Jonathan A. McCullers on the Study of Secondary Bacterial Infections
Fast Moving Front Commentary, July 2010
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Article: Insights into the interaction between influenza virus and pneumococcus
Article: Insights into the interaction between influenza
virus and pneumococcus |
Jonathan A. McCullers talks with ScienceWatch.com and answers a few questions about this month's Fast Moving Fronts paper in the field of Microbiology.
Why do you think your paper is highly
cited?
This paper was a review of the state of knowledge about interactions between two important pathogens, influenza virus and Streptococcus pneumoniae. It has been popular and highly cited because of two converging trends—expanding interest in influenza viruses due to the growing threat of a new influenza pandemic, and increased research into the epidemiology and pathogenesis of the great 1918 pandemic (the "Spanish flu").
The recognition that most deaths during the 1918 pandemic stemmed from secondary bacterial pneumonia rather than the virus itself made this manuscript a must-read for those interested in the root causes.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
One interesting thing about study of secondary bacterial infections is that, for the most part, it really isn't very novel at all. The great microbiologists of the first half of the 20th century were intensely interested in this subject and published a great deal of research and some fantastic reviews that, to this day, still frame the current state of our knowledge.
Some time in the middle of the century, study of co-infections fell out of vogue as researchers became more and more specialized and concentrated on single pathogens and host-pathogens interactions in reductionist systems. At the time I wrote this review, we were just beginning to understand some of the molecular underpinnings of the observations made 50-60 years prior, and the material seemed fresh and interesting because of this gap in interest associated with the transformation of science over that time.
Would you summarize the significance of your paper
in layman's terms?
"The recognition that bacterial superinfections account for a great deal of the morbidity and mortality associated with influenza, particularly during pandemics, has led to discussions and recommendations about antibiotic use and stockpiling, as well as bacterial vaccination..."
This manuscript was really a vehicle for me to argue my favored interpretation of the data accumulated over more than a century of study of secondary bacterial infections following influenza. The significance of this work was that this was the first such synthesis of these ideas to be presented in quite some time, and it was published just as scientific interest in this phenomenon began to accelerate.
How did you become involved in this research, and
how would you describe the particular challenges, setbacks, and
successes that you've encountered along the way?
As a postdoctoral fellow in the laboratory of the prominent virologist Dr. Robert Webster in the late 1990s, I was constantly asking him (mostly) unanswerable questions. How this interaction worked was one such question, and he prompted me to explore the subject if I found it interesting.
The research itself has been fascinating and fruitful, without significant setbacks except those that are encountered by everyone who does science in a laboratory. The larger battle was overcoming the inertia of the scientific community which was unused to cross-discipline research such as this.
The narrow siloing of scientists into specialized disciplines (e.g., not just virology, but negative-strand virology) meant that peers, NIH Study Sections, and journal editors didn't know how to handle work that contained elements of virology, bacterial pathogenesis, and innate immunity combined in this fashion. Grants and papers were rejected not on the basis of poor scientific merit, but because they did not fit the standard mold and categories. This has improved through the years as others have gotten involved in similar work.
Where do you see your research leading in the
future?
We are continuing our current approach to understanding viral-bacterial interactions by exploring virulence factors of each independently, but then examining their role in the complex model of two or more infections occurring together or with some temporal relationship. We see two additional areas where this research is leading.
The first is that understanding how these virulence factors differ between strains may give us insight into human epidemiology. For instance, if a particular toxin from Staphylococcus aureuscontributes to fulminant super-infections following influenza, then staphylococcal strains that carry and express this toxin at higher levels than others may be more likely to contribute to human disease.
The second is an expansion beyond the virus-bacteria model to explore other interactions, including virus-virus and bacteria-bacteria interactions, the influence of chronic worm infections on acute viral or bacterial infections, etc. There is a lot to explore within this complex field.
Do you foresee any social or political
implications for your research?
I think our research has been instrumental in driving public policy about pandemic planning. The recognition that bacterial superinfections account for a great deal of the morbidity and mortality associated with influenza, particularly during pandemics, has led to discussions and recommendations about antibiotic use and stockpiling, as well as bacterial vaccination.
As we continue to improve our understanding of the molecular interactions
between pathogens, this should lead to discovery of further interventions
that will change how we prepare for and treat infectious
diseases.
Jonathan A. McCullers, M.D.
Associate Member
Department of Infectious Diseases
St. Jude Children's Research Hospital
Memphis, TN, USA
KEYWORDS: INFLUENZA VIRUS, PNEUMOCOCCUS, INTERACTION, POLYMORPHONUCLEAR LUEKOCYTE DYSFUNCTION, SECONDARY BACTERIAL PNEUMONIA, PLATELET ACTIVATING FACTOR, CHOLINE BINDING PROTEINS, LARGE-SCALE INTERVENTION, TOLL-LIKE RECEPTOR 4, GROWTH FACTOR BETA, ACUTE OTITIS MEDIA, STREPTOCOCCUS PNEUMONIAE.