Quote: Santos-López A, Rodríguez-Beltrán J, San Millán Á (2021) The bacterial capsule is a gatekeeper for mobile DNA. PLoS Biol 19 (7): e3001308. https://doi.org/10.1371/journal.pbio.3001308

Released: July 6, 2021

Copyright ©: © 2021 Santos-López et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which allows unrestricted use, distribution, and reproduction in any medium, provided that the original author and source are acknowledged.

Financing: The author (s) did not receive any special funding for this work.

Competing interests: The authors have stated that there are no competing interests.

Bacteria have populated almost every corner of the earth for billions of years, showing an unprecedented ability to adapt to different environments and conditions. An important bacterial adaptation is the capsule, an outer layer of polysaccharides that covers the cells of many different types of bacteria. Capsules act as a kind of magical cloak, protecting bacteria from toxic compounds and dehydration, allowing them to adhere to surfaces and escape the host’s immune system. As a result, capsules are important virulence factors and some types of capsules are strongly associated with virulent strains of human pathogens [1] .

But how do bacteria acquire ecologically relevant properties like the capsule? Bacteria are known to be involved in horizontal gene transfer (HGT), a process by which bacteria acquire mobile genetic elements (MGEs) that carry specific traits that drive their evolution. MGEs are specialized vectors that can transfer DNA directly between different bacterial cells. Two of the most important MGE types are bacteriophages (phages), which are viruses that infect bacteria, and conjugative plasmids, which are small circular DNA molecules that travel from cell to cell through a plasmid-encoded channel Cell can jump. For example, conjugative plasmids are the primary vehicle for the dissemination of antibiotic resistance genes among bacterial pathogens, which is a major public health threat [2] .

As a thick outer layer, the bacterial capsule provides an inherent barrier to plasmid and phage transfer. In fact, the capsule is known to prevent phage infection in bacteria by hiding the surface receptors that phage use to invade [3] . But the interplay between capsule and phage is much more complex: phages are able to turn the tide by developing mechanisms to adhere to and invade certain types of capsules, resulting in strong capsule specificity in phage infections [4] .

Phages, plasmids and capsules are therefore key players in the evolutionary success of pathogens. How the interaction between the two different MGE types and the bacterial capsule affects HGT, however, has not been officially investigated until recently. In a new and elegant study by the Microbial Evolutionary Genomics group (Institut Pasteur, Paris), Haudiquet and colleagues combined sophisticated in silico and in vitro approaches to shed new light on this topic [5] . After a comprehensive analysis of approx. 4,000 genomes of the respective opportunistic pathogenKlebsiella pneumoniae, the authors proposed a simple and elegant model to explain the interaction between capsule, phage and plasmids (Fig. 1). First they showed that phages, as expected due to their high specificity, preferentially mediate the genetic exchange between bacteria of the same capsule type. Their results also showed that K. lung infectionClones often lose their capsule to avoid phage predation [4] . Next, the authors confirmed that unencapsulatedK. lung infectionIndeed, clones are more susceptible to conjugative plasmids than encapsulated ones, a finding that has been confirmed experimentally in representative strains of this species. Interestingly, in an earlier work by the same group, Rendueles and colleagues reported that capsule loci can be encoded in plasmids [6] . These results led the authors to hypothesize that the higher rate of plasmid conjugation in non-encapsulated cells might actually promote capsule reuptake, a hypothesis they supported by bioinformatic analysis. In summary, the authors described a subtle interaction between phages, plasmids andK. lung infectionresulting in capsule replacement through an intermediate and self-limiting non-encapsulated state.

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Fig. 1. The capsule trade encourages the acquisition of new mobile DNA.

The bacterial capsule influences the horizontal acquisition of new genetic elements in K. lung infection. (1) Phage are able to transfer DNA between bacteria belonging to the same capsule type (the capsule is indicated by a blue shade that surrounds the bacterium). Capsule inactivation (1 → 2) leads to resistance to phage infection, but increases the permissivity for plasmid uptake through conjugation. Conjugative plasmids can promote capsule reuptake (2 → 3) or direct exchange (1 → 3; dashed arrow), which can lead to a new capsule type (new capsule is indicated by green shading around the bacterium). Then new capsule-specific phages transfer DNA to the bacterium. The amount of new DNA transduced by the phage will decrease over time (1 and 4) as most of the DNA exchanges would take place between genetically similar organisms. The lower part of the figure is a conceptual representation of bacterial access to new horizontally acquired genes throughout the process. Plasmids are an important source of new genes, while phage-mediated access to new DNA is particularly important after changing capsule types will, when the bacterium has access to new phages, bring with them the more diverse DNA (from phylogenetically more distant bacteria). HGT, horizontal gene transfer.

https://doi.org/10.1371/journal.pbio.3001308.g001

A particularly interesting discovery of the study by Haudiquet and colleagues is the fact that trade in capsules – both capsule inactivation and / or capsule swap – increases with an increase in the acquisition of MGE (both plasmids and phages) in K. lung infectionLines. As explained earlier, the authors provide an excellent explanation for the mechanistic basis of this sudden increase in permissivity for mobile DNA, as well as for its self-limiting nature. It is tempting to speculate that this temporal increase in the flow of new MGE could represent an important opportunity for bacterial evolution (Fig. 1). Let’s elaborate on this idea; Phage easily transfer DNA between bacteria belonging to the same capsule type through generalized, specialized, and lateral transduction (the latter type is particularly important for chromosomal hypermobility). [7,8] ). Aside from the genes required for their life cycle, phages can encode a reduced number of accessory genes, which can benefit the recipient bacteria. In addition, phages “accidentally” transfer fragments of the bacterial chromosome at high frequency, which can be integrated into the chromosomal DNA of the recipient bacteria. However, given the high capsule specificity of phage, it is to be expected that phage-mediated access to new DNA will diminish over time as most of the DNA exchanges would take place between genetically similar individuals. In contrast, the capsule trade leads to a sudden increase in the availability of new MGE: conjugative plasmids that carry numerous and new genes and phages adapted to a different type of capsule that will bring a more diverse DNA. Therefore, the capsule trade can be strongly linked to the acquisition of new DNA due to this side effectK. lung infectionthat acts as an evolutionary catalyst in this particularly relevant opportunistic pathogen.

The study by Haudiquet and colleagues opens up new and exciting research paths. The most immediate questions concern the specifics of capsule inactivation / capsule replacement and its effects on HGT, e.g. B. how often and for how long K. lung infection Lines are not encapsulated? How much more revealing are they getting towards MGE? And how this freedom of movement works K. lung infectionEvolution? This study also suggests more general considerations. For example, it highlights the importance of considering the combined effects of different types of MGE when studying HGT. Most of the work on MGE has focused on the isolated effects of plasmids, phages, or other MGE. However, it is becoming increasingly clear that different types of MGE are working simultaneously and sometimes even in a coordinated manner [9–11] , and new studies will help better understand how MGE interactions affect bacterial evolution. Finally, this study also emphasizes the influence of the host range of different MGE on their potential impact on bacterial evolution. Phage represent a very limited host range, while plasmids and other conjugative elements, such as integrative and conjugative elements, can spread to more phylogenetically diverse hosts, from within a species to DNA transfer between kingdoms [12] . Future studies will be needed to uncover how this varying scale of host range can determine not only the ecology but also the genetic load of MGE.

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