Diallyl Disulfide From Garlic Oil Inhibits Pseudomonas aeruginosa Quorum Sensing Systems and Corresponding Virulence Factors

Abstract

Previously, we determined that diallyl disulfide (DADS) from garlic oil can inhibit Pseudomonas aeruginosa PAO1 pathogenic factors by inactivating the transcription of key genes from three quorum sensing (QS) systems (las, rhl, and pqs) based on the effects of DADS on growth, virulence factor production (elastase, pyocyanin, biofilm, and swarming motility), and RNA transcription (real-time q-PCR). To further investigate the mechanisms underlying the inhibition of the three P. aeruginosa QS systems by DADS, high-throughput RNA and proteome sequencing techniques were used to study differences in the transcriptional and proteome expression of P. aeruginosa PAO1 following treatment with DADS. The RNA-seq and proteomic data are available via NCBI Gene Expression Omnibus database with accession number GSE118801 and ProteomeXchange with identifier PXD011144, respectively. The experimental results indicated that all key genes of the three QS systems (las, rhl, and pqs) of P. aeruginosa PAO1 as well as the virulence factors (including exoprotease LasA, elastase LasB, lectin LecA and LecB, pyocyanin biosynthesis, and biofilm formation) regulated by these three QS systems were inhibited. This is consistent with our previous studies on the physiology, biochemistry, and RNA expression of P. aeruginosa treated with DADS. Additionally, our results also indicated that bacterial motility, chemotaxis, and two-component systems were inhibited by DADS treatment. All these changes abolish the sensitivity of P. aeruginosa PAO1 to environmental stimuli and cause the cells to be in a state of passivation. Further research is needed to determine how QS systems regulate these functions. Our findings could potentially contribute to the treatment and control of P. aeruginosa infection, virulence, and pathogenicity.

Antimicrobial Effect and the Mechanism of Diallyl Trisulfide against Campylobacter jejuni

“…The antimicrobial effects of DATS or other diallyl sulfide derivatives have not been studied in C. jejuni before. On the other hand, several studies have been conducted on investigating the antimicrobial effect of DAS, DADS, DAT, DATS on P. aeruginosa ; DATS showed an equal antimicrobial effect to the multidrug-resistant P. aeruginosa as the garlic essential oil, and both were stronger compared to DAS, DADS and DAT according to the MIC results [ 19 , 21 ]. A previous study treated P. aeruginosa by 2.84 mg/L for 120 h and observed a 50% decrease of cell density by the hemocytometer counting method, while the inhibition efficiency was increased with the increasing of treatment dose [ 22 ].…”

“…A previous study showed that the sulfides from virulence genes could regulate the quorum sensing (QS) signal molecules and extracellular virulence factors of Pseudomonas aeruginosa both in vivo and in vitro [ 18 ]. Further studies also proved that DADS could inhibit the expression of las , rhl and pqs for QS autoinducer synthesis [ 19 ]. In addition, diallyl sulfide derivatives from garlic also proved to inhibit the QS transcriptional regulators LuxR and LasR [ 20 , 21 ].…”

Diallyl sulfide from garlic suppresses quorum‐sensing systems of Pseudomonas aeruginosa and enhances biosynthesis of three B vitamins through its thioether group

“…A previous study reported that four diallyl sulfides (DAS, DADS, DATS, and DATTS) in garlic can inhibit LuxR QS monitoring system (Persson et al ., 2005). In our previous study, we found that DADS from garlic inhibited the gene expression of the QS systems and related virulence genes of the PAO1 strain (Li et al ., 2019). The difference between DADS and DAS is that DADS inhibited the transcription of all the key genes in the three QS systems, while DAS did not inhibit lasI and pqsH .…”

“…Similar to DAS, DADS inhibited key genes in the three QS systems of the PAO1 strain (Li et al ., 2018, 2019). One difference between DAS and DADS is that DADS inhibits the transcriptions of all key genes in the three QS systems of the PAO1 strain, including lasI and pqsH , whereas DAS does not.…”

“…Some other ingredients from garlic were also preliminarily detected to have QS inhibitory activity on luxI / luxR , including DAS, DADS, DATS, DATTS, 2‐vinyl‐4H‐1,3‐dithiine and 3‐vinyl‐3,4‐dihydro‐1,2‐dithiine (Persson et al ., 2005; Cady et al ., 2012). In our previous study, we verified that DADS in garlic can inhibit QS of P. aeruginosa ; DADS inhibits the production of virulence factors in P. aeruginosa by inhibiting the expression of the key genes in the three QS systems, namely las , rhl and pqs (Li et al ., 2018, 2019). At the same time, we also detected that DAS from garlic inhibit QS of P. aeruginosa .…”