Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections -- Bjarnsholt et al. 151 (12): 3873 -- Microbiology
Another reason as to why garlic seems to help so many with lyme/morgellons.
Several opportunistic pathogens are capable of organized expression of their arsenal of virulence factors in eukaryotic hosts. In order to do this, the bacteria have developed a chemically based, command language referred to as quorum sensing (QS) (Fuqua et al., 1994Down). QS enables bacteria to keep track of their numbers, and is considered to afford them a mechanism for minimizing host responses by delaying the production of virulence factors until sufficient bacteria have been amassed to overwhelm host defence mechanisms. Pseudomonas aeruginosa is a prevalent opportunistic human pathogen and one of the most common Gram-negative bacteria found in nosocomial and life-threatening infections of immuno-compromised patients (van Delden & Iglewski, 1998Down). Patients with cystic fibrosis (CF) are especially predisposed to infection with P. aeruginosa, and the bacterium is, despite intensive antibiotic therapy, responsible for high rates of morbidity and mortality (Lyczak et al., 2002Down; Koch & Høiby, 2000Down). Alternative strategies to conventional antibiotic treatments are therefore required. Our recently published tool for high-throughput screening, the QS inhibitor (QSI)-selector has allowed us to identify natural sources of potential, non-toxic QSI compounds (Rasmussen et al., 2005Down). The presence of such compounds in certain natural foods is interesting since it suggests that the diet may, to some extent, offer a natural prophylaxis against chronic P. aeruginosa infections. Garlic is renowned for its anti-fungal, anti-cancer and anti-microbial activities. The anti-microbial activities have been related to the presence of growth-inhibitory compounds, such as allicin and related derivatives (Ankri & Mirelman, 1999Down), and QS-blocking properties of garlic have been reported by us (Rasmussen et al., 2005Down, Persson et al., 2005Down).
We have previously demonstrated that a crude extract of garlic specifically inhibits QS-regulated gene expression in P. aeruginosa, as judged from DNA microarray-based transcriptomic analysis (Rasmussen et al., 2005Down). The expression of 167 genes, 92 of which were regulated by QS, was repressed by the extract (Rasmussen et al., 2005Down). The mechanism by which garlic compounds block QS is presently unknown. However, the effect is at a post-transcriptional level, since the amounts of mRNA of neither lasI, lasR, rhlI nor rhlR (the key components of the Las and Rhl QS communication systems in P. aeruginosa) were notably affected by the garlic treatment (Rasmussen et al. 2005Down; unpublished results). This suggests that the QSI molecules interact directly with the QS receptors by either a competitive or a non-competitive N-acylhomoserine lactone mechanism. The garlic extract used in this study contained very low amounts of toxic compounds (such as allicin) (Rasmussen et al., 2005Down). Treatment of in vitro biofilms with this extract was found to dramatically reduce the tolerance of the bacteria to the antibiotic tobramycin (Rasmussen et al., 2005Down). In addition, the extract was capable of attenuating bacterial virulence in a Caenorhabditis elegans nematode infection model (Rasmussen et al., 2005Down). We have previously demonstrated that the QS system is in fact a useful drug target, and delivered a proof of concept in which we demonstrated that the blockade of QS with the drug C-30 represents an effective approach for interfering with biofilm tolerance to antibiotic treatments and for attenuating the virulence of P. aeruginosa in a mouse infection model (Wu et al., 2004Down; Hentzer et al., 2003Down). Recently we have shown that the activation of polymorphonuclear leukocytes (PMNs) is blocked by P. aeruginosa QS signals in vitro (Bjarnsholt et al., 2005Down). In addition, QS mutants cause a faster activation of the host defence system in vivo (Bjarnsholt et al., 2005Down; Wu et al., 2001Down). These factors might account for the rapid clearing of bacteria deficient in QS (either by inactivating mutations or by treatment with QS-blocking drugs) as observed in mouse models of P. aeruginosa pulmonary infections (Wu et al., 2001Down, 2004; Hentzer et al., 2003Down; Bjarnsholt et al., 2005Down).
July 19th, 2009, 04:30 AM
Garlic is an effective quorem sensing inhibiter 
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