MicrobiologyBytes

Gathering and sharing of information is extremely important in human society. Especially in times of war, the difference between victory and defeat can depend on the ability to obtain, encrypt, and share information, and sophisticated systems have been developed for exactly this purpose. Similarly, in their constant battles with competitors and the host immune system, (opportunistic) microbial pathogens have developed sophisticated cell–cell communication systems termed quorum sensing (QS) that allow exchange of critical information. In return, competing microbes, as well as the host immune system, have developed means to intercept and decode these messages. The information obtained by this molecular espionage is used for their benefit, either to win the war (microbe against microbe), or to prepare for an upcoming battle (microbe against immune system).

QS is a system that enables microbes to monitor population cell density through the production, secretion, and sensing of small diffusible molecules. When such molecules reach a threshold concentration, microbial cells in the vicinity detect the signal and coordinately respond by modifying their gene expression; often these genes are associated with virulence and pathogenesis. Several different types of QS molecules have been described for a wide variety of microbial species.

To illustrate the clinical importance of this microbial spy game, this short review focuses on the biological activity of a single bacterial QS molecule on surrounding microbes and the host immune system and its diverse “meaning” to different receivers. Infections related to burn wounds, cystic fibrosis, and periodontal diseases consist most commonly of the bacteria Pseudomonas aeruginosa and Staphylococcus aureus and the fungus Candida albicans, and represent niches with an active host response. This short review provides five facts about how the P. aeruginosa QS molecule plays a pivotal role in this triangle of interspecies interactions and how microbial behavior elicited by this small signalling molecule has consequences for the host response.

Microbial Spy Games and Host Response: Roles of a Pseudomonas aeruginosa Small Molecule in Communication with Other Species. (2011) PLoS Pathog 7(11): e1002312. doi:10.1371/journal.ppat.1002312

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Bacterial communities often synthesize and embed themselves in a sticky polymer matrix known as a biofilm which provides a safe environment protected from many environmental stresses. As Steve Atkinson describes in this article in Microbiology Today, for this mode of living to be successful the members of the community need to communicate:

When the first bacteria were observed with a microscope, it must have been something of a leap of faith to believe they were living organisms, let alone consider that they were not behaving as individuals, but were in fact co-operating in a coordinated community where cell-to-cell communication plays an integral part in their life cycle. As early as 1905, Erwin Frink Smith, in his manuscript Bacteria in relation to plant disease was astute enough to comment that ‘a multiple of bacteria are stronger than a few’, but it was not until the early 1990s that the concept of bacterial cell-to-cell communication actually gained credence within the microbiological community with the discovery that bacteria employ chemical signals (pheromones) to communicate, and so coordinate population-wide behaviour with changes in environmental conditions. The concept of bacterial cell-to-cell signalling, usually referred to as quorum sensing (QS), has now been observed in a wide variety of Gram-positive and Gram-negative plant and animal pathogens, including those responsible for important human diseases. It is also noteworthy that QS systems are not limited to prokaryotes, but have also been described in eukaryotes such as yeast.

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Traditional treatment of bacterial infections relies heavily on the use of antibacterial compounds that either kill bacteria (bactericidal) or inhibit their growth (bacteriostatic). Typically, the targets for the main conventional antibiotics are essential cellular processes such as bacterial cell wall biosynthesis, bacterial protein synthesis, and bacterial DNA replication and repair. However, resistance to these drugs arises and spreads very rapidly, even to such an extent that bacteria have been identified that are simultaneously resistant to all available antibiotics. The increasing occurrence of resistant bacteria gradually renders antibiotics ineffective in treating infections and has enormous human and economic consequences worldwide. As a result, the identification of novel drug targets and the development of novel therapeutics constitute an important area of current scientific research. An alternative to killing or inhibiting growth of pathogenic bacteria is the specific attenuation of bacterial virulence, which can be attained by targeting key regulatory systems that mediate the expression of virulence factors. One of the target regulatory systems is quorum sensing (QS), or bacterial cell-to-cell communication. QS is a mechanism of gene regulation in which bacteria coordinate the expression of certain genes in response to the presence or absence of small signal molecules. As the importance of QS in virulence development of pathogenic bacteria became clear, about a decade ago, QS disruption was suggested as a new anti-infective strategy.

Although at this moment it is difficult to accurately estimate the risk of resistance development, this paper argues that scientists need to pay attention to the possibility that it will evolve. Once we have better knowledge of the risk of resistance development to QS disruption, it might be possible to direct further research on QS inhibition preferentially towards strategies that include a lower risk of resistance development.

