Mohammad Shavez Khan

Inhibition of quorum sensing regulated bacterial functions by plant essential oils with special reference to clove oil

Aims:  To evaluate quorum sensing (QS) inhibitory activity of plant essential oils using strains of Chromobacterium violaceum (CV12472 and CVO26) and Pseudomonas aeruginosa (PAO1).

Broad-spectrum inhibition of AHL-regulated virulence factors and biofilms by sub-inhibitory concentrations of ceftazidime

Quorum sensing (QS) in bacteria is a density dependent communication system that regulates the expression of genes, including production of virulence factors in many pathogens. The emergence of antibiotic resistance among pathogenic bacteria represents a major threat in both hospitals as well as environmental settings. Interference of quorum sensing (QS)-regulated virulence factors and biofilms is a recognized anti-pathogenic therapy. Safe, stable and effective anti-QS agents are needed to combat diseases caused by multidrug-resistant bacteria. The present study was performed to assess the inhibitory effect of third generation antibiotic ceftazidime against Gram-negative bacterial pathogens. Sub-MICs of ceftazidime demonstrated dose dependent inhibition of QS regulated virulence traits and biofilm formation in various strains of Chromobacterium violaceum (CV12472 and CVO26), Pseudomonas aeruginosa (PAO1 and PAF79) and Aeromonas hydrophila (WAF38). β-galactosidase assay revealed ceftazidime inhibited the las and pqs QS systems in P. aeruginosa. Alongside, in vivo studies demonstrated enhanced survival of Caenorhabditis elegans after the treatment with the drug. Molecular docking analysis showed the high binding affinity of ceftazidime which represents its QS inhibitory activity. By highlighting the broad spectrum anti-quorum sensing and biofilm inhibiting activities against 3 different bacterial pathogens, ceftazidime seems a more potent candidate in counteracting the infections caused by drug resistant bacteria.

New tailored substituted benzothiazole Schiff base Cu(II)/Zn(II) antitumor drug entities: effect of substituents on DNA binding profile, antimicrobial and cytotoxic activity

New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o‒vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, 1H & 13C NMR, ESI−MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C30H22CuN5O7S2], [C30H20Cl2CuN5O7S2], [C30H20CuF2N5O7S2], [C30H22N4O4S2Zn], [C30H20Cl2N4O4S2Zn], and [C30H20F2N5O7S2Zn], with CT‒DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by K b and K sv values which gave higher binding propensity for chloro-substituted Cu(II) [C30H20Cl2CuN5O7S2] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski’s rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens viz., E. coli, S. aureus, P. aeruginosa, B. subtilis, and C. albicans. The cytotoxicity of the complexes [C30H20Cl2CuN5O7S2], [C30H20CuF2N5O7S2], [C30H20Cl2N4O4S2Zn], and [C30H20F2N5O7S2Zn] were evaluated against five human cancer cell lines viz., MCF‒7 (breast), MIA‒PA‒CA‒2 (pancreatic), HeLa (cervix) and Hep‒G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C30H20Cl2CuN5O7S2] complex, exhibited pronounced specific cytotoxicity with GI50 value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix.

Horizontal Gene Transfer in Soil and the Rhizosphere: Impact on Ecological Fitness of Bacteria

The ecological fitness of soil- and root-associated bacterial communities is a key element for soil fertility and plant health as well as plant stress tolerance. Genetic variability in bacterial populations is maintained through mutation and gene acquisition. Horizontal gene transfer (HGT) is accomplished by conjugation, transformation, and transduction both in vitro and under natural conditions. Mobile genetic elements (MGEs) play a significant role in gene dissemination in bacterial communities and increase their adaptability, survival, and ability to colonize different environmental niches. In this context, bacterial conjugative plasmids encoding resistance genes, degradative genes, and tolerance to stress conditions are of much significance. The biofilm mode of bacterial growth further enhances gene exchange and increase the fitness and competitiveness of bacteria. Microcosm studies reveal a number of factors influencing the HGT process in soil. Considering the importance of HGT, a better understanding of genetic processes in the rhizosphere will further help in effective exploitation of naturally engineered bacteria for sustainable agriculture.

