How a Specific Component of Host Innate Immunity Modulates Microbial Evolution Towards Pathogenicity?

Researchers can use bacteria in controlled experimental environments to study evolution in real time. In-fact many bacteria have knack to adapt to abiotic challenges under lab environments, however less is known about affect of biotic challenges on adaptive evolution in bacteria.

Escherichia coli are versatile pathogens and commensals. Since there is evidence in literature that some E. coli that are pathogenic evolved actually from commensal strains, hence this organism becomes ideal for studying commensal to pathogenic switch. Most of laymen consider E. coli as friendly commensal, however when gastrointestinal barrier is disrupted, this commensal turns into pathogenic form. The break away from primary immune barrier or innate system is a critical trait relevant in the acquirement of bacterial virulence.

Since macrophages are defensive in nature, they directly attack pathogenic bacteria and kill them by RNS or ROS and phagocytosis. However, many pathogens have evolved mechanisms to evade such capture processes of macrophages. Such mechanisms include adaptive processes like capsule and biofilm formation.

In this study, researchers allowed E. coli to evolve under selective pressure of macrophages and tried to analyze how quickly and by which mechanism commensal E. coli develops resistance to macrophages. Several combinations of investigational evolution, phenotypic characterization, genome sequencing and mathematical modeling were used to tackle how fast and through how many adaptive steps commensal E. coli can acquire this immune evading virulence trait.

Results from the study indicate that E. coli can evolve and adapt very fast to evade innate immune system. Such pathoadaptive process involves the accumulation of mutations caused by transposon insertions and increasing pathogenicity in vivo. Under selective pressure E. coli can evolve in less than 500 generations using mechanisms;

  1.  Single transposable element insertion into the E. coli yrfF gene promoter.
  2. Insertion of IS186 into an ATP-dependent serine protease encoding Lon gene promoter.

Moreover authors have obtained a mathematical model that illustrates the dynamics of pathoadaptive process where in clones carrying distinct beneficial mutations emerge rapidly and turn virulent.

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Reference: The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages.

Migla Miskinyte, Ana Sousa, Ricardo S. Ramiro, Jorge A. Moura de Sousa, Jerzy Kotlinowski, Iris Caramalho, Sara Magalhães, Miguel P. Soares, Isabel Gordo. DOI: 10.1371/journal.ppat.1003802.


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