Dr. Zvi Hayouka

Novel antimicrobial agents for food applications

Food-borne and other infectious enteric diseases are significant sources of morbidity and mortality worldwide. The high demand for minimally processed, easily prepared and ready-to-eat ‘fresh’ food products poses a major challenge for food safety and quality.

Recent outbreaks of food-borne microbial pathogens have driven the search for innovative ways to inhibit microbial growth in foods while maintaining quality, freshness and safety.

In my lab we will develop chemical tools to inhibit microbial or fungal growth in food.

The interdisciplinary research program will combine food science, peptide chemistry, biochemistry and microbiology toward the design of novel antimicrobial agents for applications in food science.

In the media:

יוצאים מהקופסה: כנס ראשון בארץ לאריזות חכמות, יוזמה של ד״ צבי חיוקה

כתבה של רויטרס שהתפרסמה בסופש האחרון על המעבדה ועל הפפטידים האנטימיקרוביאלים שלנו

Reuters: Aug 17, 2017 - New peptide could help fight drug-resistant 'superbugs'. Israeli scientists develop a peptide that could be used in antimicrobial medicines that could hold the key to treating infections in a post-antibiotic era. Amy Pollock reports.

Fighting Back Against Antibiotic Resistant Superbugs

A unique antibiotic that can kill bacteria that are resistant to conventional antibacterials without damaging the cells that store them has been developed by scientists at the Hebrew University of Jerusalem. The pioneering study was carried out by Dr. Zvi Hayouka and colleagues.

חוקרים ישראלים פיתח אנטיביוטיקה לחיידקים עמידים

על פי הפרסום, ד"ר חיוקה ועמיתיו במכון לביוכימיה בפקולטה לחקלאות באוניברסיטה העברית מצאו חומר טבעי שמחסל חיידקים שנמצאו כעמידים בפני אנטיביוטיקה

חוקרים פיתחו אנטיביוטיקה נגד חיידקים העמידים לאנטיביוטיקה

באנטיביוטיקות תעשה לך מלחמה: חוקרים באוניברסיטה העברית פיתחו אנטיביוטיקה נגד חיידקים העמידים לאנטיביוטיקה

Israeli Discovery May Help Ward Off Famine

Researchers are seeking regulatory approval for a peptide that can kill bacteria – whether throughout a hospital or inside a milk carton.

הצפרדע שתציל את העולם מרעב

אריזת פלא שמונעת מהמזון להתקלקל, כפתורי מעלית ומעקות של מדרגות שדוחים חיידקים, ותוצרת חקלאית שלא מרקיבה, הם רק שלושה מהיישומים האפשריים של מחקר חדש פורץ דרך, שסינתז חומרים היודעים להשמיד חיידקים

 

See also: Zvi_Hayouka

List of Publications

Peer-Reviewed Publications

2019

  • Amso Z, Hayouka Z. Antimicrobial random peptide cocktails: a new approach to fight pathogenic bacteria. Chem Commun (Camb). 2019; 55, 2007-2014. (Invited Review- Featured article).
  • Yehuda A, Slamti L, Malach E, Lereclus D and Hayouka Z. Elucidating the Hot Spot Residues of Quorum Sensing Peptidic Autoinducer PapR by Multiple Amino Acids Replacements, Frontiers Microbiology, 2019; 10, 1246.
  • Tal Stern Bauer, Barak Menagen, David Avnir and Zvi Hayouka. Random peptide mixtures entrapped within a copper-cuprite matrix: new antimicrobial agent against methicillin-resistant Staphylococcus aureus. Scientific reports. 9(1):11215
  • Vinayak Ghate⁠a⁠, Einat Zelinger⁠, Hagit Shoyhet⁠, Zvi Hayouka. Inactivation of Listeria monocytogenes on paperboard, a food packaging material, using 410nm light emitting diodes. Food control, 2019, 96, 281-290.

