"Validating Iron Homeostasis as Target for the Discovery of Novel Antimicrobials

Antibiotic resistance is a worldwide problem, which threatens to disarm important procedures in modern medicine, such as cancer therapy, organ transplantation, etc. Pseudomonas aeruginosa, which is a significant source of hospital-acquired infections and the leading cause of mortality in patients with cystic fibrosis, is also notorious for its ability to develop a multidrug resistant phenotype. To combat antibiotic resistance new antibiotics and new targets are needed. We have been exploring a new direction in the development of antimicrobials, which targets iron homeostasis. Bacterial iron homeostasis offers a significant vulnerability because essential iron must be obtained from the host, but nutritional immunity makes the nutrient scarce to invading pathogens. Pathogens have evolved mechanisms to circumvent nutritional immunity and “steal” iron from their host, but these depend on well-regulated iron homeostasis. To disrupt bacterial iron homeostasis we are targeting the protein/protein interactions between the iron storage protein bacterioferritin (BfrB) and its associated ferredoxin (Bfd). The talk will summarize our efforts at understanding the structural biology of the BfrB/Bfd complex, the consequences of blocking the BfrB/Bfd interaction using genetic tools, and our strategies for developing small molecule inhibitors of the BfrB/Bfd interaction to disrupt iron metabolism in P. aeruginosa and render the opportunistic pathogen vulnerable.


Joanna Slusky, Ph.D., Assistant Professor, Department of Molecular Biosciences, University of Kansas

“Making antibiotic resistance futile: a new target for efflux pump inhibitors”

Antibiotic resistance is correlated with overexpression of the acridine efflux pump. This pump is the preeminent efflux pump in gram negative bacteria and is responsible for shuttling out most classes of antibiotics. Though efforts to disable pumps have focused on inhibiting one of the drug binding sites in the inner membrane component of the pump, those efforts have only yielded compounds that are toxic and overly specific. We are creating proteins that prevent oligomerization of the outer membrane component of the acridine pump. The outer membrane component of the acridine pump is a trimeric beta barrel called TolC. Targeting the outer membrane portion of the pump reduces concerns over toxicity because the target complex is in a structural class unique to bacterial outer membranes and human cells do not possess similar proteins. Moreover, targeting oligomerization of the pump instead of targeting one of the two binding sites of the pump broadens the applicability of the inhibitor. Specifically, by targeting oligomerization we can stop all efflux through the pump, not just the antibiotics that interact with one of the multiple acridine pump binding sites. Our long-term goal is to make drugs that will resensitize gram-negative antibiotic resistant bacteria to a variety of antibiotics.


Jeff Staudinger, Ph.D., Professor, Department of Pharmacology & Toxicology, University of Kansas

“BAG3 SUMOylation in Hepatocytes”

Covalent modification by SUMO is an important regulator of the functional properties of many proteins implicated in human diseases. While there are many examples of individual specific proteins regulated by SUMOylation, there has been no comprehensive survey of the targets of SUMOylation in a human disease. The major reason for this is the lack of a facile and general method for comprehensive identification and quantitating SUMOylated proteins in cells or live animal models. To resolve this problem, we genetically engineered two adenoviral expression vectors which encode a modified SUMO protein and the E3 SUMO-ligase enzyme-called Protein Inhibitor of Activated STAT-1 (PIAS1). Strong data indicate that Bcl2-associated Athanogene 3 (Bag3) is the molecular target of the inflammation-inducible PIAS1-mediated SUMO-signaling pathway, and that the biology of the Hsp70-Bag3-DnaJA1 co-chaperone complex may be regulated by this important post-translational modification. The data presented in this lecture should enhance your basic knowledge of the role of the SUMO-signaling pathway in both normal and diseased liver.

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