Novel ‘replication check mechanism’ key to dormant Tuberculosis

Tuberculosis is a major communicable disease expanding globally and is caused by Mycobacterium tuberculosis (M. tb). The disease is a main killer among infectious diseases in the world with the occurrence of 2 million deaths each year and 8 million cases of active disease. The biggest challenge of tuberculosis (TB) is its ability to survive in dormant form in apparently healthy individuals for decades. M.tb, the diehard pathogen that causes tuberculosis, is capable of staying asymptomatically in a latent form, persisting for years in very low replicating state, before getting reactivated to cause active infection.

M.tb is known to survive for extended periods during the latency phase without any replication. During this phase the bacterium senses the surrounding environmental conditions such as availability of nutrients, immune cell preponderance etc. and if needed puts its machinery back in action to grow and replicate. The regulation of chromosomal DNA replication therefore is a very important switch to maintain dormancy. While the bacterium is dormant replication is bare minimum.

A new study published by PLoS ONE (In-vitro helix opening of M. tuberculosis oriC by DnaA occurs at precise location and is inhibited by IciA like protein) provides some fresh insights into maintenance of dormancy by the pathogenic mycobacteria. Professor Seyed E. Hasnain (Distinguished Professor at the Institute of Life Sciences at the Hyderabad University campus, Hyderabad, India) who led the study said ‘the dormant state of the bacterium is maintained by a novel protein called as Inhibitor of Chromosomal initiation (IciA), which our group has rigorously characterized and which binds to the A+T rich region of the origin of replication’. ‘This binding blocks helix opening of the A+T rich region, a step critical for chromosomal replication initiation to occur’ says Hasnain. This represents the first evidence that chromosomal DNA replication control is a critical molecular switch in the form of IciA protein, which the TB bacteria over express to remain dormant.

Besides identification of the replication check phenomenon by the IciA, the study also generated an in vitro model of mycobacterial replication which will be a very important tool in the hands of infection biologists trying to understand intricacies of microbial acquisition, survival and adaptation under different stress conditions and in different hosts. Although the present study largely represents laboratory based observations, direct evidence for the role of the IciA like protein will come from M.tb iciA knockout experiments to be performed in an animal infection model. While such experiments are underway at Hasnain labs, it will be interesting to see if quantitative expression of IciA in tuberculosis patient’s material could effectively be harnessed as a molecular marker of M.tb activation.

Songs that thronged PLoS ONE through 2008

Well, we listened a lot to bird songs last year at PLoS ONE forums and journal clubs. After birds, mice arrived on the scene to sing and squeal, meaning that rodents could as well joyfully sing, and that their songs to prospective mates are as likely complex as those of birds. However, unlike birds, their vocalizations are discharged at ultrasonic frequencies, and that is why no one noticed them, nor was anyone motivated to celebrate them. But, as one of the many celebrated PLoS ONE stories (DOI: 10.1371/journal.pone.0001893) echoes in popular media and blogosphere, we may hope they will likely find a place in romantic poetry! The article was published by H. Wang and colleagues quite some time back (in April 2008), but was recently showcased in a recent news round-up by New Scientist of the top ten genetics stories of the year. Alison Motluk of New Scientist discussed this research and also provided recordings of the squeaks of male mice in a human audible format.

“Most musical, most melancholy bird,” said Samuel Taylor Coleridge of the nightingale ‘but whether birdsong can affect us in the same way as a beautiful sonata played by a human musician is another matter’ said Rebecca Walton in her blog post summating another celebrated article by Stefan Koelsch of the University of Sussex, wherein his team, investigated differential response to instrumental and computerised music. According to this research, volunteers who listened to recordings of professional pianists showed more emotional activity of the brain than did those who listened to recordings made by computer. This article was covered in different headlines by the Chronicle of Higher Education (Don't Cry For Me, R2D2), The Telegraph (Sweaty music find could help develop new treatments), The Guardian (Music that brings a tear to the eye), Wired (Study: Computer Musicians Ain't Got No Soul) and PsychCentral (Computer Music Not As Calming).

At the end of the year, one more article ("Practicing a musical instrument in childhood is associated with enhanced verbal ability and nonverbal reasoning" PLoS ONE, 2008) dominated the blogosphere, this time for another reason, to celebrate the second birthday of PLoS ONE! This was all about an excellent blog by SciCurious of the Neurotopia 2.0 (Einstein was smart, but Could He Play the Violin?) who won the PLoS ONE second birthday synchroblogging competition organized on December 20, 2008.

All content published in PLoS ONE, from dinosaurs to elephants to chimps to birds to bats and about mice to butterflies and bees is freely available online. Rate them and comment and discuss yourself to enjoy the full power of Web 2.0 technology that PLoS ONE harnesses. Here at PLoS ONE is certainly quite diverse food for thought and you can always join in the discussion by creating an account on the journal site and posting your comments for others to read.