Making the Bacteria Eat Its Nemesis

The synthesis and delivery of antibacterial agents has been a growing field of research owing to increasing bacterial resistance to known agents and, hence, a constant need to develop more efficacious ones. But taking a step back and exploring nature for a solution, one comes across some essential oils. Essential oils are called thus since they carry the distinctive scent or essence of the plant. Some of these naturally occurring oils—especially thymol, cinnamaldehyde, carvacrol and allyl isocyanate (AITC)—have been shown to possess antibacterial properties. They cause inactivation of the proton motive force, interfere with salt concentrations and other viral elements and metabolites from within the cells, ultimately leading to cell death.[1] Many studies indicate that the antimicrobial effect of essential oil constituents depend on their hydrophobicity and, consequently, on their partition in the cytoplasmic membrane.[1] The relationship between the strength of the antimicrobial and its chemical structure is important for a better interpretation of the effectiveness of the antimicrobial compounds. The potential antimicrobial activity of cinnamaldehyde is attributed to the functional aldehydic group, which facilitates the interaction with molecules such as proteins and nucleic acids.[2] AITC has an amphiphilic structure and exerts its antimicrobial activity by acting on the cell membrane.[3] Moreover, it could alter the protein structure by reacting with free amino groups and disulphide bonds of proteins.

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However, these essential oils are hydrophobic and volatile in nature; this limits their miscibility, efficiency, and availability to bacterial cells for in vitro studies. Hence, these have to be administered via a system that can increase delivery in aqueous solutions without loss due to volatility. Mesoporous silica nanoparticles (MSNs) present a very powerful means of delivering molecules which have inherently low aqueous solubility.[4][5] MSNs are monodisperse and colloidally stable silica particles which have uniform pore size, comprised of a honeycomb-like porous structure with ‘empty’ channels which can encapsulate or adsorb materials. Their particle size, shape and porosity can be controlled during the synthetic procedure, which can be suitably applied in different systems. The chemical and thermal stability of silica, along with its biocompatibility, makes it an ideal platform for theranostics. The surface chemistry can be tuned by reacting with different functionalities that provide scope for controlled and targeted delivery of an encapsulated substance. They are potential carriers for both hydrophobic and hydrophilic molecules with differing shapes and functionalities, due to the ability to tune the porosity.[6][7][8]. In order to achieve selective delivery with particles which are otherwise unvectored, the concept of specific pore capping is particularly useful.[9]

The delivery of these essential oils involved MSNs being functionalized with lactose on their surface to facilitate the targeting of E.coli bacterial cells. E.coli bacterial cells produce the enzyme beta-galactosidase intracellularly that ferments lactose. Lactose, being a disaccharide, is large enough to cap the openings on MSNs by intermolecular hydrogen bondings, thereby retaining the oils within the pores. Its subsequent enzymatic degradation to release the antibacterial oil intracellularly would enhance its efficiency further. Thus, the development of the MSNs, the efficient loading of the oils inside them, and their capping with lactose generates an antibacterial delivery system that entices the bacteria to consume its own antibacterial agent.

References

  1. S. Burt, Essential oils: their antibacterial properties and potential applications in foods - a review, Int. J. Food Microbiol. 94, pp. 223–253, 2004.
  2. H. J. D. Dorman and S. G. Deans, Antimicrobial agents from plants: antibacterial activity of plant volatile oils, J. of Appl. Microbiol. 88, pp. 308–316, 2000.
  3. S. Tunc, E. Chollet, P. Chalier, L. Preziosi-Belloy, and N. Gontard,, Combined effect of volatile antimicrobial agents on the growth of Penicillium notatum, Int. J. Food Microbiol. 113, pp. 263–270, 2007.
  4. K. Moller, J. Kobler, and T. Bein, Colloidal suspensions of nanometer-sized mesoporous silica, Adv. Funct. Mat. 17, pp. 605–612, 2007.
  5. J. Kobler, K. Moller, and T. Bein, Colloidal suspensions of functionalized mesoporous silica nanoparticles, ACS Nano 2, pp. 791–799, 2008.
  6. C. Y. Lai, B. G. Trewyn, D. M. Jeftinija, K. Jeftinija, S. Xu, S. Jeftinija, and V. S. Y. Lin, A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules, J. Am. Chem. Soc. 125, pp. 4451–4459, 2003.
  7. M. J. K. Thomas, I. Slipper, A. Walunj, A. Jain, M. E. Favretto, P. Kallinteri, and D. Douroumis, Inclusion of poorly soluble drugs in highly ordered mesoporous silica nanoparticles, Int. J. Pharm. 387, pp. 272–277, 2010.
  8. Y. Z. Zhang, Z. Z. Zhi, T. Y. Jiang, J. H. Zhang, Z. Y. Wang, and S. L. Wang, Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan, J. Control. Release 145, pp. 257–263, 2010.
  9. H. A. Meng, M. Xue, T. A. Xia, Y. L. Zhao, F. Tamanoi, J. F. Stoddart, J. I. Zink, and A. E. Nel, Autonomous in vitro anticancer drug release from mesoporous silica nanoparticles by pH-sensitive nanovalves, J. Am. Chem. Soc. 132, pp. 12690–12697, 2010.

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