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6.3 Evolution in biofilms - Part 2, by Associate professor Steve Diggle

Course video 27 of 28

Dear all, welcome to this last module of the course. In this module you will learn about the evolutionary aspects of biofilms. You will hear about how bacteria adapt to chronic infections and how bacteria can cooperate or fight each other. I hope you will have fun CheersThomas

This course will give you an introduction to bacteria and chronic infections. Leading experts in the field will make you familiar with the fundamental concepts of microbiology and bacteriology such as single cell bacteria, biofilm formation, and acute and chronic infections.

Destrezas que aprenderás

Antimicrobial, Infection Control, Microbiology, Bacteriology

Impartido por:

Thomas Bjarnsholt
Professor

Transcripción

Hello everyone, my name is Steve Diggle and I am an Associate Professor in Sociomicrobiology

in the School of Life Science at the University of Nottingham in the UK. I started my research

career looking at the molecular mechanisms that control cell-to-cell signalling, usually

known as quorum sensing, in the opportunistic pathogen Pseudomonas aeruginosa. In 2006 I

was awarded a fellowship from the Royal Society to study quorum sensing from a more evolutionary

perspective. So, rather than working on ‘how’ quorum sensing works, I started to ask ‘why’

questions such as ‘is quorum sensing really a social behaviour’ and ‘why is it maintained

in natural populations’. Such questions are asked in the field of social evolution

and so in this lecture, I will tell you about social evolution in microbes, and at the end,

discuss why this is important in biofilms. In a microbial biofilm, innumerable cells

form complex structures in which each individual cell plays only a small role. Much of the

literature traditionally describes a biofilm as a coordinated and cooperative unit where

the activity of each individual cell benefits the overall group. Upon closer inspection

however, this is not always the case. First, the architectural features such as mushroom

like structures, water channels and stratifications may be the result of chemical gradients, simple

growth parameters and physiological adaptation to a particular micro-niche. These can arise

with no coordination, cooperation or communication between participant cells. Second, when a

behaviour is performed that confers a cost to the individual performing the behaviour,

and a benefit to the surrounding population, that behaviour is vulnerable to cheating strategies

which do not contribute a benefit to the population but benefit individuals. In this lecture I

will describe social evolution and social behaviours in microbes and discuss why this

might be important in biofilms. Before we talk specifically about biofilms,

let us first discuss why we might be interested in studying social evolution in microbes.

Social evolution has become an active area of research in microbiology for a number of

reasons. For example, microbes display many apparently social or cooperative behaviors,

and many of these behaviors seem to be crucial for those microbes to survive in their ecological

niches or to become successful pathogens. Biofılm formation could be a prime example

of a cooperative social behaviour. In addition, social evolution research also complements

mechanistic studies by presenting evolutionary problems for which there must be mechanistic

solutions. Next we must talk about what defines a social

behavior. There is a huge body of work examining microbial behaviours from a molecular perspective,

but comparatively little from an evolutionary standpoint. Social behaviours in microbes

have, until relatively recently, been ignored by evolutionary biologists, yet there has

been much work done in this area both theoretically and empirically in higher organisms such as

insects, birds and mammals. Social behaviours are those which have fitness consequences

for both the actor performing the behaviour and the recipient of the behaviour, and can

be broadly categorized into four types depending on the fitness consequences for both the actor

and the recipient. A behaviour that increases the fitness of the actor is mutually beneficial

if the recipient also benefits, and selfish if the recipient suffers a loss. A behaviour

that reduces the fitness of the actor is altruistic if the recipient benefits, and spiteful if

the recipient suffers a loss. It is important to understand the nature of the interaction

between actor and recipient as then we can make very different predictions as to how

such a behaviour evolves and is maintained in populations. One of the big challenges

for us as microbiologists, is to understand the multitude of behaviours that have been

described in a wide range of bacterial species from an evolutionary perspective, which will

increase our understanding of the nature of these behaviours, and complement previous

and future molecular work. Furthermore, understanding whether a behavior is social can help us understand

how bacterial populations interact within infected hosts, which will help explain how

virulence and antimicrobial resistance evolves. We could even use some of the ideas of social

evolution to help us reduce virulence during infection, and favourably improve the outcome

for patients. What are microbial social behaviours?

Microbial behaviours might seem simpler than those that have been described in higher organisms,

but they share a fundamental similar property: a shared investment in producing a group resource.

Many microbial social behaviours come in the form of public goods which are released into

the surrounding environment and are costly for individuals to make but provide a benefit

for all other individuals in the population. Microbes make a wide variety of public goods

including siderophores for iron scavenging, β-lactamases to inactivate antibiotics, exopolysaccarhides,

toxins, extracellular proteases, and quorum sensing signal molecules. I am sure that you

will be able to think of lots of other examples. However, despite the multitude of cooperative

behaviours seen in the natural world, explaining cooperative behaviours such as altruism has

been a significant challenge for evolutionary biologists. The problem arises because altruistic

behaviours, reduce the fitness of the actor. The question then becomes why help others

at a cost to yourself? This appears to conflict with Charles Darwin’s idea of the survival

of the fittest, because natural selection favours those individuals with the greatest

reproductive success relative to the rest of the population. It is therefore difficult

to see why altruistic behaviours, which reduce the fitness of the actor, can be evolutionarily

favoured. Because an actor accrues a fitness cost by performing a behaviour, there is the

potential of exploitation by cheats or freeloaders who do not cooperate, and who therefore gain

a fitness advantage in the population because they do not pay the costs of cooperation.

