My Banter with Pathogens

There are trillions of bacteria on and in your body right now and they’re talking to each other…about you. A statement said on a park bench or in the pub might be passed off as madness or at least make you want to switch seats, but in the lab, it is serious research.

Life relies on communication. Bird songs, for example, may be pleasurable to our ears but the birds do not call for us. You’d be forgiven for thinking that social lives are the domain of animals and plants and the life that we can see. This would be a mistake; microbiologists are finding increasingly that bacteria have social lives that would make any aspiring debutante jealous.

Bacteria do not act as lone wolfs; they interact with each other, passing notes, organising themselves. They act as one large group, able to overcome problems with sheer numbers; problems like our immune systems. The social life of a bacterium is generally controlled by small chemical molecules, which they release and build up in the environment. This environment can be the soil, the Petri dish or even the lung of a patient suffering from cystic fibrosis. This process is known to biologists as ‘quorum sensing’. The term comes from the legal world in which a ‘quorum’ is the minimal number of members required to reach an agreement that is representative of the total number of members. Outside confusing jargon, a quorum is the smallest a group of representatives can be to still act and make decisions in a legitimate way.

The social activities of some bacteria are not as passive as the warble of a swan. Bacteria use these chemicals to scheme and plot against you in a clandestine manner. Your body is constantly looking for foreign intruders which it will try to destroy. The problem your immune system has is deciding what is ‘natural flora’ and what is a ‘pathogen’. Pathogens use a range of tools called virulence factors to overcome your immune system and make you unwell. The immune system has evolved to recognise these bacterial tools as a way to identify the ‘good’ bacteria from the nasty critters.

However, some pathogens have learnt to use the social network to control when they make and express their invasion tools. Once the quorum sensing chemicals have built up to a sufficient level, they cause the genes of the virulence factors to be expressed and by the time this happens, the bacteria have multiplied to a large number.  All of a sudden your immune system is faced with a massive horde of pathogenic bacteria. The following analogy might express the tactics of bacteria better: imagine your immune system is an army within a castle; it keeps watch over the walls and sees a large number of peaceful-looking people going about their day-to-day lives. This is the natural flora in your body and then, out of nowhere, this sea of people become an invading army, pulling out weapons and charging the keep.

Severe illness can be thought of as the immune system failing or struggling to fight off an infection. Thus, by timing when they become a threat, bacteria can get the advantage over their host. I must say that this tactic is not isolated to a few bacteria that have become savvy and spotted a clever way in which to cause trouble. If we look at the who’s who of infectious diseases, we can see that the top ‘problems’ use social systems to help cause us suffering. Staphylococcus aureus better known as the SA in MRSA, the deadly hospital-acquired infection, is a proud member of the quorum sensing club.

In my lab, we focus on Pseudomonas aeruginosa; this bacterium has a nasty habit of infecting immunocompromised patients. It is of a particular worry to the cystic fibrosis population, as it is a leading cause of death in cystic fibrosis patients. The aim of this research is to understand how bacteria communicate, so that we can eavesdrop on this network and adjust how the bacteria behave. This goal becomes increasingly important each day as bacterial resistance to antibiotics becomes ever increasing.

Once again though, everything is not as it seems. It appears that some bacteria opt out of this social network in order to gain all the rewards of a social group with none of the costs. You can think of these bacteria as tax cheats. They provide nothing to the system but still take from it. This means, that compared to the socialites in their local environment, these cheats divert more energy into reproducing and begin to overrun the population, leading to the collapse of the society. It is just possible that we may be able to use these ‘cheats’ as a way of disrupting the day-to-day lives of infectious bacteria.

By sneaking in on our cheaters, we can alter the playing field which maintains virulence. We could also go one step further and use quorum sensing as a smart weapon against the very same bacteria. By modifying some genes and splicing in a few tricks, it should be possible to make an anti-bacterial ‘bomb’,  set to go off once the signal has reached significant levels.

Currently, we are looking at a very real and scary future in which antibiotics are no longer effective. We can buy ourselves time by clever prescription, but it’s still coming. Treating infection by manipulating communication might be a way in which we can move from the selection of resistant super bugs. However, we still need to realise that we cannot win this fight; we’re outnumbered and we’ve had it so good for a couple of generations. So perhaps it’s time we try to negotiate with the pathogens.

James Gurney


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