2018

  • Carla Vilela, Mia Kurek, Zvi Hayouka, Bettina Rocker, Selçuk Yildirim, Maria Dulce Antunes, Julie Nilsen-Nygaard, Marit Pettersen, Carmen Freire. A concise guide to active agents for active food packaging. Trends in Food Science & Technology, 2018, 80, 212-222 (Review).
  • Yehuda A, Slamti L, Bochnik-Tamir R, Malach E, Lereclus D and Hayouka Z. Turning off Bacillus cereus quorum sensing system with peptidic analogs. Chemical Communication, 2018, 54, 9777-9780.
  • Ocłoń E, Solomon G, Hayouka Z, Gertler A. Preparation of biologically active monomeric recombinant zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) recombinant growth hormones. Fish Physiology and Biochemistry, 2018, 44, 1215-1222.
  • Stern T and Hayouka Z. Identification and eradication of pasteurized bovine milk associated bacteria using random antimicrobial peptide mixtures. Journal of Peptide Science, 2018, e3088 .
  • Topman S, Bochnick Tamir H, Burdman S and Hayouka Z. Random peptide mixture as crop protection agents. Microbial biotechnology, 2018. ‏
  • Hu S, Zhao Y, Hayouka Z, Wang D, Jiao S. Inactivation kinetics for Salmonella typhimurium in red pepper powders treated by radio frequency heating (2018). Food controlIn press.
  • Oclon, E, Solomon G, Hayouka Z, Salame T, Goffin V, Gertler A. Novel reagents for human prolactin research: large-scale preparation and characterization of prolactin receptor extracellular domain, non-pegylated and pegylated prolactin and prolactin receptor antagonist. Protein Engineering, Design, and Selection. In press.

2017

  • Hayouka Z*, Bella A, Stern T, Ray S, Jiang H, Grovenor CRM, Ryadnov MG. Binary Encoding of Random Peptide Sequences for Selective and Differential Antimicrobial Mechanisms. Angew Chem Int Ed Engl. 2017 . doi:10.1002/anie.201702313
    * corresponding author

2016:

  • Stern T, Zelinger E, Hayouka Z. Random peptide mixtures inhibit and eradicate methicillin-resistant Staphylococcus aureus biofilms.Chem Commun (Camb). 2016 Jun 4;52(44):7102-5.

2015:

  • Hayouka Z, Thomas NC, Mortenson DE, Satyshur KA, Weisblum B, Forest KT, Gellman SH. Quasiracemate Crystal Structures of Magainin 2 Derivatives Support the Functional Significance of the Phenylalanine Zipper Motif. J Am Chem Soc. 2015 Sep 23;137(37):11884-7.

2014:

  • Ilona Patursky-Polischuk, Judith Kasir, Rachel Miloslavski, Hayouka Z, Mirit Hausner-Hanochi, Miri Stolovich-Rain, Pinchas Tsukerman, Moshe Biton, Rajini Mudhasani, Stephen N. Jones and Oded Meyuhas. PLOS ONE 2014. Oct 22;9(10)
  • Chakraborty, Saswata; Liu, Runhui; Hayouka, Z; Chen, Xinyu; Ehrhardt, Jeffrey; Lu, Qin; Burke, Eileen; Yang, Yiqing; Weisblum, Bernard; Wong, Gerard; Masters, Kristyn; Gellman, Samuel. Ternary Nylon-3 Copolymers as Host-Defense Peptide Mimics:  Beyond Hydrophobic and Cationic Subunits. J. Am. Chem. Soc. 2014 Oct 15;136(41)
  • Liu R, Chen X, Chakraborty S, Lemke JJ, Hayouka Z, Chow C, Welch RA, Weisblum B, Masters KS, Gellman SH. Tuning the biological activity profile of antibacterial polymers via subunit substitution pattern. J. Am. Chem. Soc. 2014  Mar 19;136(11):4410-8
  • Miloslavski R, Cohen E, Avraham A, Iluz Y, Hayouka Z, Kasir J, Mudhasani R, Jones SN, Cybulski N, Rüegg MA, Larsson O, Gandin V, Rajakumar A, Topisirovic I, Meyuhas O. Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner. J Mol Cell Biol. 2014. Jun;6(3):255-66.

2013:

