Sara Selgrade

Joined Program: 2002
Previous Degree: B.A. Molecular Biology & Biochemistry, Middlebury College
Miller Lab
selgrade (at) u.washington.edu

Research:
Pseudomonas aeruginosa is a ubiquitous bacterium found in soil and water that can cause opportunistic lung infections in cystic fibrosis patients. This project focuses on the use of antimicrobial peptides (AMPs) to treat chronic P. aeruginosa infections. AMPs are cationic and bind to negatively charged bacterial membranes in order to lyse cells. In response, bacteria including P. aeruginosa can alter their cell surfaces so as to reduce AMP binding. The addition of amino sugar molecules blocks the negative phosphate groups on the bacterial outer membrane. This surface change renders P. aeruginosa more resistant to AMPs. The genes responsible for the biosynthesis of the amino sugar, PA3552-3559, as well as the two-component regulatory system, pmrAB, thought to control the biosynthesis operon were previously identified.

We have found that pre-exposure to low concentrations of AMPs induces resistance to subsequent challenge with AMPs in P. aeruginosa. Mutation of the two-component sensor PmrB renders the bacteria more sensitive to AMPs, but appears to affect induced resistance only minorly. In addition, low level pre-treatment with AMPs induces the quorum sensing gene pqsB, a physiological change that does not depend upon the PmrAB regulatory system, but rather mimics a membrane stress response. These results indicate that induced resistance to AMPs in P. aeruginosa may involve not only surface modifications but also a more general stress response that may tie into membrane stability and quorum sensing. Future work on this project will include investigations of the role of pqsB in induced resistance to AMPs and further investigation of the regulation of the aminoarabinose biosynthetic pathway.