Paraoxonases as potential antibiofilm agents: their relationship with quorum-sensing signals in Gram-negative bacteria

Abstract

The property of many bacteria to form biofilms constitutes a major health problem. Bacteria living in biofilms have a very high resistance to antibiotics. Biofilms may develop at a certain locations with the participation of secreted molecules, termed quorum-sensing signals, when a sufficient density of bacterial growth occurs. In Gram-negative bacteria, acyl homoserine lactones (AHL) have been identified as major quorum-sensing signals. The paraoxonases (PONs) constitute a family of enzymes comprising 3 members (PON1, PON2, and PON3) that have lactonase activity and are able to hydrolyze AHL. In this minireview, we summarize some existing basic knowledge on PON genetics, biochemistry, and function and describe recent research that reports evidence of the important roles that they may play in the organism's defense against biofilm formation. Finally, we propose some lines of future research that could be very productive.

FIG. 1.

Relationship between PON1 paraoxonase and arylesterase activities in different individuals. Plots of paraoxonase activity with 1 M NaCl versus arylesterase activity show three groups of individuals corresponding to the three paraoxonase phenotypes (AA, AB, and BB). (Reprinted from reference with permission of the publisher.)

FIG. 2.

Chemical structure of PON1. (a) View of the six-bladed β-propeller from above. The top of the propeller is, by convention, the face carrying the loops connecting the outer β-strand of each blade (strand D) with the inner strand of the next blade. The N and C termini and the two calcium atoms in the central tunnel of the propeller are shown. (b) A side view of the propeller with the three helices at the top (H1 to H3). (Reprinted from reference with permission of the publisher.)

FIG. 3.

(a) PON1 protein expression in mouse bronchiole epithelium. (b) PON1 protein expression in the mouse tongue. Bar, 100 μm. (c) PON1 gene expression in several tissues of the mouse. This enzyme is strongly expressed in the lung. BE, bronchiole epithelium; LP, lamina propria; SE, squamous epithelium; SM, skeletal muscle. The scale at the top of panel c represents arbitrary units. The arroheads indicate positive staining. (Adapted from references and with permission of the publishers.)