  • Hayouka Z, David E. Mortenson, Dale F. Kreitler, Bernard Weisblumb, Katrina T. Forestc, Samuel H. Gellmana. Evidence for Phenylalanine Zipper-Mediated Dimerization in the X-Ray Crystal Structure of a Magainin 2 Derivative. J. Am. Chem. Soc. 2013. Oct 23;135(42):15738-41
  • Hayouka Z, Chakraborty S, Liu R, Samuel H. Gellman. Interplay Among Subunit Identity, Composition, Chain Length and Stereochemistry in the Activity Profile of Sequence-Random Oligomer Mixtures. J. Am. Chem. Soc. 2013 Aug 14;135(32):11748-51
  • Chakraborty S, Liu R, Hayouka Z, Samuel H. Gellman. Studying the effect of cyclic versus acyclic nylon-3 polymers. ACS macro letter, 2013
  • Liu R, Chen X, Hayouka Z, Chakraborty S, Falk SP, Weisblum B, Masters KS, Gellman SH. Nylon-3 polymers with selective antifungal activity.J Am Chem Soc. 2013 Apr 10;135(14):5270-3
  • Liu R, Chakraborty S, Hayouka Z, Samuel H. Gellman. Nylon-3 polymer as antifungal agent.  J. Am. Chem. Soc. 2013, 135, 5270-3.

Older publications:

  • Hayouka Zvi, A. Levin, M. Hurevich, D. E. Shalev, A. Loyter, C. Gilon, A. Friedler. Backbone versus side chain to side chain cyclization of LEDGF 361-370 as an anti HIV-1 lead compound. Bioorg Med Chem. 2012, 20, 3317-22.
  • Helman A, Cinnamon E, Mezuman S, Hayouka Zvi, Von Ohlen T, Orian A, Jiménez G, Paroush Z. Phosphorylation of Groucho Mediates RTK Feedback Inhibition and Prolonged Pathway Target Gene Expression. Current Biology. 2011, 21, 1102-1110.
  • Levin, H. Benyamini,  HayoukaZvi, A. Friedler, A. Loyter. Peptides that bind the HIV-1 integrase and modulate its enzymatic activity: Kinetic studies and mode of action. FEBS,2011 Jan;278(2):316-30.
  • Levin A, Hayouka Zvi, Friedler A, Loyter A. Transportin 3 and importin α are required for effective nuclear import of HIV-1 integrase in virus-infected cells. Nucleus.1(5) :422-431, 2010.
  • Levin A, Hayouka Zvi, Friedler A, Loyter A. Nucleocytoplasmic shuttling of HIV-1 integrase is controlled by the viral Rev protein. Nucleus. 1(2):190-201, 2010.
  • Hayouka Zvi., Levin, A., Loyter, A., and Friedler, A. Peptide inhibitors of the HIV-1 integrase protein. Bulletin of the Israel Chemical Society 25, 20-28, 2010.
  • Hayouka Zvi, M. Hurevich, A. Levin, M. Maes, D. E. Shalev, A. Loyter, C. Gilon, A. Friedler. Conformational cyclic peptide libraries: mimicking the bioactive conformation of LEDGF/p75 and inhibiting HIV-1 integrase. Bioorganic and Medicinal Chemistry.  18(23):8388-95 (2010).
  • Levin A, Hayouka Zvi, Helfer M, Brack-Werner R, Friedler A, Loyter A. Stimulation of the HIV-1 integrase enzymatic activity and cDNA integration by a peptide derived from the integrase protein. Biopolymers, 93(8): 740-51, 2010.  
  • Garty S, Kimelman-Bleich N, Hayouka Zvi, Cohn D, Friedler A, Pelled G, Gazit D. Peptide-modified "smart" hydrogels and genetically engineered stem cells for skeletal tissue engineering. Biomacromolecules. 11(6):1516-26, 2010.
  • Levin A, Hayouka Zvi, Friedler A, Loyter A Specific eradication of HIV-1 from infected cultured cells. AIDS Res Ther. (7):31, 2010.
  • Levin A, Hayouka Zvi, Friedler A, Loyter A. Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells. J. Virol. (7) :177, 2010.
