A Resource Allocation Trade-Off between Virulence and Proliferation Drives Metabolic Versatility in the Plant Pathogen Ralstonia solanacearum

PLoS Pathog. 2016 Oct 12;12(10):e1005939. doi: 10.1371/journal.ppat.1005939. eCollection 2016 Oct.

Abstract

Bacterial pathogenicity relies on a proficient metabolism and there is increasing evidence that metabolic adaptation to exploit host resources is a key property of infectious organisms. In many cases, colonization by the pathogen also implies an intensive multiplication and the necessity to produce a large array of virulence factors, which may represent a significant cost for the pathogen. We describe here the existence of a resource allocation trade-off mechanism in the plant pathogen R. solanacearum. We generated a genome-scale reconstruction of the metabolic network of R. solanacearum, together with a macromolecule network module accounting for the production and secretion of hundreds of virulence determinants. By using a combination of constraint-based modeling and metabolic flux analyses, we quantified the metabolic cost for production of exopolysaccharides, which are critical for disease symptom production, and other virulence factors. We demonstrated that this trade-off between virulence factor production and bacterial proliferation is controlled by the quorum-sensing-dependent regulatory protein PhcA. A phcA mutant is avirulent but has a better growth rate than the wild-type strain. Moreover, a phcA mutant has an expanded metabolic versatility, being able to metabolize 17 substrates more than the wild-type. Model predictions indicate that metabolic pathways are optimally oriented towards proliferation in a phcA mutant and we show that this enhanced metabolic versatility in phcA mutants is to a large extent a consequence of not paying the cost for virulence. This analysis allowed identifying candidate metabolic substrates having a substantial impact on bacterial growth during infection. Interestingly, the substrates supporting well both production of virulence factors and growth are those found in higher amount within the plant host. These findings also provide an explanatory basis to the well-known emergence of avirulent variants in R. solanacearum populations in planta or in stressful environments.

MeSH terms

  • Cell Proliferation / physiology
  • Gram-Negative Bacterial Infections / metabolism
  • Metabolic Networks and Pathways
  • Nuclear Magnetic Resonance, Biomolecular
  • Plant Diseases / microbiology*
  • Ralstonia solanacearum / metabolism*
  • Ralstonia solanacearum / pathogenicity*
  • Virulence / physiology*
  • Virulence Factors / metabolism

Substances

  • Virulence Factors

Grants and funding

RP was supported by EMBO (Long-Term Fellowship ALTF 1627-2011), Marie Curie Actions (EMBOCOFUND2010, GA-2010-267146), and European Research Council (ERC-StG336808 project VariWhim). We acknowledge funding from the Institut National de la Recherche Agronomique (Plant Health Division grant AAP SPE 2012) and the French Laboratory of Excellence project TULIP (ANR-10-LABX-41; ANR-11-IDEX-0002-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.