Designed potent multivalent chemoattractants for Escherichia coli.
Bacterial chemotactic responses are initiated when certain small molecules (i.e., carbohydrates, amino acids) interact with bacterial chemoreceptors. Although bacterial chemotaxis has been the subject of intense investigations, few have explored the influence of attractant structure on signal generation and chemotaxis. Previously, we found that polymers bearing multiple copies of galactose interact with the chemoreceptor Trg via the periplasmic binding protein glucose/galactose binding protein (GGBP). These synthetic multivalent ligands were potent agonists of Escherichia coli chemotaxis. Here, we report on the development of a second generation of multivalent attractants that possess increased chemotactic activities. Strikingly, the new ligands can alter bacterial behavior at concentrations 10-fold lower than those required with the original displays; thus, they are some of the most potent synthetic chemoattractants known. The potency depends on the number of galactose moieties attached to the oligomer backbone and the length of the linker tethering these carbohydrates. Our investigations reveal the plasticity of GGBP; it can bind and mediate responses to several carbohydrates and carbohydrate derivatives. These attributes of GGBP may underlie the ability of bacteria to sense a variety of ligands with relatively few receptors. Our results provide insight into the design and development of compounds that can modulate bacterial chemotaxis and pathogenicity.
Gestwicki
J E
JE
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Strong
L E
LE
Borchardt
S L
SL
Cairo
C W
CW
Schnoes
A M
AM
Kiessling
L L
LL
D002135:Calcium-Binding Proteins; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D005690:Galactose / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018715:Microscopy, Video; D008958:Models, Molecular; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D033902:Periplasmic Binding Proteins; D013329:Structure-Activity Relationship
D002135:Calcium-Binding Proteins; D002630:Chemotactic Factors; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; C023550:galactose-binding protein; D005690:Galactose