  • Levin A, Hayouka Zvi, Friedler A, Loyter A. Over-expression of the HIV-1 Rev promotes death of nondividing eukaryotic cells. Virus Genes. 2010 Jun;40(3):341-6. .
  • Hayouka Zvi, Aviad Levin, Michal Maes, Eran Hadas, Deborah E. Shalev, David J. Volsky, Abraham Loyter and Assaf Friedler. Mechanism of action of the HIV-1 Integrase Inhibitory Peptide LEDGF 361-370. Biochem Biophys Res Commun. 394(2): 260-5, 2010.
  • Levin A, Rosenbluh J, Zvi Hayouka, Friedler A, Loyter A. Integration of HIV-1 DNA is regulated by interplay between viral Rev and cellular LEDGF/p75 proteins. Mol Med. 2010 Jan-Feb;16(1-2):34-44
  •  Levin A, Hayouka Zvi, Brack-Werner R, Volsky DJ, Friedler A, Loyter A. Novel regulation of HIV-1 replication and pathogenicity: Rev inhibition of integration. Protein Eng Des Sel.  (12):753-63, 2009.
  •  Aviad Levin, Zvi Hayouka, Ruth Brack-Werner, David J. Volsky, Assaf Friedler and Abraham Loyter. A novel function of HIV-1 Rev limits integration and extends cells survival. Protein Eng Des Sel. 22(12):753-63, 2009.
  • Michal Maes, Aviad Levin, Zvi Hayouka, Abraham Loyter, Assaf Friedler. Peptide inhibitors of HIV-1 integrase: from mechanistic studies to development of improved leads. Bioorg Med Chem. 17(22): 7635-42, 2009.
  • Aviad Levin, Zvi Hayouka, Markus Helfer, Ruth Brack-Werner, Assaf Friedler and Abraham Loyter.  Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration. PLoS ONE, 4(1): e4155, 2009.
  • Ronen Gabizon, Michal Mor, Masha M. Rosenberg, Lena Britan, Zvi Hayouka, Moshe Kotler, Deborah E. Shalev and Assaf Friedler. Using Peptides to Study the Interaction between the p53 Tetramerization Domain and HIV-1 Tat. Biopolymers: Peptide science, 90(2): 105-116, 2007.
  • Hayouka Zvi, Joseph Rosenbluh, Aviad Levin, Abraham Loyter & Assaf Friedler. Peptides derived from HIV-1 Rev inhibit HIV-1 Integrase in a shiftide mechanism. Biopolymers: Peptide science, 90(4):481-7, 2008. 
  • Ayelet Armon-Omer, Aviad Levin, Hayouka Zvi, Karin Butz, Felix Hoppe-Seyler, Shoshana Loya, Amnon Hizi, Assaf Friedler and Abraham Loyter. Correlation between shiftide activity and HIV-1 integrase inhibition by a peptide selected from a combinatorial library. Journal of Molecular Biology, 376:  971-982, 2007.
  • Coster G, Hayouka Zvi, Argaman L, Friedler A, Brandeis M and Goldberg M. Linking the DNA damage response and cell cycle regulation: MDC1 directly interacts with the APC/C;  J. Biol. Chem., 288: 32053-64, 2007.
  • Kirshenboim N, Hayouka Zvi, Friedler A, Hizi A. Expression and characterization of a novel reverse transcriptase from the LTR retrotransposon Tf1; Virology, 366(2): 263-276,  2007.
  • Rosenbluh J, Hayouka Zvi, Loya S, Levin A, Armon-Omer A, Britan L, Hizi A, Kotler M, Friedler A and Loyter A. An interaction between the HIV-1 Rev and IN proteins: a base for the development of anti-HIV peptides, J Biol Chem; 282(21):15743-53, 2007.
  • Hayouka Zvi, Rosenbluh J, Levin A, Loya S, Lebendiker M, Veprintsev DB, Kotler M, Hizi A, Loyter A and  Friedler A. Inhibiting HIV-1 Integrase by Shifting its Oligomerization Equilibrium; Proc Natl Acad Sci U S A. 104(20): 8316-21, 2007. 

