A group of Indian scientists has, for the first time, completely mapped the genome for a bacterium, which is the forefather of a malicious strain of bacterial species that causes bladder cancer, psoriasis and weakens the immunity system of HIV/AIDS patients.
“It’s a harmless, helpful bacterium and so we were surprised when we discovered that it was the direct ancestor to a major group of lethal members of the mycobacterium family,” said Seyed Has-nain, a scientist involved with the sequencing.
The scientists claim that their effort in mapping the genome of the Mycobacterium indicus pranii (MIP), a bacterium now used as a leprosy vaccine in India, and establishing the lineage with the dangerous family of bacteria called Mycobacterium avium intracellulare complex (Maic), would help researchers design drugs that target its criminal genes.
Maic is also known to cause the fatal Johne’s disease, which targets cattle worldwide, and has been implicated as a cause of Crohn’s disease, a painful, non-fatal disease that affects the human digestive system.
The research team sequencing the genome, which consists of six million base pairs or the building blocks that make the gene, comprised scientists from the government-funded Centre for DNA Fingerprinting and Diagnostics, and the University of Delhi.
They published their findings in a recent issue of the PLoS One, a peer-reviewed journal.
The only major genome sequencing effort in the public domain involving India has been the International Rice Genome Sequencing Project, which involved the UK, the US, Japan, South Korea, Brazil, Thailand and France.
Though a range of anti-bacterial drugs from ciprofloxacin to azithromycin are used for treating these diseases, Maic mutates rapidly and frequently outsmart the drugs, like their best-known relative, the Mycobacterium tuberculosis, which causes tuberculosis in human beings and is known to frequently develop drug-resistant strains.
MIP, which is commercially marketed as a leprosy vaccine—Immuvac—by Cadila Pharmaceuticals Ltd, is also being tested for a wide range of drugs for HIV/AIDS, psoriasis and bladder cancer, because of its therapeutic effects on the immune system.
Unlike human reproduction, where children inherit an equal amount of genetic material from both parents, mycobacteria, like most bacteria, propagate by cloning. Each daughter cell thus has a duplicate copy of the entire genetic material of its parent, which makes it relatively easier to trace the lineage of each gene.
“Now since we have the genetic code of both the parent and the descendant, we can know how, and which genes of the benign ancestor, mutated to become the deadly genes in the later generation,” said Akhilesh Tyagi of the Delhi University, a member of the team.
Once these genes are identified, drugs can be designed to target these locations, an approach in drug design called gene targeting, which earned scientists Mario Cappechi, Oliver Smithies and Martin Evans the 2007 Nobel Prize for medicine.
Though the rice genome consists of 400 million base pairs and the human genome 3,000 million pairs, mapping the six-million base pair MIP genome “was also hard work”, Tyagi said.
“Yes, genome sequencing projects are the trend now,” said a senior scientist in the government’s department of biotechnology, requesting anonymity.
“We missed the bus on the human genome project, and today, when scientists are creating chromosomes, we are still at elementary sequencing stages. But nevertheless, some progress is being made,” the scientist added.
But the man who first isolated the MIP bacilli and proved that it could be used as a vaccine, G.P. Talwar, who heads the Talwar Research Foundation here, said, “The MIP has always been a friendly bacterium, but I haven’t seen the sequencing analysis yet.
“However, I think the biggest benefit of completely mapping any genome is that it reveals possible new applications of an organism.”