Prof. Nitzan's Lab
Advanced Studies on Photoinactivation of Bacteria
Prof. Yeshayahu Nitzan is an Associate Professor in the Mina and Everard Goodman Faculty of Life Sciences. Nitzan and his group study the photoinactivation of Gram-positive and Gram-negative bacteria by using photosensitizer–antibiotic conjugates and liposome-encapsulated water-soluble photosensitizers. In another approach to inactivation of bacteria, conducted in collaboration with Dr. R. Cahan and Dr. M. Nisnevitch from the Ariel University Center, the group uses intracellular antimicrobial photodynamic therapy and light-activated antibacterial surfaces.
Antimicrobial Activity of Organotellurium Compounds
In collaboration with Prof. Benjamin Sredni, Nitzan and his group study the bactericidal activity of organotellurium compounds on the gram-negative bacteria of the familyEnterobacteriaceae. This work represents a new approach to using an immunomodulating drug as an antimicrobial and antifungal drug. The group is currently testing a new organotellurium drug against a variety of bacteria and yeast.
Nitzan, along with Dr. Rachel Lubart and her team have shown that visible light at high intensities can kill bacteria in infected wounds. The sensitivity of bacteria to broadband visible light enhanced wound healing, resulting in faster healing of the infected wounds.
Nanoparticles and Their Use as Bacteriocides
In collaboration with Prof. (Emeritus) Aharon Gedanken’s team, Nitzan and his group have demonstated that nanoparticles can kill pathogenic bacteria on direct contact or when they are bound to surfaces. They have shown antimicrobial activity of metalloxide nanoparticles and the enhanced effect of photosensitization on the bactericidic activity of these nanoparticles.
Ecological and Environmental Aspects of Microbes
In collaboration with Dr. Cahan and Dr. Nisnevitch, Nitzan and his students are characterizing toluene-degrading bacterial species and preparing bioelectrical cells that degrade toluene by the special bacteria and produce electric current. They also immobilize formaldehyde-metabolizing enzymes from bacteria for removal of formaldehyde.
Past Research Subjects in Medical Microbiology and Infectious Diseases
Photodynamic Therapy by Exogenic and Endogenic Porphyrins
Nitzan and his group exposed bacteria to light in the presence of a photosensitizer. This “photokilling:” process, which employs a class of light-sensitive compounds called porphyrins, may be used for treating infected burns and skin wounds. Photoactivated porphyrins display a potent cytotoxic activity against a variety of gram-positive bacteria.
Upon illumination of membrane-bound porphyrin, molecules generate singlet oxygen and hydroxyl free radicals, which sensitize biomolecules that lead to bacterial cell death. For gram-negative bacteria, photosensitization is possible only with a positively charged porphyrin. Photoinactivation is not dependent on the antibiotic resistance of the bacteria nor is it dependent on its resistance to radiation. Thus the photodynamic capabilities of metal-free porphyrins effectively act as photosensitizers for bacteria and yeasts.
Nitzan and his group, in collaboration with Prof. Zvi Malik, investigated the mechanisms of photoinactivation and target sites of photodynamic action in the bacterial cell. The group used electron microscopy to examine the damage in intracellular structures as well as the changes in the elemental content of the bacterial cells. In addition, they investigated the synergistic action of different antibiotics that enable better penetration of the porphyrins into yeast cells.
Nitzan and his group also studied photodynamic therapy by endogenic porphyrins, a method of photoinactivation based on the ability of delta-amino levulinic acid (ALA) to act as an inducer of endogenic synthesis of porphyrins. This induction process increases the number of light-sensitive porphyrins generated inside bacterial cells, a process that renders these bacteria susceptible to photodynamic therapy and has been successfully used for treating acne. A significant photokilling effect can be seen by illuminating the ALA induced cultures as well as intracellular damages and changes in the elemental content.
Porins: Structure and Function
Nitzan and his group have isolated pore-forming proteins from the outer membrane of various gram negative bacteria in a variety of growth conditions. They investigated the penetration ability of sugars, amino acids and antibiotics through these porins. They purified the pore forming proteins, sequenced them and isolated the analogous genes.
In addition, they worked on predicting the secondary structure and finding the sequence of the loop areas located at the external side of the bacteria. These external “loops” of the pore-forming proteins have been studied with the aim of characterizing how these loops contribute to the adhesion of the pathogenic bacteria to mammalian cells and how they are responsible for the pathogenic behavior of the microorganism by induction of cytokins in infected patients.
Together with collaborators from the “Asaff Harofe” Medical Center the group examined adherence mechanisms of bacteria (especially Staphylococci) to bones. They searched forstrategies to block the adhesion of bacteria to fractured bones and suggested prevention of the adherence by using exogenous photosensitizers.