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GOOD OR BAD BUGS, FRIEND OR FOES: UNRAVELING DIFFERENCES BETWEEN MUTUALISM AND PATHOGENICITY IN BURKHOLDERIA SPECIES

Periodic Reporting for period 1 - GOOD OR BAD BUGS (GOOD OR BAD BUGS, FRIEND OR FOES: UNRAVELING DIFFERENCES BETWEEN MUTUALISM AND PATHOGENICITY IN BURKHOLDERIA SPECIES)

Reporting period: 2021-09-01 to 2023-08-31

Microbiologists John Govan and Peter Vandamme once said something that caught my attention: “What better microbial challenge to unite agricultural and medical microbiologists than a microorganism that reduces an onion to a macerated pulp, protects crops from diseases, devastates the health and social life of cystic fibrosis patients, and not only is resistant to the most famous antibiotic, penicillin, but can use it as a nutrient!". They were speaking about bacteria from the genus Burkholderia!

This genus accommodates around one hundred and twenty species that colonize a wide range of ecological niches and interact with different hosts. For instance, B. cenocepacia is an opportunistic pathogen that produces severe infections in cystic fibrosis and immunocompromised patients, and which is usually resistant to many antibiotic treatments. Other species are environmental/soil commensals/saprophytes that are rarely pathogenic (B. thailandensis). Finally, some species such as B. phytofirmans and B. caledonica are mutualists that are beneficial to plants and could be potentially exploited in biotechnological processes, although the agricultural use of these beneficial species as plant growth promoting bacteria (PGPB) is severely being restrained due to the potential threat that a few opportunistic pathogenic strains pose to human health.

In the last years, a lot of effort has been invested into discriminating between the beneficial environmental (the “good”) and the clinical (the “bad”) Burkholderia strains, and several approaches have been used with this aim. For instance, phylogenetic and taxonomic analyses have given evidence that members of the genus Burkholderia can be separated into several lineages which agree more or less with their different lifestyles. One clade comprises animal and plant pathogens; and other, recently proposed as the novel genus Paraburkholderia, comprises environmental and plant-beneficial PGPB Burkholderia spp.

Good or bad bugs? Friends or foes? The global aim of this project is to unravel the differences between mutualism and pathogenicity in Burkholderia and Paraburkholderia. The goal is to study different ecological states of a group of species and to unravel the mechanisms that lead to mutualism or pathogenicity in different hosts. We hypothesize that the dissimilarities in the genomes of the Burkholderia and Paraburkholderia species allow them to interact with different types of hosts, leading to mutualism, opportunism, and/or pathogenicity.

The importance of achieving the ability to discern between the two of them and understand their colonization fitness genes concerns mainly two fields: public health/medicine and agriculture. Identifying the genes involved in animal and plant colonization will facilitate 1) the development of disease tools against pathogenic Burkholderia, and 2) the identification of targets to increase plant colonization by the beneficial Paraburkholderia.
We have used a genome-wide fitness assignation method, called transposon sequencing (TnSeq) to identify genes that are important or detrimental for a given condition, for instance colonization of animal and plant hosts. This gives us information on what genes within a genome can be targeted to give a lower or higher colonization ability to a bacterial strain.

During this project we have managed to identify a set of genes that could be targeted to decrease colonization by the pathogenic Burkholderia species, both in animal hosts and plant hosts. We have also unravelled a set of genes that can be targeted in the beneficial Paraburkholderia to increase plant colonization.
We are currently doing proof of concept experiments to validate the results obtained in differentially important genes for host colonization and be able to publish our results.

The outcome of this study is crutial information that will be of interest mainly at the agriculture/environmental sector, but also at the clinical/medicine levels. The knowledge produced could be exploitable crop companies and the pharmaceutical sector in order to develop new treatments to inhibit colonization by pathogenic Burkholderia, or to increase the colonization abilities of beneficial Paraburkholderia.

The ongoing global population is expected to continue growing for several decades. This requires that agriculture renews itself to become sustainable, for instance with the use of PGPB. Paraburkholderia are well-known PGPB, some of which have been commercialized and successfully used during many years, but then withdrawn from the market as a precautionary measure because a few strains are related to pathogenic species. Something similiar happens with other PGPB, such as Bacillus or Pseudomonas. Efforts are urgently needed to distinguish and manipulate both the pathogenic and the beneficial species.
Maize plants
Observation of a Paraburkholderia phytofirmans fluorescent-tagged strain colonizing plant roots