Roles of Pseudomonas aeruginosa Autoinducers and their Degradation Products, Tetramic acids, in Bacterial Survival and Behavior in Ecological Niches

Abstract

Pseudomonas aeruginosa, an opportunistic pathogen, is known to mainly use N-acylhomoserine lactones (AHLs) as autoinducers. Recent progress in this field demonstrated that not only AHLs, but also their degradation products, tetramic acids, may have some biological activities. The present study examined the roles of Pseudomonas autoinducers and tetramic acids in bacterial survival and behavior in ecological niches. P. aeruginosa autoinducers and the tetramic acid derivatives were chemically synthesized, and the structure-activity correlation was investigated. Some tetramic acids derived from AHLs caused a significant reduction in the viability of P. aeruginosa in a concentration dependent manner (30-300 μM). The smaller the inoculum of bacteria, the stronger the bactericidal activity that was observed. The data from tetramic acid derivatives indicated the keto-enol structure of tetramic acid to be critical for the antibacterial activity. Exogenous tetramic acid did not induce significant changes in the formation of biofilm or production of exoproducts such as pyocyanin and elastase. Tetramic acid and disinfectants acted synergistically to kill P. aeruginosa. These results suggest the AHL-degradation product tetramic acid to be useful for bacterial control.

Targeting Staphylococcus aureus Quorum Sensing with Nonpeptidic Small Molecule Inhibitors

“…These data are broadly in agreement with the staphylococcal MICs for 5 and 7 reported by Lowery et al 14 Interestingly, the shorter chain compound 5-HE-C4-TMA 3 , which we found was not active against S. aureus , has been reported to kill P. aeruginosa (15) but not C. difficile . 13 TMAs with 3-acyl chains of 10–14 carbons inhibited growth and agr with differences between the MIC and IC 50 values ranging from little different (e.g., 5-HE-C14-TMA 8 ) to 5-fold (e.g., 5-HE-C11-TMA 6 ).…”

“…23 Since iron has been reported to abolish the antibacterial activity of 5 toward C. difficile and P. aeruginosa , 13,15 we synthesized TOA (Table 3, 14 – 18 ; Table S2, S17 – S24 ) variants of the TMAs in which the ring nitrogen is replaced with oxygen. We predicted that the tetronic acid structure would not chelate iron, as it largely exists as a 4-enolic tautomer 24 as opposed to the TMA structure where the 3-exoenolic tautomer in ( Z )-configuration predominates.…”

“…14 The physiological function of 5 in P. aeruginosa is not known, but it is capable of weakly inhibiting the LasR/3-oxo-C 12 -HSL-dependent activation of the elastase ( lasB ) gene 6 and reducing P. aeruginosa viability. 15 In contrast to 3-oxo-C 12 -HSL, 5 is also a ferric ion chelator. 8 However, while it does not function as a siderophore for P. aeruginosa , 16 iron was reported to abolish the antibacterial activity of 5 toward P. aeruginosa (15) and Clostridium difficile .…”

“…15 In contrast to 3-oxo-C 12 -HSL, 5 is also a ferric ion chelator. 8 However, while it does not function as a siderophore for P. aeruginosa , 16 iron was reported to abolish the antibacterial activity of 5 toward P. aeruginosa (15) and Clostridium difficile . 13 In common with 3-oxo-C 12 -HSL, 5 also exhibits immune suppressive activity in a murine peripheral blood lymphocyte proliferation assay and is cytotoxic toward Jurkat 6 but not bone-marrow-derived macrophage cells.…”

Rediscovery of the Microbial World in Microbial Ecology

“…Examination of dormant microbes is required for comprehensive understanding of microbial communities, because dormant microbes provide clues to the hidden function of microbial community and they may contribute to stability of microbial ecosystems. Recently, physiological states in response to environmental stress have been well-studied in microbial ecology (16, 22, 67, 69). …”