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.

Zvi_Hayouka

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.

Zvi_Hayouka

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.