Towards a Quantitative Modeling of the Synthesis of the Pectate Lyases, Essential Virulence Factors in Dickeya Dadantii

TL;DR

This paper presents a validated dynamic mathematical model of pectate lyase synthesis in Dickeya dadantii, integrating metabolic degradation and genetic regulation, revealing insights into bacterial virulence and potential bistability in gene expression.

Contribution

It introduces a novel integrated model combining metabolic and genetic regulation of pectate lyases, validated with experimental data, and predicts complex behaviors like bistability.

Findings

Pectin is almost fully consumed before Pel production peaks.

Model accurately predicts bacterial growth, Pel activity, and pectin consumption.

Suggests evolutionary strategy for bacteria to anticipate pectin availability.

Abstract

A dynamic mathematical model has been developed and validated to describe the synthesis of pectate lyases (Pels), the major virulence factors in Dickeya dadantii. This work focuses on the simultaneous modeling of the metabolic degradation of pectin by Pel enzymes and the genetic regulation of pel genes by 2-keto-3-deoxygluconate (KDG), a catabolite product of pectin which inactivates KdgR, one of the main repressors of pel genes. This modeling scheme takes into account the fact that the system is composed of two time-varying compartments: the extracellular medium, where Pel enzymes cleave pectin into oligomers, and the bacterial cytoplasm where, after internalization, oligomers are converted to KDG. Using the quasi-stationary state approximations, the model consists of some nonlinear differential equations for which most of the parameters could be estimated from the literature or from independent experiments. The few remaining unknown parameters were obtained by fitting the model equations against a set of Pel activity data. Model predictions were verified by measuring the time courses of bacterial growth, Pel production, pel mRNA accumulation and pectin consumption under various growth conditions. This work reveals that pectin is almost totally consumed before the burst of Pel production. This paradoxical behaviour can be interpreted as an evolutionary strategy to control the diffusion process so that as soon as a small amount of pectin is detected by the bacteria in its surroundings it anticipates more pectin to come. The model also predicts the possibility of bistable steady states in the presence of constant pectin compounds.