Diallyl disulfide from garlic oil inhibits Pseudomonas aeruginosa virulence factors by inactivating key quorum sensing genes

Abstract

Garlic oil can disrupt the quorum sensing (QS) pathways of the opportunistic pathogen Pseudomonas aeruginosa; however, the underlying mechanisms for this effect are unclear. Diallyl disulfide (DADS) is one of the most abundant sulfur-containing compounds in garlic oil. This study investigated the effects of DADS on the growth, virulence factor production (elastase, pyocyanin, biofilm, and swarming motility), and essential gene expression of P. aeruginosa PAO1, particularly as they apply to QS and virulence. DADS at 1.28 mg/mL did not affect P. aeruginosa PAO1 growth, although it decreased elastase and pyocyanin production, biofilm formation, and swarming motility. Each of these phenomena is regulated by the three QS systems of P. aeruginosa PAO1 (las, rhl, and pqs). Real-time q-PCR revealed that DADS down-regulated the transcription levels of several important QS genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR) in the three systems. Furthermore, the transcription levels of QS-regulated virulence genes were also down-regulated. The lasB gene, encoding LasB elastase, is co-regulated by the las, rhl, and pqs systems, and thus the down-regulation of genes across the three systems further down-regulated lasB. Additionally, phzM (encoding pyocyanin), pslB (responsible for the production of a biofilm matrix polysaccharide), and chiC (encoding chitinase) were positively activated by LasR, and a decrease in lasR transcription further down-regulated the transcription of phzM, pslB, and chiC. Hence, DADS inhibits P. aeruginosa PAO1 virulence factors by inactivating the transcription of key genes across three different QS systems.

Antimicrobial properties of hydrophobic compounds in garlic: Allicin, vinyldithiin, ajoene and diallyl polysulfides (Review)

“…Bacteria have a barrier system, biofilm formation, which inhibits the entry of disinfectants, antibiotics and host immune molecules into the bacterial cells and is a major cause of the drug-resistance of bacteria (44). In addition, QS molecules, such as AHL regulate biofilm formation, intercellular communication, bacterial population and other processes (3,4,11,46). The inhibition of biofilm formation and QS has been studied in various scientific and technological fields.…”

“…Therefore, it is difficult for allicin to reach the infected sites of the body as an intact form. Recent studies have demonstrated that sulfur-containing compounds derived from garlic, such as diallyl disulfide (DAS 2 ) and ajoene, inhibit biofilm formation and the QS of bacteria, even though the antimicrobial activities of these compounds are lower than those in medical antibiotics used in clinical settings (11)(12)(13)(14)(15)(16). Furthermore, Slachmuylders et al and others have demonstrated that some natural products, which exert an inhibitory effect on biofilm formation, have antibiotic-potentiating activity (17)(18)(19)(20).…”

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

“…Moreover, DADS down-regulated several important genes ( lasI , lasR , rhlI , rhlR , pqsA , and pqsR ) of the las , rhl , and pqs QS systems. Therefore, we concluded that DADS inhibits P. aeruginosa PAO1 pathogenic factors by inactivating the key genes of las , rhl , and pqs QS systems (Li et al, 2018).…”

“…Pseudomonas aeruginosa is a ubiquitous, clinically significant, Gram-negative bacillus and an opportunistic human pathogen (Stover et al, 2000; Lee et al, 2018). P. aeruginosa infections are particularly difficult to eradicate because this pathogen is prone to acquire resistance to multiple antibiotics and it prefers to form antibiotic-resistant biofilms (Galloway et al, 2012; He et al, 2018; Li et al, 2018). In recent years, a number of studies have reported that garlic extract contains P. aeruginosa QS inhibitors, including ajoene, a sulfur compound from garlic (Rasmussen et al, 2005; Bodini et al, 2009; Harjai et al, 2010; Jakobsen et al, 2012).…”

“…In addition, garlic extract has been demonstrated to increase the fragility of P. aeruginosa biofilms and inhibit their formation (Bjarnsholt et al, 2005). Previously, we found that diallyl disulfide (DADS), an ingredient from garlic oil (Li et al, 2014), could decrease elastase and pyocyanin production, biofilm formation, and swarming motility in P. aeruginosa PAO1, but did not affect bacterial growth (Li et al, 2018). Real time q-PCR revealed that the related virulence genes were down-regulated by DADS.…”