Making bacteria bilingual

SCTODAY

Like all bacteria, streptococci ‘talk’ to each other via pheromone and sensory receptor systems. Most speak only one ‘language’. What if it was possible to make them (at least) bilingual?

When bacteria are stressed, they can react in different ways. They can exchange genes by capturing fractions of external DNA and recombining them with their own genome to endure more effectively. They can also compete with and attack (predation) surrounding bacteria, including members of their own species.

‘We’re particularly interested in controlling predation,’ explains Prof. Pascal Hols, an FNRS research director at UCLouvain’s LIBST. ‘Indeed, we could program certain bacteria harmless to humans to attack pathogenic species. And manipulating their ComRS communication system might help us get there.’[1] 

How do bacteria talk to each other?

Because, yes, bacteria ‘talk to each other’! ‘They have communication systems that allow them to exchange information and coordinate a common response to a given stimulus,’ Prof. Hols says. ‘These systems are based on the production of pheromones and their detection by sensory receptors. The pheromone leaves the bacterium, accumulates in the environment, and is then picked up by the sensory receptor of the same species or another species bacterium.’ Pheromones are like radio messages sent and received by sensory receptors, which act like antennas.

Mono- and multilingual bacteria

In this regard, there are two cases:

  • The sensory receptor of this system is often strict. It recognises only one type of pheromone. The bacterium is then said to be monolingual and can’t communicate with bacteria that don’t speak its language.
  • The sensory receptor of some bacteria can be permissive. That is, it recognises two or more pheromones emitted by other bacteria. This bacterial ‘multilingualism’ is called ‘cross-talk’.
Teaching streptococci a new language

Whether for war, business, or diplomacy, mastering several languages is generally an asset! And what is valid for human beings is undoubtedly valid for bacteria. Prof. Hols’s team wanted to check whether it was possible to make a strict sensory receptor permissive. Or, in other words, to teach a bacterium a new language.

To do this, his team – particularly Laura Ledesma-García – joined forces with Prof. Sylvie Nessler’s team (University of Paris-Sarclay). Their first step was to study the sensory receptor’s structure. ‘The pheromone is housed in a pocket. By comparing the internal structure of the sensory receptor pockets of two different streptococci, we understood how the sensory receptor captures and interacts with the pheromone.

Modifying the sensory receptor pocket

The second step was to modify the pocket’s internal structure in order to force the sensory receptor to recognise other pheromones. Using site-directed mutagenesis techniques, the researchers generated a modified sensory receptor. ‘Hence we targeted a few amino acids in the pocket,’ Prof. Hols explains. ‘In doing so, we’ve broadened the spectrum of recognition for several pheromones. This allows the sensory receptor’s pocket to pick up and recognise not one but at least two different pheromones.’ So naturally monolingual streptococci become bilingual.

What’s the effect on bacterial predation?

The results of this experiment were the subject of an article[2] in the prestigious journal PNAS. ‘We’ve shown that it’s technically possible to modify the ComRS streptococcus communication system,’ Prof. Hols says. ‘Now we have to explore the tools we’ve generated. And see if our manipulations modify the behaviour of streptococci among themselves. Does this change anything in their predation? Do the bacteria that we’ve made bilingual have an advantage over others? If so, what is it? Ultimately, would there be a therapeutic interest in creating new pheromone-sensory receptor pairs?’ The future and further research will tell us.

Streptococci

Streptococci (Streptococcus) are gram-positive bacteria. This kind of bacteria includes a great number of species. They are often divided into two main categories:

  • Commensal species make up part of our intestinal, oral and other flora. Some are even probiotics, such as S. salivarius.
  • Pathogenic species are capable of causing infections in humans. Examples: S. pyogenes (bacterial tonsillitis, abscesses, etc.), S. mutans (tooth decay), and S. pneumoniae (which causes pneumonia and bacterial meningitis).

Candice Leblanc

A glance at Pascal Hols' bio

Pascal Hols is a professor and FNRS research director at UCLouvain. He is a member of UCLouvain’s LIBST Biochemistry and Genetics of Microorganisms Group (BGM). He holds a master’s degree in biology-biotechnology obtained in 1987 from the University of Namur, and a master’s degree in molecular biology and a PhD in science obtained in 1991 and 1994 respectively from UCLouvain. His research focuses mainly on the molecular biology of lactic acid bacteria.

 

 

 

A glance at Laura's bio Ledesma-García

Laura Ledesma-García has been a postdoc researcher at the UCLouvain BGM Laboratory since 2015. She holds a master’s degree and a PhD in biotechnology obtained respectively in 2007 and 2012 at the Universidad Pablo de Olavide Pablo de Sevilla (Spain).

 

 

 

 

[1]ComR and ComS are respectively the regulator and the pheromone which form the ComRS communication system.
[2]L. Ledesma-García et al., ‘Molecular dissection of pheromone selectivity in the competence signaling system ComRS of streptococci’, in PNAS, 20 March 2020.

Published on May 25, 2020