Jeyachandran Akshay

Bio: Jeyachandran Akshay is an academic researcher from Central University of Tamil Nadu. The author has contributed to research in topics: Chromobacterium violaceum & Ethyl acetate. The author has an hindex of 1, co-authored 1 publications receiving 5 citations.

Inhibition of Quorum Sensing and Biofilm Formation in Chromobacterium violaceum by Fruit Extracts of Passiflora edulis.

Abstract: Chromobacterium violaceum (C. violaceum) is a Gram-negative, rod-shaped facultatively anaerobic bacterium implicated with recalcitrant human infections. Here, we evaluated the anti-QS and antibiofilm activities of ethyl acetate extracts of Passiflora edulis (P. edulis) on the likely inactivation of acyl-homoserine lactone (AHL)-regulated molecules in C. violaceum both by in vitro and in silico analyses. Our investigations showed that the sub-MIC levels were 2, 1, and 0.5 mg/mL, and the concentrations showed a marked reduction in violacein pigment production by 75.8, 64.6, and 35.2%. AHL quantification showed 72.5, 52.2, and 35.9% inhibitions, inhibitions of EPS production (72.8, 36.5, and 25.9%), and reductions in biofilm formation (90.7, 69.4, and 51.8%) as compared to a control. Light microscopy and CLSM analysis revealed dramatic reduction in the treated biofilm group as compared to the control. GC-MS analysis showed 20 major peaks whose chemical structures were docked as the CviR ligand. The highest docking score was observed for hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester bonds in the active site of CviR with a binding energy of -8.825 kcal/mol. Together, we found that hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester remarkably interacted with CviR to inhibit the QS system. Hence, we concluded that hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester of P. edulis could likely be evaluated for treating C. violaceum infections.

Computational and Biological Evaluation of β-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents

Abstract: Bacterial resistance to antibiotics is an increasing public health threat as it has the potential to affect people at any stage of life, as well as veterinary. Various approaches have been proposed to counteract the bacterial resistance development. Tackling bacterial virulence is one of the most promising approaches that confer several merits. The bacterial virulence is mainly regulated by a communication system known as quorum sensing (QS) system. Meanwhile, bacteria can sense the adrenergic hormones and eavesdrops on the host cells to establish their infection, adrenergic hormones were shown to enhance the bacterial virulence. In this study, β-adrenoreceptor blockers were proposed not only to stop bacterial espionage on our cells but also as inhibitors to the bacterial QS systems. In this context, a detailed in silico study has been conducted to evaluate the affinities of twenty-two β-blockers to compete on different structural QS receptors. Among the best docked and thermodynamically stable β-blockers; atenolol, esmolol, and metoprolol were subjected to further in vitro and in vivo investigation to evaluate their anti-QS activities against Chromobacterium violaceum, Pseudomonas aeruginosa and Salmonella typhimurium. The three tested β-blockers decreased the production of QS-controlled C. violaceum, and the formation of biofilm by P. aeruginosa and S. typhimurium. Additionally, the tested β-blockers down-regulated the P. aeruginosa QS-encoding genes and S. typhimurium sensor kinase encoding genes. Furthermore, metoprolol protected mice against P. aeruginosa and S. typhimurium. Conclusively, these investigated β-blockers are promising anti-virulence agents antagonizing adrenergic hormones induced virulence, preventing bacterial espionage, and blocking bacterial QS systems.

Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria

Abstract: Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on the cells of the host by sensing adrenergic hormones and other neurotransmitters, and in turn, these neurotransmitters can induce bacterial pathogenesis. In this direction, α-adrenergic blockers were proposed as an anti-virulence agents through inhibiting the bacterial espionage. The current study aimed to explore the α-blockers’ anti-QS activities. Within comprehensive in silico investigation, the binding affinities of seven α-adrenoreceptor blockers were evaluated towards structurally different QS receptors. From the best docked α-blockers into QS receptors, terazosin was nominated to be subjected for further in vivo and in vitro anti-QS and anti-virulence activities against Chromobacterium violaceum and Pseudomonas aeruginosa. Terazosin showed a significant ability to diminish the QS-controlled pigment production in C. violaceum. Moreover, Terazosin decreased the P. aeruginosa biofilm formation and down-regulated its QS-encoding genes. Terazosin protected mice from the P. aeruginosa pathogenesis. In conclusion, α-adrenergic blockers are proposed as promising anti-virulence agents as they hinder QS receptors and inhibit bacterial espionage.

Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease.

