How did I become interested in Mtb? What do I study?
I was interested in studying bacteria when I started my PhD program. During my lab rotations, I found that the scale of the questions in mycobacterial research is different than I had seen before.
Mycobacteriologists ask questions about individual cells- how does the individual respond compared to the whole population. I loved the thought that the individual matters! This has important implications in treating Mtb, a disease where a single bacterium can cause an infection, and outcomes of infection are variable.
The scale of questions is so dynamic-- “what is the function of residue XY or Z in protein A?”, “How come some people never get TB disease even though they harbor the bacteria?”, “How does treatment work if Mtb goes dormant?”, “How do these bacteria grow and divide?”
I joined the Rubin lab and began studying peptidoglycan (PG), the essential first layer of the bacterial cell wall. Why do we care about PG in Mtb? The current first line Mtb drugs we have target other layers of the cell wall, but the classical antibiotics, beta-lactams like penicillin, were long thought to be inactive against Mtb. So, PG hasn’t been seen as a drug target in Mtb until recently. It is now known beta-lactams can actually kill Mtb when used in combination with other drugs. If we can understand how Mtb builds its cell wall, we can start to design and combine drugs to subvert the process.
What is it like working with Mtb?
Besides the time it takes for Mtb to double (~24 hours), one cannot simply hop into lab and start an experiment- you have to be specially trained and you have to suit up. And I’m not talking about herringbone 3 piece suits here. I mean suit up in PPE (personal protective equipment)-tyvek suit, booties, tyvek sleeves, respirators with batteries and filters, double gloves… (see photo). Working in a biosafety level 3 is challenging, but it also creates a community based around teamwork. I've really enjoyed the camaraderie it fosters.
What do you think is the biggest challenge today for successfully eradicating TB?
I’m not an expert in TB eradication by any means, but I think the sheer number of people harboring the bacteria in latent infections poses a large challenge in eradication TB. What is Mtb doing during a latent infection? Can we target this stage? The more we understand on a basic level about Mtb, the more thoughtfully we can target it.
What would I like the public to appreciate about Mtb?
It’s a weirdo bacterium. What kind of bacterium only doubles every ~24hours? Is it just so lazy? Is its cell wall so intricate that it has to unravel all its layers and knit them all back together every cell division?
Mtb has been residing in human lungs for forever – probably since humans have been a thing - (don’t cite me on this, but it seems like mummies are always being found to have TB) and yet this bacterium is still widespread. We are beginning to understand on a molecular level some of Mtb’s secrets, but we still have a long road ahead. It is definitely not a disease of the past, but hopefully it will be one day soon.
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