Immunology and microbiology come together to fight disease.
It is hardly surprising that scientific papers on human pathogens are often peppered with military analogies. Traditionally, the study of infectious disease has been considered as a conflict in which pathogens are the enemy, to be sought out and destroyed. The success of antibiotics in the twentieth century reinforced the notion that infectious diseases could be defeated, if only we could find enough ways to kill the microbes that cause them.
Battles still need to be fought, and the report in this issue of the discovery of a potentially new class of antibiotic (see pages 293 and 358) may yield some valuable new weapons. But outright victory looks increasing unlikely. A surge in strains of resistant bacteria — such as methicillin-resistant Staphylococcus aureus (MRSA) — means that an increasing number of bacterial infections cannot be treated effectively. And the growth in the number of emerging infectious diseases means that the problem is likely to get bigger.
All this is compounded by the withdrawal of many major drug companies from research into antibiotics, and the long timescale for developing new ones (see page 260). Furthermore, persisting in an arms race against microbial resistance may prove futile: it is a race that bacteria are well equipped to win, having evolved mechanisms over millions of years that help them develop resistance to molecules secreted by competing microbes.
Many in the microbiology and immunology communities now believe there is a need for radical new strategies in fighting infectious disease. Developments in immunology and other fields are prompting a convergence towards a more holistic approach that takes into account the complex set of feedback loops between pathogens, host immune systems and our own microbiota.
Better understanding of the host–pathogen interactions at the molecular level may yield answers and open up new ways of thinking about pathogenesis. Rather than always seeking to kill bacteria, for example, molecules that slow their growth or spread may be enough to let the host microbiota and immune system outcompete them, particularly if ways can be found to stimulate or modulate either. Molecules that harnessed our own defences against pathogens would also have the benefit of being less selective for resistance.
Take, for example, Mycobacterium tuberculosis, the bacterium that causes tuberculosis. It infects one in ten people in North America and Western Europe, and one in three worldwide, but only a fraction of these will develop the full-blown disease, with the bacterium dormant or kept in check in the remainder. What tips the balance towards disease? As yet, we have little idea.
Our understanding of the ecology of our own microbiota is limited, as is the molecular basis of host immunity in response to infection. There is still much to understand — until recently, for example, scientists paid little heed to innate immunity, comprising immune cells and secreted molecules that react immediately but rather non-specifically to pathogens. It has only recently been discovered to be much more complex and active than was previously thought.
Such ideas are outlined in an excellent US National Academies report, Treating Infectious Diseases in a Microbial World (see http://fermat.nap.edu/catalog/11471.html). Infectious diseases have for too long been considered either from the point of view of the microbiologist, with a focus on the pathogen, or from the point of view of the immunologist, with a focus on the host. Basic microbiology, which has lately struggled to win support against competing fields, must not be neglected. But research agencies, universities and scientists should embrace approaches that unite microbiologists and immunologists in the study of infection biology.
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epiPATH: an information system for the storage and management of molecular epidemiology data from infectious pathogens
BMC Infectious Diseases (2007)