 

See also: Zvi_Hayouka

Research Interests

Novel antimicrobial agents for food applications

Food-borne and other infectious enteric diseases are significant sources of morbidity and mortality worldwide. The high demand for minimally processed, easily prepared and ready-to-eat ‘fresh’ food products poses a major challenge for food safety and quality.

Recent outbreaks of food-borne microbial pathogens have driven the search for innovative ways to inhibit microbial growth in foods while maintaining quality, freshness and safety.

In my lab we will develop chemical tools to inhibit microbial or fungal growth in food.

The interdisciplinary research program will combine food science, peptide chemistry, biochemistry and microbiology toward the design of novel antimicrobial agents for applications in food science.

 

Main research goals:

1. Development of antimicrobial packaging and food preservatives

We have recently designed random peptide mixture materials that display broad antimicrobial activities.1 These peptide mixtures are random in terms of sequence but highly controlled in terms of chain length, composition and stereochemistry (Figure 1). We will explore and expand the use of random peptide mixtures as components of new antimicrobial food packaging and as preservatives to prevent contamination and increase the shelf life of food.

 

fig1zvi
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Figure 1: Standard Fmoc-based solid-phase synthesis methods were used, but a mixture of protected amino acids rather than a single protected amino acid was added for each coupling step. The results of three coupling steps are illustrated. In this process, each bead of the solid support bears many growing chains with many different sequences.

 

2. Designing of novel antibiotic compounds to target food poisoning bacteria

Our research will involve development of new approaches for the design and synthesis of chemical entities that are targeted toward unexplored bacterial biological interactions. We will study the toxin-antitoxin (TA) system in bacteria.

These systems are present in many bacterial species, including major human pathogens. Each TA system comprises an antitoxin protein that binds to and inactivates its corresponding toxin protein. Upon degradation of the antitoxin in response to external stress, the toxin is released to induce bacterial death.

Inhibition of TA interactions offers an opportunity for the development of selective antibacterial compounds because no mammalian homologs of TA pairs are known.

fig2zvi
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Figure 2: Toxin (T, blue) antitoxin (A, gray) interaction and inhibition. (Upper panel) When toxin binds the antitoxin, its toxic activity is inhibited so the bacteria will grow. (Lower panel) Upon addition of our designed inhibitors (IN, red) TA interaction is inhibited and the toxin is free to induce bacterial death.

Open positions are available for highly motivated MSc, PhD and Post doctoral students.

More details are available here or please contact Zvika Hayouka 
Email: zvi.hayouka@mail.huji.ac.il

1. Hayouka Z, Chakraborty S, Liu R, Samuel H. Gellman. Interplay Among Subunit Identity, Composition, Chain Length and Stereochemistry in the Activity Profile of Sequence-Random Oligomer Mixtures. J. Am. Chem. Soc. 2013, 135, 11748−11751.

 

 

See also: Zvi_Hayouka

Lab Members

Dr. Einav Malach – Lab Technician

Dr. Irena Peri – Lab advisor

Heli Bochnik-Tamir - PhD Candidate Exploring Toxin anti-toxin system in bacteria at the molecular level.

Tal Stern - PhD candidate, Studying Food borne pathogens and developing chemical tools to tackle them.

Avishag Yehuda - MSc candidate, exploring the quorum sensing sysem of food borne pathogen Bacillus cereus.

Shiri Topman - MSc candidate, studying plant pathogen bacterial diseases and developing chemical tools to eradicate these disease.

Hadar Cheriker - Amirim Student, Exploring non thermal pasteurization processes.

Hagar Setty - Amirim Student, Studying toxin anti-toxin system in bacteria

Dana Shwartz - Undergraduate student

Karin Feldman - Undergraduate student

Tomer Gabay - Undergraduate student

Yael Ben Aryeh - Undergraduate student

Gili David - MSc student

Victoria Goldin - Amirim student

 

Lab alumni:

Name  /  Degree in the lab  /  Current position
Tal Stern  /  MSc student  /  PhD student in the lab 
Carmit Ginesin-Tzela  /  MSc student  /  Food technologist at Osem 
Riccardo De Leo  /  Internship student  /  PhD student at University of Modena and Reggio Emilia (Italy) 
Dr. Vinayak Ghate / Post doctoral PBC fellow /Food technologist. 
Ronen Bustan / MSc student 
Yael Palman /  MSc student

 

See also: Zvi_Hayouka

Photo Gallery

zvigroup
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aquarium
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Open Positions

 


למעבדה חדשה בקמפוס רחובות


דרושים סטודנטים מצטיינים למאסטר ודוקטוראט למחקר מרתק
שיתמקד בפיתוח חומרים אנטימיקרוביאליים חדשים כנגד בקטריות של מזון

 

נושאי המחקר:

פיתוח אריזות מזון אנטימיקרוביאליות חדשות

תיכנון וסינתזה של חומרים משמרים במזון

פיתוח חומרים אנטיביוטיים המעכבים מסלולי תקשרות שונים בבקטריות של מזון

 

רקע מומלץ:
Organic chemistry, Peptide chemistry, Biochemistry, Molecular biology and Microbiology

להגשת מועמדות או לקבלת פרטים נוספים 
אנא פנו לצביקה חיוקה: 
zvi.hayouka@mail.huji.ac.il

 

 

 
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News

ברכות ליעל פלמן על הזכייה במלגה של מכון שטראוס למחקר

Congratulations to Yael Pelman on receiving the Strauss Institute scholarship

yael-strauss
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See also: Zvi_Hayouka