Enhanced extracellular matrix production provides protection to cell wall-deficientEscherichia coli

Abstract

Escherichia coli-induced recurrent urinary tract infections (rUTIs) present a complicated challenge within the medical field. Most first-line antibiotic treatments primarily target cell-wall synthesis, which can lead to the formation of cell wall-deficient cells. To investigate how such cells can sustain, we obtained an E. coli strain capable of efficiently proliferating without its cell wall. One of the mutations lead to enhanced expression of rcsA, encoding an important regulator involved in responding to cell envelope stress. RNA sequencing demonstrated an upregulation of genes associated with the production of extracellular matrix components, and this increased extracellular matrix production was confirmed using various imaging techniques. Remarkably, a subsequent long-term evolution experiment on this strain revealed a further augmentation in extracellular matrix production, coinciding with an enhanced ability to withstand harsh conditions. These findings demonstrate how E. coli adapts to loss of its cell wall and that an increased synthesis of matrix constituents can compensate for the protective properties of the cell wall.