Lalita Ramakrishnan (Cambridge) 1: Tuberculosis: The Pathogenic Personality of the Tubercle bacillus

Lalita Ramakrishnan gives an introduction to tuberculosis (TB) pathogenesis, gives an overview of Mycobacterium tuberculosis’ life cycle, and explains how the TB bacteria gain entry into the host.
Part 1: An Introduction to Tuberculosis: The Pathogenic Personality of the Tubercle bacillus: Lalita Ramakrishnan gives an introduction to tuberculosis (TB) pathogenesis, and gives an overview of Mycobacterium tuberculosis’ life cycle.
Part 2: The Troublesome Tubercle in Tuberculosis: After the tuberculosis (TB) bacteria infect macrophages, a complex structure called a granuloma develops. Ramakrishnan explains how her laboratory used a zebrafish model of TB to study the involvement of granulomas in TB progression.
Part 3: Tuberculosis as an Inflammatory Disease: Lalita Ramakrishnan’s laboratory has studied the molecular pathogenesis of TB using the power of forward genetics in the zebrafish.
Talk Overview:
In this seminar, Dr. Lalita Ramakrishnan gives an introduction to tuberculosis (TB) pathogenesis, and gives an overview of Mycobacterium tuberculosis’ life cycle. She explains how the TB bacteria gain entry into the host by using specific lipids to avoid microbicidal macrophages and recruit growth-permissive ones. Once inside the macrophage, the bacteria use multiple virulence genes to survive intracellularly. In particular, Ramakrishnan discusses bacterial efflux pumps that, in addition to promoting intracellular survival, also induce tolerance to multiple antibiotics. Most individuals have effective counterstrategies so that they are able to clear TB infection by a combination of innate and adaptive immunity. Yet scientists have not been able to understand these defense strategies enough to harness them and create an effective vaccine against TB.
After the TB bacteria infect macrophages, a complex structure called a granuloma develops. Different immune cells arrive at the granuloma to surround the bacterial infection and fight the disease. In her second lecture, Ramakrishnan explains how her laboratory used a zebrafish model of TB to study the involvement of granulomas in TB progression. Although granulomas were thought to constrain infection, her laboratory showed that the bacteria hijack the granulomas to spread the disease. For example, Ramakrishnan showed that TB bacteria promote the recruitment of new macrophages to the granuloma that engulf dying infected macrophages to expand infection.
Ramakrishnan’s laboratory has studied the molecular pathogenesis of TB using the power of forward genetics in the zebrafish. They discovered that mutations in LTA4H, a key enzyme in the eicosanoid pathway that alters the levels of the cytokine tumor necrosis factor (TNF), affect tuberculosis pathogenesis by regulating the inflammatory response. This work showed that a balance of TNF is required for good TB prognosis, and neither high nor low inflammation was favorable. Correspondingly, they showed that genetic variation in LTA4H in humans helps explain patterns of TB meningitis survival when patients were exposed to a treatment that suppresses the inflammatory response.
Speaker Biography:
Dr. Lalita Ramakrishnan is a professor of immunology and infectious diseases at the University of Cambridge, UK. She received her medical degree from the Baroda Medical College in India, and her PhD in Immunology from Tufts University in Boston. After completing her medical residency at Tufts and a fellowship in Infectious Diseases at the University of California, San Francisco, she joined the lab of Dr. Stanley Falkow at Stanford University as a postdoctoral fellow. There she developed Mycobacterium marinum as a model for to study tuberculosis pathogenesis. She then joined the faculty at the University of Washington, where her laboratory developed the zebrafish infected with M. marinum as a model for tuberculosis. In 2014, she moved to the University of Cambridge, where her laboratory continues to unravel the molecular underpinnings of TB pathogenesis.
Ramakrishnan’s work has been recognized with several awards and honors, including the NIH Director’s Pioneer Award, the Wellcome Trust Principal Research Fellowship and election to the US National Academy of Sciences (2015). Learn more about Ramakrishnan’s research here: www.med.cam.ac.uk/ramakrishnan/

[@leonelemiliolereboursnadal6966]

Dr Lalita, you are now in my list of real super heroes! One of the best presentation about any medical topic that I ever seen. So much passion! Thanks for posting this video

[@alexnicklen5379]

This is a fantastic lecture. Some of this knowledge is extremely difficult to teach, but you do it wonderfully!

[@lavkumar420]

Thank you Dr. Lalita. I am suffering from TB although I am a very healthy individual otherwise. This presentation of yours helped me understand the mechanism of TB infection without using complex biological jargon.

[@phathong7980]

igrotum - the silver lining in my tuberculosis journey. Seeing real improvements and feeling better.

[@usernya_anin37]

igrotum is a beacon of hope for those facing tuberculosis challenges. Its making a real difference.

[@jenniferprudhomme9399]

i learned a new thing And you helped me alot on my project about TB! YOU GAVE ME GOOD IDEAS

[@rajooananth4719]

excellent presentation -

[@zakirzak1494]

You are very good at teaching, thank you

[@Niazi-uq1gy]

Tuberculosis may be persistent, but igrotum is equally resilient. Positive changes on the horizon.

[@kkkx262]

igrotum is my go-to solution for tuberculosis. Witnessing improvement and regaining strength.

[@gringopapi6985]

Very well explained

[@masterscience9490]

mind blowing explanation

[@aftabmmansuri1576]

Mam Feeling Proud as Our Indian Representating the worlds one of the top universities..cambridge BLESSING FROM INDIA

[@pinrani98794]

Very nice presentation

[@markotomasevic8028]

Superb lecture, thanks!

[@Pammutiwari007]

Namaste

[@mmoussa]

Great presentation. Please tell us about the new vaccine that just came out in NATURE magazine.

[@catherinevanegas8181]

What is the vaccine called

[@alialsalami7934]

Thank you so much

[@shahidKhan-jf7op]

Good lalita madam

[@osmosis8160]

This is the actual product of India, which India never under estimated....currently they are serving foreign nations

[@beckysegundo6688]

Great lecture but poor bunnies.

[@StephenGillie]

Mycobacterium Tuberculosis evolved 60 ky before biblical Abraham, indeed likely after the evolution of humans. Villemin and Koch found the bacterium the same year as FDR was born, 2 years after Edison began production of carbon filament light bulbs, 4 years before the Harvard observatory sighted Barnard's Star, and a decade before the Barnard sees the 5th moon of Jupiter.