Recommended Readings: John Mekalanos, Ph.D. October 10

Friday Lecture Series
Friday, October 10, 2014
3:45 p.m., Caspary Auditorium

John Mekalanos, Ph.D.
Adele H. Lehman Professor of Microbiology
Chair, Department of Microbiology and Immunobiology,
Harvard Medical School

The Ghost in the Machine: Understanding Bacterial Secretion Systems Through Defining Their Effectors

Recommended Readings

Empirical Articles

Basler, M., Ho, B. T., & Mekalanos, J. J. (2013). Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell, 152(4), 884–894. doi:10.1016/j.cell.2013.01.042

Basler, M., Pilhofer, M., Henderson, G. P., Jensen, G. J., & Mekalanos, J. J. (2012). Type VI secretion requires a dynamic contractile phage tail-like structure. Nature, 483(7388), 182–186. doi:10.1038/nature10846

Ma, A. T., McAuley, S., Pukatzki, S., & Mekalanos, J. J. (2009). Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells. Cell Host & Microbe, 5(3), 234–243. doi:10.1016/j.chom.2009.02.005

Ma, A. T., & Mekalanos, J. J. (2010). In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system is associated with intestinal inflammation. Proceedings of the National Academy of Sciences, 107(9), 4365–4370. doi:10.1073/pnas.0915156107

Review Papers

Ho, B. T., Dong, T. G., & Mekalanos, J. J. (2014). A view to a kill: the bacterial type VI secretion system. Cell Host & Microbe, 15(1), 9–21. doi:10.1016/j.chom.2013.11.008

British Medical Journal Editorial Outlines Need to Tackle Antibiotic Resistance

Professor Otto Cars from Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, et al. present disturbing evidence that a well-coordinated global response is needed to prevent a pandemic of antibiotic resistance BMJ 2008;337:a1438In the September 18, 2008 publication, Cars unravels a story that began almost eight decades ago when the first antibiotics were used to treat infections.  The use and misuse of antibiotics threatens to take the world back to a pre-antibiotic era with sobering consequences that would impede surgery, organ transplantation, cancer chemotherapy, and a myriad of other healthcare advances.

Low income and middle income countries have poor treatment rates (e.g. 70% of nosocomial neonatal infections could not be successfully treated by using WHO’s recommended regimen).  In high income countries, the number of methicillin resistant Staphylococcus aureus related deaths has increased 30-fold between 1993 and 2006.  To overcome these statistics, the authors call for leadership on international and national levels, changes in consumer and provider behaviors, and better development of effective antibacterial agents to match current need.

The editorial also describes how fundamental problems in sanitation and the lack of safe water contribute to the overuse of antibiotics as a quick-fix solution to avoid disease.  And as existing antibiotics decline in their effectiveness, the discovery of new antibiotics is also declining.  Innovation and the discovery of new antibacterial agents has been meager in recent years; less than 2% of all drugs in development at the world’s largest pharmaceutical companies are antibiotics and there still remains unmet needs for treating some Gram negative infections.

Summary points listed in the article include:

  • “Antibiotics are a prerequisite for many of the advanced technologies in today’s healthcare”
  • “Although antibacterial resistance is growing, development of new antibiotics has declined”
  • “A new paradigm in which antibiotics are considered as a non-renewable resource is needed”
  • “The know-do gap in control of bacterial resistance to antibioticsmust be tackled on international, national, and individual levels”