Ronen Hazan Lab
Antibiotics are perhaps the best medicine ever. They have saved the lives of millions and are one of the reasons for the vast increase in life expectancy during the past 100 years. Nevertheless, over the years of massive use of antibiotics it turned out that antibiotics have several negative aspects. First, they frequently fail to treat biofilms. Second, since they usually have wide range and nonspecific effects antibiotics harm also beneficial commensals bacteria belong to the microbiome. Last, in the past few years medicine begin to face emergence of multidrug resistant bacteria, mainly in hospitals. Consequently, there is an urgent need to enlarge our arsenal against pathogenic bacterial by developing novel, specific and less prone to promote resistance approaches that will be used in addition to antibiotics.
Our lab is interested in both basic science aspects and novel applicable approaches against pathogens including:
Members of the lab
1) Phage therapy. Phage therapy against bacteria preceded the findings of the first chemical antibiotics. Yet, phage therapy was abandoned mainly because of the limited ability, those days, to particularly identify and estimate the risk in phage harmful genes. Currently with the ease of high throughput sequencing and genome engineering, phage therapy is gaining new interest. In the lab we are working on developing phage therapy against selected pathogens.
2) Anti-infectives. In contrast to antibiotics, anti-infectives are designed to reduce virulence instead of killing bacteria. Thus, this therapeutic means are less prone to select for resistant mutants. Producing an anti-infective can be achieved by using bacterias’ own communication signals.
3) Light Therapy. Blue light therapy is used against cancer cells in combination with materials that are induced by the light to produce reactive oxygen species in order to kill the pathologic cells. Interestingly, as was previously found by our collaborator Dr. Osnat Feuerstein, numerous bacteria have such compounds intrinsically, which makes them naturally sensitive to blue light. In the lab we are studying cell-cell signals that affect bacterial sensitivity to blue light.
4) Environmental persisters. Persisters are subpopulation of any bacterial culture that confer phenotypically tolerance to antibiotics and are considered as one of the major threats in infectious disease medicine. We assume that this recognized phenomenon of antibiotics’ tolerance is only the tip of the iceberg of the persisting mechanism used by the bacteria to survive in stress conditions. To test this idea we choose to study the persistence ability of anaerobic bacteria under oxygen. A major part of both commensal and pathogenic bacteria are anaerobes. Moreover, it is known that although these bacteria are frequently exposed to oxygen they may survive. We hypothesized that one of their survival mechanisms is by entering a persistence/dormant stage. In the lab we test this hypothesis and its implications on antibiotic tolerance.
5) Nanoparticles – One of the foremost challenges of current medical microbiology is to combat bacterial biofilms. Our collaborators, Dr. Beyth and Prof. Weiss have developed surface integrated antibacterial nanoparticles that attract bacteria and kill them. Interestingly, killing is being observed also in biofilm layers that are not in direct contact with the nanoparticles, indicating a possible existence of bacterial programed cell death within the biofilm. This signals might be used in inducing bacterial programmed cell death.
Blue light therapy. Cells of Pseudomonas aeruginosa were grown in biofilm. Cells were exposed to blue light for 3 minutes (right panel) and stained with live/dead stain where red denotes dead cells. About 70% of were killed by the light treatment
Ronen Hazan (Ph.D) – PI
Leron Khalifa (PhD student) – Phage Therapy and killing by nanoparticles
Daniel Gelman (Medicine Student) – Phage therapy
Yair Brosh (Dental Medicine student) – Ex – vivo root canal models for phage therapy against E. faecalis.
Fatma Ab (MA student) – Oxygen persisters and oxygen therapy.
Chaya Shuman – (Hadassah and Haradic Colleges) – Light therapy.
Dana Kesler Shvero (PhD and DMD student) – Mechanisms of bacterial killing by nanoparticles.
Call for students
Our lab is seeking for students in all levels for basic science projects in microbiology and bioinformatics and applicable projects involved in development of new anti-infectious tools.
Nurit Beyth (DMD, PhD) from the Dental faculty of the Hebrew University – Phage therapy and nanoparticles.
Osnat Feuerstein (DMD, PhD), dental faculty of the Hebrew University – Light therapy.
Yok Ai Que (MD, PhD) from University of Lausanne and leader of the Phagoburn project (http://www.phagoburn.eu/), Switzerland – Phage therapy
Ronit Cohen Poradosu (MD) from Sourasky Medical Center (Ichilov Hospital).
Prof. Ervin Weiss (MD, PhD), Head of the department of prosthodontics of the Hebrew University, Hadassah.
Some of the technologies we use are:
Comprehensive anaerobic system that allows the study of anaerobic oral, gut and other related bacteria.
High throughput sequencing of 16S, RNAseq and genomics.
Static and dynamic biofilms.
Kinetic analysis of bacterial growth.
Molecular biology of phages and relatively less investigated species of bacteria.
And, of course, all the classical methods in microbiology and molecular biology
EFDG1 phage. Our first E. faecalis phage was isolated from sewage samples. It eradicates both logarithmic, stationary and biofilm cells.
TEM photo of the bacteriophage EFDG1