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.
Highlights
Studies in a number of bacterial pathogens in recent years have made it increasingly clear that the ability to assimilate nutrients in the course of host infection is crucial for pathogenesis [1,2,3,4,5]
Beyond the necessity to collect resources during infection, pathogens face a resource allocation dilemma: they have to use nutritional resources to proliferate inside the host, and in the other hand they need to mobilize matter and energy for the production of essential virulence factors
We provide evidence of that such a trade-off constrains antagonistically bacterial proliferation and virulence in the bacterial plant pathogen Ralstonia solanacearum
Summary
Studies in a number of bacterial pathogens in recent years have made it increasingly clear that the ability to assimilate nutrients in the course of host infection is crucial for pathogenesis [1,2,3,4,5]. The resource allocation trade-off is well documented in bacteria [18]: it has been shown for example to occur in the survival / multiplication balance under stress conditions [19] and there is evidence that bacterial growth strategies are the result of trade-offs in the economy of the cell [20,21]. This aspect has been poorly studied in the case of pathogens which have to simultaneously acquire nutrients, multiply and produce costly virulence factors in a stressful host environment. It is logical to presume that many pathogens experience a resource allocation trade-off to maintain both the proliferation (growth) and the virulence factor production traits during infection, the quantification of the cost for virulence is not documented
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
