Anti-infection Group

The research of Anti-infection Group is focused on identification of bioactive metabolites from our microbial natural product libraries by whole cell and organism screening approaches combined with protein target-based assays.

Whole cell screening approaches

1. Many drugs could be more effective at a reduced dosage if low dosages of other synergistic compounds are introduced simultaneously. This synergistic premise offers a way of resurrecting drugs whose patents are expiring or rescuing drug candidates abandoned because of inadequate safety profiles. One of our works is using whole cell approaches to screening synergistic medicines and to identify novel anti-fungal synergistic drugs.
2. We have developed a comprehensive robust drug-screening assay to identify anti-tubercular hits among naturally derived products. The assay utilizes constitutive GFP expression with direct readout of fluorescence as a measure of bacterial growth in a 384-well format.
3. As Mtb resides primarily in the macrophage where it is able to survive and replicate, we need to examine the activity of “novel drugs” using macrophage model of infection.

Target based screening

We are interested in identifying inhibitors against two kinases (PknB and PknG) and one phosphatase (PtpA). PknB, earlier shown to be essential for Mtb growth; PknG which is required for Mtb growth in animals and PtpA which we identified to be essential for Mtb pathogenicity within human macrophages as it interferes with the signal transduction pathway of the host macrophage.

Whole animal model based screening

We developed a Caenorhabditis elegans - bacterial infection assay in collaboration with Prof. Frederick M Ausubel for mining novel antibacterial compounds from our proprietary natural product libraries. The use of C. elegans as a whole animal infection model allows screening of small molecules that cure infected worms not only by killing the pathogen, but also by inhibiting its virulence or boosting the host immunity intermediated by the host-pathogen interaction. In comparison to traditional antibiotics, the discovery of these novel antimicrobial compounds such as anti-virulence agents and immune-modulators may mitigate the spread of antibiotic resistance, as they would not target mechanisms which were subject to selective pressure in the environment that commonly lead to drug resistances.

Selected Publications

Research