Can Bacteria Evolve Resistance to Quorum Sensing Disruption? 2010 PLoS Pathog 6(7): e1000989. doi:10.1371/journal.ppat.1000989

Our view of bacteria, from the earliest observations through the heyday of antibiotic discovery, has shifted dramatically. We recognize communities of bacteria as integral and functionally important components of diverse habitats, ranging from soil collectives to the human microbiome. To function as productive communities, bacteria coordinate metabolic functions, often requiring shifts in growth and development. The hallmark of cellular development, which we characterize as physiological change in response to environmental stimuli, is a defining feature of many bacterial interspecies interactions. Bacterial communities rely on chemical exchanges to provide the cues for developmental change. Traditional methods in microbiology focus on isolation and characterization of bacteria in monoculture, separating the organisms from the surroundings in which interspecies chemical communication has relevance. Developing multispecies experimental systems that incorporate knowledge of bacterial physiology and metabolism with insights from biodiversity and metagenomics shows great promise for understanding interspecies chemical communication in the microbial world.

Interspecies chemical communication in bacterial development. Ann Rev Microbiol. 2009 63: 99-118

Related:

• Communication, cooperation, competition and cheating – bacteria are just like us
• Quorum Sensing in Bacteria: We Two Are One
• Bacterial Crowd Control
• Pneumococcus: the quorum-sensing killer
• Quorum sensing in Serratia

A recent article in New Scientist entitled Why microbes are smarter than you thought looks at six behaviours that seem remarkably intelligent for single celled organisms. Single-celled organisms don’t have nervous systems, let alone brains, but they could be viewed as “biological computers” with internal machinery that can process and respond to information.

On MicrobiologyBytes I’ve often discussed bacterial communication – the ways in which bacteria talk to each other using chemical signals. If Bacillus subtilis cells are growing in a nutrient-poor area, they release chemicals into their surroundings which tell their neighbours “There’s not much food here, so clear off or we’ll both starve.” In response to these chemical messages, the other bacteria move away, changing the shape of the colony.

Many single-celled organisms can work out how many other bacteria of their own species are in their vicinity – something known as “quorum sensing“. Each individual bacterium releases a small amount of a chemical into the surrounding medium. If there are lots of other bacteria around, all releasing the same chemical, levels can reach a critical point and trigger a change in behaviour of the whole population. This “voting system” can be used to decide when to launch an attack on a host. Once they have grown to sufficient numbers to overwhelm the immune system, they collectively launch an assault on the body. Jamming these signals might provide us with a way to fight back.

Bacteria form communities known as biofilms, familiar as the thin layer of slime that coats the insides of water pipes, or surgical implants. Many different species live side by side in these “bacterial cities”, consuming each other’s wastes, cooperating to exploit food sources, and safeguarding one another from external threats such as antibiotics.

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Many microbes can accelerate the rate at which their genes mutate. This allows them to obtain new abilities that may be helpful when conditions get tough. Escherichia coli mutates more rapidly when under stress (Stress-induced mutagenesis in bacteria. Science. 2003 300(5624): 1404-9), and yeast can perform the same trick (Adaptive mutation in Saccharomyces cerevisiae. Crit Rev Biochem Mol Biol. 2007 42(4): 285-31).

Microbes are also pretty good at navigation. The single-celled algae Chlamydomonas swim towards light, but only if it is of a wavelength that they can use for photosynthesis. Some bacteria move according to the presence of chemicals in their environment – a behaviour called chemotaxis. Another group of bacteria align themselves to the Earth’s magnetic field, allowing them to head directly north or south, and more importantly, up or down for optimum photosynthesis.

When the amoeba Dictyostelium searches the surface of a Petri dish for food, it makes frequent turns. But it does not do so randomly. If it has just turned right, it is twice as likely to turn left as right on its next turn, and vice versa. It remembers which direction it last turned.

Remarkable though these behaviours are, we have probably only scratched the surface of what single-celled organisms can do. With so many still entirely unknown to science, there must be plenty more surprises in store.

Related:

• Quorum Sensing
• Biofilms
• It’s good to talk
• Communication, cooperation, competition and cheating – bacteria are just like us

Bacteria “talk” to each other using a chemical language (“quorum sensing”) that lets them coordinate defense and mount attacks. The find has stunning implications for medicine, industry and our understanding of ourselves.

Related:

• Quorum Sensing in Bacteria: We Two Are One
• It’s good to talk
• Pneumococcus: the quorum-sensing killer
• Quorum sensing in Serratia
• Quorum sensing is a master regulator of phytopathogenesis