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Rosie enrolled for the Cambridge Immerse Biology Programme in 2015. She is now studying Natural Sciences at Emmanuel College, University of Cambridge.

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Humans seem to be in a race with viruses, bacteria, fungi and parasites to create new drugs to combat infections before they evolve to overcome them.

Antibiotic resistance is becoming a worrying problem. The first antibiotic, penicillin, was discovered by accident by Alexander Fleming in 1928.

This started to be used to treat Staphylococcus bacterial infections in humans in 1932 – at this time, there were no known resistant bacteria. However, by 1950 40% of all Staphylococci bacteria had become resistant and this number increased to 80% by 1960. At this point another antibiotic, methicillin started to be used (a relative of penicillin). Once again, within two years the first incident of methicillin-resistant Staphylococcus aureus (MRSA) bacteria was recorded. MRSA is now present in almost all hospitals across the world and infection can be lethal. Treatment has now moved to a different class of antibiotics including drugs such as vancomycin. The first case of vancomycin-resistant Staphylococcus aureus bacteria was recorded in 1996.

This is not just a problem in treating bacterial infections.  Pathogens are any organism that can cause disease. This can include bacteria, viruses, fungi and parasites. We are constantly having to come up with new drugs to combat any pathogen’s infections as they rapidly evolve to become resistant.

This arms race between humans and pathogens sounds frightening – how can we keep up with their rate of evolution to avoid our drugs? Will we one day run out of ideas and be unable to treat infections at all? Paul Ewald, an expert in the field of the evolution of infectious diseases thinks we need to take a different strategy.

 The bacteria are faster than us, but we are smarter. What if we were able to alter the way pathogens evolved to make them less virulent (harmful)? If we somehow make it easier for a given type of pathogen to survive in a healthy human, rather than a sick one, then we might drive the evolution of the pathogen to make it less virulent.

The biological imperatives of life are to survive and reproduce. For pathogens, it is necessary to be inside a host to do this. Once it has replicated as much as it can in one host, it must somehow jump to another host so that it can continue replicating.

Let us consider the different ways in which a pathogen can be transmitted from person to person:

  1. Close proximity to people – can spread through air or physical contact – e.g. HIV, rhinovirus (causes the common cold), influenza
  2. Hitching a ride on an intermediate organism – e.g. Plasmodium (the parasite that causes malaria) in mosquitoes
  3. Travelling through contaminated water – e.g. cholera  

In the first category, it is not in the pathogen’s interest to be too virulent. If they kill the host, then it will not spread to another human. Pathogens with a mild virulence are selected for in this category as this ensures that the host can move around and encounter lots of other people. For example, if you have a cold, you are not so ill that you have to stay at home – instead, you go to school/ work and cough on everyone you meet – passing the bacteria/ virus to them. Pathogens in this category are therefore very unlikely to evolve to become lethal as this would be strongly selected against.

In contrast, pathogens that rely on an intermediate organism to ensure their transmission do not have to worry about keeping the host mobile. Instead, they incapacitate you to ensure better access for the intermediate organisms (often mosquitoes) to bite you. For example, malaria makes you feel so unwell that you have to lie in bed all day – this makes you the prime target for other mosquitoes. The parasite that causes malaria, Plasmodium, is then ingested by the mosquito as it drinks your blood. That mosquito will then infect everyone else that it bites. In this category, there is an evolutionary advantage to push you to the brink of death.

Pathogens that don’t need to rely on any organism to ensure their transmission can be even more virulent. There is no need at all for the host to be mobile and therefore the only selection pressure is to replicate as many times as possible to increase the probability of future infection. These pathogens often rely on contaminated food/ water supplies. Vibrio cholera bacteria cause terrible diarrhoea and spread through unprotected water supplies. When soiled bed linens/ clothes are washed in rivers or lakes, the bacteria in the diarrhoea can be released into a drinking water supply.  There is actually an advantage for cholera to evolve to be more virulent as causing more diarrhoea results in more copies of the bacteria leaving the body and therefore increases the likelihood of infecting someone else.

Understanding the evolutionary pressures in each of these categories helps us to understand ways in which we might manipulate the evolution of the pathogens to become less virulent. In the example of malaria, there is a selective pressure for a virulence that ensures the host is incapacitated to make them more accessible for other mosquitoes. If, however, when the person is incapacitated, they were surrounded by a mosquito net, the mosquitoes would be unable to access them. The selection pressure would then shift to favour Plasmodium that did not cause as much harm and so means that the host feels well enough to move around. This would then make them accessible to other mosquitoes to spread the disease, but it would decrease the virulence of malaria significantly.

If the water systems are cleared up so that they don’t get contaminated, cholera bacteria would have to become less virulent so the person could transfer it around by other means. This theory has been backed up with evidence. In 1991 there were a series of cholera outbreaks across South and Central America. The quality of the water systems in these countries varied considerably. It was found that in regions with poor water supplies the bacteria had evolved to be significantly more virulent than those found in places with clean, safe water supplies. 

So, can we use our understanding to change the evolution of all pathogens away from virulence? If you shut down the modes of transmission that don’t require human participation, suddenly all the evolutionary pressure is directed at allowing the human to get up and about to find a new host. There is, however, an exception to this rule. Pathogens that can survive for a long time outside of a host are less concerned with evolutionary pressures regarding transmission and we are therefore unlikely to be able to change their evolutionary path by controlling their transmission.

The implications of this are huge. Instead of challenging the bacteria to become stronger and more dangerous, we can challenge them to get along with us. Controlling the transmission of pathogens is not a new concept – we all know we should cover our mouths when we cough. However, this approach is not aiming to prevent the spread of the diseases, but rather to make those diseases much less harmful.

 

Source: survival of the sickest: the surprising connection between disease and longevity – by Dr Sharon Moalem

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