This is sometimes referred to as a ‘tragedy of the commons’, which was originally used

to describe human economics and morality, but can also be applied to microbes. The tragedy

is that if everyone cooperated this would benefit the population, but cheating, even

though these individuals benefit in the short term, puts the entire population at a risk

of collapse or extinction. To illustrate social evolution in microbes

we will look at the well studied social trait of quorum sensing. This is a process where

cells communicate with each other via diffusible signal molecules. These signals coordinate

a wide range of behaviors at the population or group level. In a range of gram-negative

and gram-positive bacterial species, QS signals regulate the production of extracellular “public

goods,” including nutrient-scavenging molecules, exoproteases, toxins, and surfactants that

aid cellular motility. In the opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus

aureus, quorum sensing has been shown to be both costly and exploitable by cheats. Using

a synthetic growth medium where quorum sensing-dependent exoprotease production is important for growth,

wild-type Pseudomonas aeruginosa populations grow well, but populations of quorum sensing

mutants grow poorly. Crucially, in mixed cultures, quorum sensing mutants act as social cheats

because they have a fitness advantage due to exploitation of the exoprotease production

of wild-type cells. Similarly, when mice with burned skin or with chronic wounds are infected

with Pseudomonas aeruginosa, quorum sensing mutants act as cheats and invade the bacterial

population within days. In waxmoth larvae infections, a similar pattern of sociality

for Staphylococcus aureus can be observed. Quorum sensing mutants are less fit than their

wild-type counterparts in monoculture infections but demonstrate social cheating when in mixed

infection. Such results help us to explain why quorum sensing mutants often arise in

clinical infections even though such loss-of-function mutations might appear to be detrimental to

fitness. Furthermore, mixed infections of wild type cells with cheats, show a reduced

virulence, because cheats do not make tissue damaging toxins. This could be used to our

advantage because cheats could be introduced into infections to both reduce virulence and

buy time for the immune system to deal with the infection. This has resulted in the term

‘cheatobiotics’, but a lot more research is need in this area.

How can cooperation be maintained in the light of cheating?

A key question in the social evolution field is how are social behaviours maintained given

that cheats enjoy large fitness advantages in mixed populations? One of the most studied

ideas is ‘inclusive fitness’. This is the idea that an individual maximises its

inclusive fitness, not just by maximising its own reproduction, but the reproduction

of its genes even if they happen to be in other individuals. So by helping a relative

reproduce, this still increases inclusive fitness. This theory was developed by the

evolutionary biologist William Hamilton in the 1960s, and has since been termed ‘kin

selection’. A classic example of this can be found in insects. Many social insects such

as bees and ants, have sterile worker castes that completely forgo their own reproduction

in favour of that of the queen. How is this altruism inherited if the altruists never

reproduce? The behaviour can be inherited if the benefits accrue to individuals which

share the genes for altruism. This is the case in insects, but how does this manifest

in bacterial populations? Selection for cooperative traits in microbes can be maximized when relatedness

is kept high but how can this be achieved? One way that kin selection can work is via

limited dispersal. Here relatives are kept close together, increasing the probability

of interactions occurring amongst relatives, which favours indiscriminate altruism towards

neighbours. This does not require complex recognition systems, and therefore is likely

to be important in microbes. Biofilms and cooperation

Many of the experimental social evolution studies so far, have been performed in well

mixed planktonic cultures, where there is ample opportunity for cheats to freely disperse

and indiscriminantly exploit public goods production by cooperators. One key way for

microbes to limited dispersal, is to grow in a biofilm which is surrounded by an exopolysaccarhide

matrix. Such a spatially structured environment has the potential to keep cooperating genotypes

together and limit the invasion and spread of cheating genotypes. A possible outcome

of this is the general maintenance of social traits within the biofilm. Though it might

seem obvious that the formation of a biofilm involves cooperation between cells, the processes

involved need not always be cooperative. Inspired by spectacular modern microscopic observations

of biofilms, such as the mushroom-like structures of Pseudomonas aeruginosa, researchers have

modeled in silico, the growth and spatial patterns of cells growing on a surface with

interesting results. Using these computer simulations, it is possible to observe the

types of vertical structures typical of in vitro biofilms using only basic growth limitation

criteria in the environment and simple growth parameters of the organism. Secondly, in competitive

growth simulations between a wild type bacterium and a mutant that does not produce a ‘scaffolding’

polymer, a polymer mutant can be outgrown and covered by the cooperative wild type.

Where oxygen gradients are present, an overproducer of the scaffold polymer pushes its cell lineage

vertically into favourable oxygen conditions. In this in silico model of growth on a surface,

mixing genotypes does not select for cheating due to the local benefit of polymer secretion.

However if you introduce a new parameter to the model, the possibility that one genotype

can mutate into the other, the result is different. The cheating mutant now gains an advantage

if it occurs in an oxygen rich region where it can quickly produce lots of cells. The

key point here is that both the biological environment, and the social environment, determine

where and how we expect to observe biofilm formation, and why biofilms are maintained.

We are only just beginning to study social behaviours in biofilms, and it is now crucial

that we perform experimental tests to confirm the predictions that are observed during computer

simulations. This will help to inform us why biofilms form, and which traits are social

and non-social in biofilms. This is important because it will allow us to test whether targeting

specific traits, will result in us being able to better control biofilms, which are becoming

increasingly problematic in clinical and industrial settings.

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