Research

ssRNA phage and
Single-Gene Lysis

“DISCOVERY IS THE WAY” – ssRNA phages have been largely ignored by phage scientists. There is a lack of understanding regarding the diversity, host range and evolution of ssRNA phages. These small viruses, measuring less than 40 nm and with a genome of 3.2-4.5 kb, have only four genes, one of which encodes a lysis protein. The lysis protein is named SGL (Single-Gene Lysis). Also using metagenomic mining to identify sgl’s in metatranscriptomics data from around the globe. Exploring the targets of these SGLs in the peptidoglycan pathway may lead to the discovery of ‘new protein antibiotics’.

Source: JBC.org

Single-Gene Lysis: Protein E of ssDNA phage phiX174 causes septal cell blebbing and lysis.

Phage Biology

My research revolves around the study of bacteriophages, which are highly abundant on Earth and have the potential to combat bacterial infections. Specifically, it is dedicated to identifying phages that can infect a wide range of host species and uncovering their diverse nature. I have published several papers discussing various aspects of phage biology, including their morphology, genetics & genomics, and phage-antibiotic synergy. One of my main interests lies in understanding the functions of phage proteins and exploring their anti-biofilm potential (dual-species biofilms). Moreover, I am actively designing combinations of phages (cocktails) to kill multi-bacterial infections. Currently investigating the phage receptors of Chi-like flagellotropic phages.


Phage Lysis System

“ONLY WAY OUT IS THROUGH” – Any dsDNA bacteriophage uses a combination of genes, called a multi-gene lysis system, to break open each layer in the bacterial membrane to escape the cell. These genes include holin, endolysin, and spanin (up to seven genes are known to control lysis), which effectively break down and destroy the different layers in the bacterial cell (from within). My research uses single-cell imaging to monitor the multi-gene lysis. The combinations of genes may be holin (-antiholin), endolysin and i/o-spanin [or] pin-holin, SAR-endolysin and u-spanin. The interest is also towards identifying the functional endolysins (late genes) in phage genomes and to differentiate them from other LPS-degrading enzymes (early genes).

Phage lysis proteins: This is one of the most interesting phenotypes in biology. Without spanins, the E. coli lysogens become spherical. Pic: Lambda lysogens with holin (S), endolysin (R), and lack spanins (Rz/Rz1).

A spinning bug model to study the phage lysis. By monitoring the pmf collapse, it is possible to visualize the lysis at the single-cell level.

Phage Therapy

Antibiotic resistance is a major healthcare problem, with a projected 10 million deaths by 2050. It emphasizes the need for thorough monitoring and exploration of alternative treatments, such as the use of live bacteriophages to treat antibiotic-resistant bacterial infections. The research involves developing phage banks to study, store, and distribute therapeutic phages, as well as designing phage cocktails to eliminate bacterial infections. The targets are mostly clinical pathogens such as E. coli, Klebsiella pneumoniae, Enterobacter sp., Acinetobacter baumannii, S. aureus, Pseudomonas aeruginosa and Proteus mirabilis.