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.Many bacteria form organized communities of aggregated cells living in hydrated matrices of extracellular polymeric substances. These structures (termed "biofilms") are evolutionary adaptations by bacteria that enable them to survive in hostile environments and to colonize new ecological niches (7, 38). Bacteria living in biofilms have high resistance to antimicrobial agents, which constitutes a major health problem. Hence, investigation of the molecular mechanisms of biofilm formation and the effectiveness of new therapeutic agents in counteracting these mechanisms is becoming a productive line of research. Biofilms may develop with the participation of secreted molecules (termed "quorum-sensing signals") when a sufficiently high density of bacterial growth occurs at a certain location. In Gram-negative bacteria, acyl homoserine lactones (AHLs) have been identified as major quorum-sensing signals. The paraoxonases (PONs) constitute a group of lactonases ubiquitously expressed in human tissues. Recent evidence shows that they may play an important role in the fight against bacterial biofilm formation. In the present minireview, we summarize the current knowledge regarding PONs and their biological function while describing appropriate experiments to elucidate their possible role in antibacterial treatment. WHAT ARE THE PARAOXONASES?The PON enzyme family comprises 3 members, PON1, PON2, and PON3, the genes coding for which are located adjacent to each other on chromosome 7q21-22 (72, 81). In humans, PON1 and PON3 genes are mainly expressed in the liver and kidney and their protein products are found in the circulation bound to high-density lipoprotein (HDL) (45,55,58,79). Conversely, the PON2 gene is expressed a variety of tissues. Its protein product is an intracellular enzyme that is not, however, found in plasma (64). PON1 was first identified in 1953 by Aldridge, who, while examining the rates of hydrolysis of organophosphate insecticides in different tissues of rats and rabbits (5, 6), observed that rabbits exhibited a very high rate of paraoxon degradation in serum and that this compound was...

Strategies for Silencing Bacterial Communication

“…PONs exhibit lactonase activity and are capable of disrupting AHL-mediated QS systems of gram-negative bacteria (Camps et al 2011). Teiber et al reported that PONs, especially PON 2, efficiently degraded 3-oxo-C12-HSL, a key QS molecule produced by several bacterial species including P. aeruginosa, Burkholderia, Yersinia, Serratia and Aeromonas (Teiber et al 2008).…”

The Acyl-Homoserine Lactone Synthase YenI from Yersinia enterocolitica Modulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli O157:H7

“…Since AHLs are not naturally present in the RAJ, it is also possible that there are enzymes or factors expressed by the epithelial cells in the RAJ that can readily degrade AHLs. For example, a class of AHL-degrading enzymes found in mammals called paraoxonases (PONs) has been shown to degrade AHLs and inhibit the quorum-sensing regulation of bacteria (57). PON2 has the highest enzymatic capacity to degrade AHLs compared to other PONs (58,59).…”

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

“…Moreover, recent studies showed that PON2 expression is increased in cultured hematopoietic cells and mouse thymocytes after HIV-1 infection ( 16 ). The PON family also plays a role in innate immunity and can prevent bacterial infection ( 17 ).…”