Abstract: Periodontal disease is primarily associated with bacterial infection such as dental plaque. Dental plaque, an oral biofilm harboring a complex microbial community, can cause various inflammatory reactions in periodontal tissue. In many cases, the local bacterial invasion and host-mediated immune responses lead to severe alveolar bone destruction. To date, plaque control, non-surgical, and surgical interventions have been the conventional periodontal treatment modalities. Although adjuvant therapies including antibiotics or supplements have accompanied these procedures, their usage has been limited by antibiotic resistance, as well as their partial effectiveness. Therefore, new strategies are needed to control local inflammation in the periodontium and host immune responses. In recent years, target molecules that modulate microbial signaling mechanisms, host inflammatory substances, and bone immune responses have received considerable attention by researchers. In this review, we introduce three approaches that suggest a way forward for the development of new treatments for periodontal disease; (1) quorum quenching using quorum sensing inhibitors, (2) inflammasome targeting, and (3) use of FDA-approved anabolic agents, including Teriparatide and sclerostin antibody.

Synthesis of gallotannin capped iron oxide nanoparticles and their broad spectrum biological applications

Abstract: Green synthesized nanoparticles (NPs) have attracted enormous attention for their clinical and non-clinical applications. A natural polyphenol, gallo-tannin (GT) was used to reduce and cap the Fe2O3-NPs. GT-Fe2O3-NPs were synthesized following co-precipitation of FeCl3 and FeSO4·7H2O with GT. Fe2O3-NPs absorbed light at 380 nm. Physicochemically, Fe2O3-NPs were spherical with slight aggregation and average diameter of 12.85 nm. X-ray diffraction confirmed crystallinity and EDX revealed the elemental percentage of iron and oxygen as 21.7% and 42.11%, respectively. FT-IR data confirmed the adsorption of gallo-tannin functional groups. Multiple drug-resistant (MDR) Escherichia coli (ESβL), Pseudomonas aeruginosa (ESβL), and Staphylococcus aureus were found susceptible to 500–1000 μg GT-Fe2O3-NPs per ml. In synergy, Fe2O3-NPs enhanced the efficiency of some antibiotics. GT-Fe2O3 NPs showed significant (P ≤ 0.05) inhibition of growth and biofilm against MDR E. coli, P. aeruginosa, and S. aureus causing morphological and biofilm destruction. Violacein production (quorum sensing mediated) by C. violaceum was inhibited by GT-Fe2O3-NPs in a concentration-dependent manner with a maximum decrease of 3.1-fold. A decrease of 11-fold and 2.32-fold in fungal mycelial growth and human breast cancer (MCF-7) cell viability, respectively was evident. This study suggests a plausible role of gallo-tannin capped Fe2O3-NPs as an alternative antibacterial, antiquorum sensing, antibiofilm, antifungal, and anti-proliferative agent.

Biofilm-Associated Agr and Sar Quorum Sensing Systems of Staphylococcus aureus Are Inhibited by 3-Hydroxybenzoic Acid Derived from Illicium verum

Abstract: Biofilm-producing Staphylococcus aureus (S. aureus) is less sensitive to conventional antibiotics than free-living planktonic cells. Here, we evaluated the antibiofilm activity of Illicium verum (I. verum) and one of its constituent compounds 3-hydroxybenzoic acid (3-HBA) against multi-drug-resistant S. aureus. We performed gas chromatography–mass spectroscopy (GC-MS) to identify the major constituents in the methanolic extract of I. verum. Ligand–receptor interactions were studied by molecular docking, and in vitro investigations were performed using crystal violet assay, spreading assay, hemolysis, proteolytic activity, and growth curve analysis. The methanolic extract of I. verum inhibited S. aureus at 4.8 mg/mL, and GC-MS analysis revealed anethole, m-methoxybenzaldehyde, and 3-HBA as the major constituents. Molecular docking attributed the antibiofilm activity to an active ligand present in 3-HBA, which strongly interacted with the active site residues of AgrA and SarA of S. aureus. At a subinhibitory concentration of 2.4 mg/mL, the extract showed biofilm inhibition. Similarly, 3-HBA inhibited biofilm activity at 25 μg/mL (90.34%), 12.5 μg/mL (77.21%), and 6.25 μg/mL (62.69%) concentrations. Marked attrition in bacterial spreading was observed at 2.4 mg/mL (crude extract) and 25 μg/mL (3-HBA) concentrations. The methanol extract of I. verum and 3-HBA markedly inhibited β-hemolytic and proteolytic activities of S. aureus. At the lowest concentration, the I. verum extract (2.4 mg/mL) and 3-HBA (25 μg/mL) did not inhibit bacterial growth. Optical microscopy and SEM analysis confirmed that I. verum and 3-HBA significantly reduced biofilm dispersion without disturbing bacterial growth. Together, we found that the antibiofilm activity of I. verum and 3-HBA strongly targeted the Agr and Sar systems of S. aureus.