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

AbstractEscherichia 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 anE. colistrain capable of efficiently proliferating without its cell wall. One of the mutations lead to enhanced expression ofrcsA, 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 howE. coliadapts to loss of its cell wall and that an increased synthesis of matrix constituents can compensate for the protective properties of the cell wall.SignificanceThe cell envelope is crucial for the protection ofE. coli. During bacterial infections such as urinary tract infections, antibiotics that disrupt cell wall synthesis are commonly prescribed. However, this can stimulate the formation of wall-deficient bacteria that are still able to proliferate despite the presence of these drugs. Our findings reveal that loss of the cell wall inE. coliincreases the production of extracellular matrix, a mechanism found in other unicellular organism too. This adaptation allows the bacteria to maintain their structural integrity and survive, highlighting a potential challenge in the successful treatment of bacterial infections.