Uropathogenic
Escherichia coli (UPEC), which
accounts for up to 90 % of all urinary tract infections (UTI), undergoes extensive
filamentation during the late stage of invasive infection of bladder cells. Filamentation
is caused by the arrest of bacterial cell division, with ongoing cell growth and
elongation. During UTI, filamentation is associated with bladder cell rupture, evasion
of phagocytosis, and re-binding to surfaces of the urinary tract. Bacterial
filaments can then recommence division to create rod-shaped cells and re-infect neighboring cells. The filamentation response is considered an important
bacterial survival strategy leading to ongoing infection and the transition to
dormancy and eventual acute UTI recurrence.
The
bacterial filamentation response and its reversal during infection are poorly
understood. Our research aims to understand the UPEC sensory/signalling pathway
and mechanism that leads to filamentation and reversal in UTI. We
have further developed the cell culture model of UTI, in which the infection of
human bladder cells can be measured by real-time microscopy in a flow-chamber
apparatus. Parameters such as bladder cell permeability are simultaneously
observed and related to the progress of the infection, in order to determine
the conditions that trigger bacteria filamentation; for example, we are fractionating
concentrated human urine and identifying the component(s) that trigger
bacterial filamentation. We will also discuss results from a novel
genome-wide screen that utilizes next-generation sequencing to identify UPEC
genes that promote bacterial filamentation and reversal.