Guava Leaf Extract Inhibits Quorum-Sensing and Chromobacterium violaceum Induced Lysis of Human Hepatoma Cells: Whole Transcriptome Analysis Reveals Differential Gene Expression

Abstract

Quorum sensing (QS) is a process mediated via small molecules termed autoinducers (AI) that allow bacteria to respond and adjust according to the cell population density by altering the expression of multitudinous genes. Since QS governs numerous bioprocesses in bacteria, including virulence, its inhibition promises to be an ideal target for the development of novel therapeutics. We found that the aqueous leaf extract of Psidium guajava (GLE) exhibited anti-QS properties as evidenced by inhibition of violacein production in Chromobacterium violaceum and swarming motility of Pseudomonas aeruginosa. The gram-negative bacterium, C. violaceum is a rare pathogen with high mortality rate. In this study, perhaps for the first time, we identified the target genes of GLE in C. violaceum MTCC 2656 by whole transcriptome analysis on Ion Torrent. Our data revealed that GLE significantly down-regulated 816 genes at least three fold, with p value≤0.01, which comprises 19% of the C. violaceum MTCC 2656 genome. These genes were distributed throughout the genome and were associated with virulence, motility and other cellular processes, many of which have been described as quorum regulated in C. violaceum and other gram negative bacteria. Interestingly, GLE did not affect the growth of the bacteria. However, consistent with the gene expression pattern, GLE treated C. violaceum cells were restrained from causing lysis of human hepatoma cell line, HepG2, indicating a positive relationship between the QS-regulated genes and pathogenicity. Overall, our study proposes GLE as a QS inhibitor (QSI) with the ability to attenuate virulence without affecting growth. To the best of our knowledge, this is the first report which provides with a plausible set of candidate genes regulated by the QS system in the neglected pathogen C. violaceum.

Radical Scavenging Activities of Lagerstroemia speciosa (L.) Pers. Petal Extracts and its hepato-protection in CCl4-intoxicated mice

“…There may be some more phytochemicals (remained in the GCMS data beyond the known ones) in LFE which are yet to be identified as hepatoprotective agents. In one of our previous reports, it was shown that multiple constituents of a PPE may act synergistically or additively to affect the biological system [57]. There are also other reports on using combination of compounds to gain higher therapeutic effectiveness over singly administered compound(s) [58].…”

Prospective bacterial quorum sensing inhibitors from Indian medicinal plant extracts

“…In an earlier study, guava leaf extract was demonstrated to have similar dose‐dependent inhibition of violacein production without affecting the growth of C. violaceum (Ghosh et al . ). Moreover, genome‐wide transcriptome analyses of C. violaceum cells grown in the presence and absence of guava leaf extract have revealed a panel of QS‐controlled genes, including the virulence factors (Ghosh et al .…”

Genesis of Personalized Medicine: Relevance of Ayurveda in the Present Millennium

“…Applying simple biotechnological approaches in combination to Ayurveda, we have been able to decipher mechanisms of action of plant drugs in single form [24][25][26][27] or poly herbal fermented preparation, which not only became able to inhibit biofilm formation of Pseudomonas aeruginosa, or restrict quorum sensing of Chomobacterium violaceum, but also significantly inhibited several natural isolates found to possess resistance towards different classes of conventional antibiotic drugs. Attempts have been made to check the activity of this Ayurveda based drug against various kinds of enteropathogenic metallo beta lactamase producing organisms, and to identify probable mechanisms of action(s) with the help of standard scientific methodology currently adapted in pharmaceutical industry and laboratories across the globe.…”