Growth-phase specific regulation of cviI/R based quorum sensing associated virulence factors in Chromobacterium violaceum by linalool, a monoterpenoid

• Published in: World journal of microbiology & biotechnology Vol. 38; no. 2; p. 23
• Main Authors: Kanekar, Saptami, Devasya, Rekha Punchappady
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2022; Springer Nature B.V
• Subjects: Acyclic Monoterpenes - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Applied Microbiology; Attenuation; Biochemistry; Biofilms - drug effects; Biomedical and Life Sciences; Biosensors; Biotechnology; Caenorhabditis elegans; Cell density; Cell lines; Chromobacterium - drug effects; Chromobacterium - genetics; Chromobacterium - growth & development; Chromobacterium - metabolism; Chromobacterium violaceum; Density; Environmental Engineering/Biotechnology; Gene expression; Gene Expression Regulation, Bacterial; Gene regulation; Genes; Gram-Negative Bacterial Infections - drug therapy; HEK293 Cells; Humans; In vivo methods and tests; Infections; Inhibitors; Life Sciences; Linalool; Lymphocytes; Lymphocytes T; Microbial Sensitivity Tests; Microbiology; Monoterpenes - pharmacology; Original Paper; Plant Extracts - pharmacology; Quorum sensing; Quorum Sensing - drug effects; Quorum Sensing - genetics; Survival; Synchronism; Synchronization; Violacein; Virulence; Virulence - drug effects; Virulence factors; Virulence Factors - genetics; Quorum sensing; In vivo infection; I/R regulation; Linalool; cviI/R regulation; C. violaceum
• ISSN: 0959-3993; 1573-0972
• DOI: 10.1007/s11274-021-03208-x

Quorum sensing (QS)-dependent gene regulation in bacteria performs a vital role in synchronization of cell-density-dependent functions. In Chromobacterium violaceum QS-dependent cvi I/R regulatory genes are activated during the mid- or late-exponential phase of growth. However, sufficient evidence is lacking on the role of QS inhibitors on gene regulation at different phases of growth. Hence, we report the role of linalool, a natural monoterpenoid on QS mediated gene regulation at different stages of growth in C. violaceum by performing biosensor, growth kinetic and gene expression studies. In vitro and in vivo studies were performed for establishing role of linalool in reducing the virulence and infection by using HEK-293 T cell lines and Caenorhabditis elegans models respectively. C. violaceum CV026 with C 6 -HSL was used as control. The results showed linalool to be a QS inhibitor with an estimated IC 50 of 63 µg/mL for violacein inhibition. At this concentration the cell density difference (delta OD 600 ) of 0.14 from the compound was observed indicating the quorum concentration. The expression of cvi I/R was initiated at mid-log phase (~ 18 h) and reached the maximum at 36 h in control whereas in treatment it remained significantly downregulated at all time points. The expression of violacein biosynthetic genes vio A, vio C, vio D and vio E was also downregulated by linalool. Infection studies with linalool showed higher survival rates in HEK-293T cell lines and C. elegans compared to the infection control. Taken together, this study proves linalool to be a QS inhibitor capable of attenuation of QS by controlling the cell density through cvi I/R downregulation at the early phase of growth and hence offering scope for its application for controlling infections.