CANCELLED:  The seminar by Petra A. Levin, Professor, Department of Biology, and Program Director, Plant and Microbial Biosciences, Washington University in St. Louis, has been cancelled.

ABSTRACT

Title:  "pH Mediates Cell Envelope Protein Activity and Antibiotic Sensitivity in Bacteria"

Anyone who has ever measured protein activity in vitro knows that pH is a critical parameter.  At the same time, we know little about the effect of environmental pH on the activity of cell surface proteins. Over the course of its lifetime, the human commensal Escherichia coli can experience pH values ranging from 4 to 8 as it makes its way through the gut, into the environment, and back again. To illuminate the impact of environmental pH on activity of E. coli cell surface proteins, we analyzed the growth and morphology of wild type and mutant bacteria across arrange of pH values. We were particularly interested in the enzymes required for synthesizing the bacterial cell wall. Largely exposed to the environment on the outside the cytoplasmic membrane, these enzymes are extraordinarily redundant at neutral pH, with an ~4 to 1 ratio of enzymes to reactions.   

Our data suggest that a subset of these so-called “redundant” enzymes are required for maximal fitness across pH environments. Among these pH specialists are the class A penicillin binding proteins PBP1 a and PBP1 b; defects in these enzymes attenuate growth and impair cell wall integrity in alkaline and acidic conditions, respectively. Genetic, biochemical, and cytological studies demonstrate that differential activity across pH environments significantly alters cell morphology, via changes in activity of the division machinery, and enhances intrinsic resistance to cell wall active antibiotics up to an order of magnitude. Together, our findings reveal previously thought to be redundant enzymes are instead specialized for distinct environmental niches, thereby ensuring robust growth and cell wall integrity in a wide range of conditions.