Wednesday, 1 February 2012

Middle of the Road Pays for Pathogens

To understand why infectious diseases make us ill, it helps to consider disease from the pathogen’s point of view. Bacteria, viruses and parasites did not evolve simply to cause illness and suffering; virulence is simply a by-product of a pathogen’s fight for survival. Because an infectious agent which incapacitates its host before it has had the chance to be transmitted is an evolutionary dead-end, the key factor for survival is in striking the correct balance between transmissibility and virulence. It's a numbers game—a pathogen needs to divide in sufficient numbers to overcome the efforts of the host’s immune system long enough to ensure that it will be transmitted to a new host. But exploit the host too much, and there is the risk that the pathogen will be left homeless.

Pathogens have evolved various solutions to this paradoxical situation. Mycobacterium tuberculosis, the bacterium responsible for TB, has been infecting humans for thousands of years and it has evolved to be extremely good at it. Because this disease first emerged when we lived in isolated communities, M. tuberculosis became adept at asymptomatically infecting as many people as possible for extremely long periods of time, causing active disease in only a proportion of those infected. In this way, M. tuberculosis ensured its prehistoric hosts would survive long enough to encounter other humans to which they could spread the disease.

The waiting game works for pathogens like M. tuberculosis, where close contact between hosts is required for transmission. But a disease such as malaria which is spread by a secondary vector can afford to make the host much sicker and still guarantee the infection can be passed on to others. Diarrheal diseases such as cholera can be similarly highly virulent. In this case, the infection is spread via contaminated water, meaning that the bacterium responsible can be transmitted even when it replicates in the host at such high levels that they rapidly succumb to the infection and die.

Thinking about how pathogens evolve to ensure their own survival led me to this recent paper published in Scientific Reports. This work is interesting in that the authors consider the role of host evolution as well as that of the pathogen in determining disease outcome. In the case of highly virulent infectious agents, is the rapid death of the host something which might be beneficial to a population on the whole?

The idea behind this hypothesis is that, if a member of the host population dies immediately upon infection, they can protect the rest of the population from secondary infections. The team from the University of Tokyo investigated the infection of Escherichia coli with a bacteriophage lambda. They used a mixed population of E. coli containing an altruistic host, which commits a bacterial version of suicide as soon as it is infected, and a susceptible host, which permits multiplication and transmission of the phage. When these strains were infected in a structured habitat in which contact between hosts was limited to close neighbours, the presence of the altruistic hosts protected the overall population from being overcome by the infection.

The researchers also observed the emergence of phage mutants that could bypass the altruistic host suicide mechanism. By not killing the host, these random mutants ensured that they could be passed on to other bacterial cells and guaranteed their own survival.

Presence of altruistic hosts which commit suicide upon infection protects entire population including susceptible hosts

This work demonstrates that virulence has not evolved as a result of the pathogen alone, but is influenced by the interaction between the host and the pathogen. In a way, this represents an ‘arms race between pathogen infectivity and host resistance.’ The pathogen will favour lower virulence in order to maintain a sustainable symbiosis, while the host population as a whole benefits from high virulence even though individuals die as a result.

Suicidal defence has previously been described in multi-cellular organisms, where infected single cells are rapidly destroyed to prevent spread of the infectious agent throughout the entire organism. Taking these findings and attempting to extrapolate the data to make conclusions about how human evolution has shaped pathogen virulence is perhaps taking things too far. The huge difference in the growth rates of a human and a bacterium means that the majority of the evolutionary contribution to this particular arms race is from the bacterium’s side. However, this kind of study does show that, where the survival of two organisms is so intertwined, we cannot consider one without taking the involvement of the other into account.

Evolution may move too slowly for humans to compete with pathogens in this way, but the environmental changes that we make have a huge impact on the ability of bacteria and viruses to infect us. This has already been observed in the case of cholera. As improvements in sanitation become more widespread, highly virulent strains are disappearing. This is because those strains which incapacitate the host very rapidly can no longer be as easily passed on, meaning that less virulent strains that do not kill so quickly have the advantage.

It is also interesting to think about how our modern way of life can contribute towards creating epidemics. For example, the bird flu threat would not be quite so concerning if it wasn’t for air-travel providing the potential for any emerging epidemic to spread around the entire world. A highly virulent pathogen is likely to be fairly short-lived unless it has a way to spread very rapidly to a large number of hosts. Take Ebola for example—one of the world’s most deadly diseases, yet outbreaks can be confined to relatively small areas and burn out quickly. In this regard, Ebola is actually a fairly unsuccessful pathogen. M tuberculosis, on the other hand, remains a global issue predominantly due to its ability to infect a huge proportion of the population without causing rapid death of the host. In this case, patience can pay off for a pathogen.

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