Interference of phosphane copper (I) complexes of β-carboline with quorum sensing regulated virulence functions and biofilm in foodborne pathogenic bacteria: A first report

Foodborne pathogens are one of the major cause of food-related diseases and food poisoning. Bacterial biofilms and quorum sensing (QS) mechanism of cell–cell communication have also been found to be associated with several outbreaks of foodborne diseases and are great threat to food safety. Therefore, In the present study, we investigated the activity of three tetrahedrally coordinated copper(I) complexes against quorum sensing and biofilms of foodborne bacteria. All the three complexes demonstrated similar antimicrobial properties against the selected pathogens. Concentration below the MIC i.e. at sub-MICs all the three complexes interfered significantly with the quorum sensing regulated functions in C. violaceum (violacein), P. aeruginosa (elastase, pyocyanin and alginate production) and S. marcescens (prodigiosin). The complexes demonstrated potent broad-spectrum biofilm inhibition in Pseudomonas aeruginosa, E. coli, Chromobacterium violaceum, Serratia marcescens, Klebsiella pneumoniae and Listeria monocytogenes. Biofilm inhibition was visualized using SEM and CLSM images. Action of the copper(I) complexes on two key QS regulated functions contributing to biofilm formation i.e. EPS production and swarming motility was also studied and statistically significant reduction was recorded. These results could form the basis for development of safe anti-QS and anti-biofilm agents that can be utilized in the food industry as well as healthcare sector to prevent food-associated diseases.

Nanoparticles as Quorum Sensing Inhibitor: Prospects and Limitations

The emergence and worldwide spread of multi-drug resistant bacterial pathogens and slow pace of drug discovery with novel mode of action has necessitated search for alternative or new strategies to combat bacterial infection. Targeting virulence and pathogenicity of pathogens controlled by quorum sensing (QS) is considered as a promising anti-infective drug target. Several molecules both natural and synthetic were reported to interfere quorum sensing and are potential candidates for anti-infective drugs. The inhibition of QS might successfully attenuate and eradicate the microbial pathogens in combination with host immune system. It is expected that QS inhibition will exert less selection pressure for development of resistance among pathogenic bacteria. The recent progress in nanobiotechnology have given a greater hope for the development of novel anti-QS agents/formulations with improved therapeutic potential, enhanced targeted delivery with lesser toxicity to host system. The improved action of nano-formulations is a fascinating ability compared to their bulk. Recently, nanoparticles such as metal nanoparticles are reported to exhibit promising anti-QS activity both in vitro and in vivo. Nanomaterials are also been tested as vehicle for targeted delivery of conventionally used antimicrobial agents. There is greater scope of manipulation in nano-based formulations according to desired needs making such therapeutic strategies more efficient. Of note, the risks associated with the application of nanoparticles in drug delivery, diagnostics, production of improved biocompatible material or preventing biofilm formation on medical devices, etc. are needed to be scrutinized. In this article, we have made an attempt to review the recent advancements in nanoparticle as anti-QS agents and progress made on nano-based formulations with promising prospects and limitations.

Quorum Sensing Interference by Natural Products from Medicinal Plants: Significance in Combating Bacterial Infection

Plant derived natural products and phytocompounds are known for their broad spectrum biological activities and are of great therapeutic value in traditional system of medicine. The role of medicinal plants and phytocompounds in the treatment of various diseases including bacterial infection are widely documented. Anti-infective compounds from medicinal plants may provide new drug leads. Bacterial cell to cell communication has been become attractive target for the development of novel anti-infective measures that do not rely on the use of antibiotics. Targeting Quorum sensing has been emerge as promising strategy to combat bacterial infections as it is unlikely to develop multidrug resistance pathogens since it does not impose any selection pressure. In this review, we have surveyed the recent literature available on plant extracts, essential oils and phytocompounds exhibiting anti-quorum sensing properties. Further, significance of phytocompounds to combat bacterial infections caused by MDR bacteria has been discussed.

Antioxidant properties and anti-mutagenic potential of Piper Cubeba fruit extract and molecular docking of certain bioactive compounds

Abstract Spices and herbs are recognized as sources of natural antioxidants and thus play an important role in the chemoprevention of diseases and aging. Piper cubeba is one among them and known for its medicinal properties for decades. Various biological activities are associated with its extract and phytocompounds. However, the anti-mutagenic activity of antioxidant rich extract is less explored. In this study, we performed the fraction-based antioxidant activity of P. cubeba using four different assays and evaluated the anti-mutagenic activity of most potent antioxidant fraction using Salmonella typhimurium tester strains against four mutagens (methyl methanesulfonate [MMS], sodium azide [SA], benzo(a)pyrene, and 2-aminoflourene) respectively. Among all tested fractions at 25–200 µg/ml, ethanolic extract revealed highest antioxidant activity and significant anti-mutagenicity against both direct and indirect acting mutagens at least one tester strain. Phytochemical analysis by gas chromatography–mass spectrometry (GC/MS) revealed the presence of various phytocompounds including copaene, isocaryophyllene, α-cubebene, etc. Molecular docking studies on DNA binding interactions of GC/MS detected phytocompounds highlight the possible mode of binding. In summary, these in vitro studies have provided the scientific basis for validation of using this plant in the traditional system of medicine and highlighted the need for exploring the role of various compounds for therapeutic efficacy. On the other hand, synergistic interaction among phytocompounds is to be explored to optimize or standardize the extracts for the exploitation in modern phytomedicine.