AZ-17

Phosphate (P) and zinc (Zn) are essential plant nutrients required for nodulation, nitrogen-fixation, plant growth and yield. Mostly applied P and Zn nutrients in the soil are converted into unavailable form. A small number of soil microbes have the ability to transform unsolvable forms of P and Zn to an available form. P-Zn-solubilizing rhizobacteria are potential alternates for P and Zn supplement. In the present study, the effect of two P-Zn-solubilizing bacterial strains (Bacillus sp. strain AZ17 and Pseudomonas sp. strain AZ5) was evaluated on the growth of chickpea plant.

Both strains were purified from the rhizospheric soil of chickpea plant grown-up in sandy soil and rain-fed area (Thal desert). In vitro, both strains solubilize P and Zn as well both strain produce IAA and organic acids. In the field experiments, conducted in the rain-fed area, the positive influence of inoculation with both bacterial isolates AZ5 and AZ17 on chickpea growth was observed.

The application of inoculum (strains AZ5 and AZ17) resulted in up to 17.47% and 17.34% increase in grain yield of both types of chickpea grown in fertilized and non-fertilized soil, respectively over non-inoculated control. Strain AZ5 was the most effective inoculum, increasing up to 17.47%, 16.04%, 26.32%, 22.53%, 26.12% and 22.59% in grain yield, straw weight, nodules number, dry weight of nodules, Zn uptake and P uptake respectively, over control.

These results indicated that Pseudomonas sp. strain AZ5 and Bacillus sp. strain AZ17 can serve as effective microbial inocula for chickpea, particularly in the rain-fed area.

Targeting more than one molecule in multifactorial diseases involving several disease mediators may provide improved therapeutic efficacy. Psoriasis is a multifactorial disease in which interleukin (IL)-6 and IL-23 are important disease mediators because they facilitate development of Th17 cells; widely accepted to be associated with psoriasis. To meet the need for new therapeutics, we aimed to create a clinically relevant bispecific drug, by combining the inhibitory properties of anti-IL-6 and anti-IL-23 antibodies, exhibiting high affinity, high stability and the ability to be produced in high yield. The bispecific molecule AZ17 was created by combining high affinity binding domains originating from monoclonal antibodies targeting human IL-6 and IL-23. To allow for high and efficient production, AZ17 was assembled by site-specific bioconjugation from two individual single chain fragment variables that were synthesized separately in Escherichia coli. To improve stability and extend pharmacokinetics, a flexible poly-ethylene glycol molecule was used as linker. In preclinical psoriasis models, AZ17 reduced IL-23-induced ear inflammation and improved psoriasis in a xenograft transplantation model where psoriasis skin is transplanted onto immune-deficient mice. The data presented here suggest AZ17 to be a promising drug candidate in psoriasis and other inflammatory diseases associated with Th17 cell development.