Virulence attenuation of pathogenic bacteria without the application of antibiotics is a strategy that reduces the threat of infection while limiting the evolution of multidrug resistant strains. Some bacterial pathogenic behavior is regulated by population density dependent gene expression, known as quorum sensing (QS), which relies on the synthesis, transmission, and perception of small signal molecules called autoinducers. While at least seven types of QS are known and distinguishable by the molecular form of autoinducer employed, Gram-negative bacteria, such as Pseudomonas aeruginosa, predominantly “communicate” population density using N-acyl-L-homoserine lactones (AHLs). One consideration that is crucial to developing Gram-negative QS modulating strategies, as well as modeling QS under ‘real-world’ conditions, is the ability to distinguish between the ring-closed (bioactive) and ring-open (bio-inactive) forms. While some AHLs have been studied under different conditions for their hydrolysis (ring-opening) rates, no quantitative and comprehensive model for this degradation exists. Here, we employ 1H-NMR to monitor the hydrolysis of various AHLs under standard laboratory conditions at fixed acidities to develop such a model. This preliminary model provides valuable insight into the availability of bioactive AHLs at biologically and chemically relevant pH conditions and is a valuable tool in the development of QS-control strategies and evaluation of AHL-centric chemical assays and studies.

Quantitative determination of abiotic AHL hydrolysis by 1H NMR

2019 Spring National Meeting

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