Pathogens and their hosts have evolved complex and competing strategies to gain an advantage in the game of survival. In the most basic relationship, invading pathogens are recognized by the host’s immune system which responds by killing them. Specialized cells, known as phagocytes, hunt and engulf the pathogens. Within the phagocyte, the pathogen is then shuttled for destruction by the lysosome, an organelle that contains numerous bactericidal agents including degradative enzymes whose actions are enhanced by the lysosome’s acidic pH.
In response, pathogens have developed tactics to evade degradation by immune cells. Some pathogens are even able to trick non-immune cells into internalizing them, effectively hiding from impending doom. Such is the case with uropathogenic Escherichia coli (UPEC), a major causative agent of uncomplicated urinary tract infections. UPEC causes infections by invading bladder epithelial cells (BECs), the bladder’s barrier to urine. UPEC exploits the BECs’ ability to expand its cell surface when accommodating large volumes of urine. When the BECs reverse this expansion by retracting its cell surface, UPEC tags along and slips into the cell unannounced. Interestingly, BECs are able to deal with this trickery by expelling most of the UPEC out of the cell. How BECs are able to do this has remained a mystery until now.
A study done by the Abraham group has shown how the internalization of UPEC into BECs leads to an intricate chess match. When the BECs realize they have been infected, the BECs attempt to degrade UPEC by autophagy, a process that allows the cell to recycle excess or damaged macromolecules and organelles. This cargo is packaged into new organelles called autophagosomes that are then broken down by the lysosome. In this way, UPEC are packaged into autophagosomes and fated for destruction by the lysosome. But UPEC has other plans; they can evade degradation by neutralizing the lysosome’s high acidity, thereby impairing the action of many of its bacteria-killing enzymes. Not to be outdone, the host has many proteins on the lysosome that can sense abnormalities, including the loss of acidity. One such protein identified by the Abraham group is the calcium channel mucolipin TRP channel 3 (TRPML3) which monitors the acidity of the lysosome. When TRPML3 senses that the lysosome is no longer acidic, it releases the calcium stored within the lysosome. Upon release, calcium ions promote the fusion of the lysosome with the cell surface, resulting in the expulsion of the lysosomal content, including the intact UPEC, out of the cell and into urine.
Cells display an intricate ability to monitor and maintain its normal function with the goal of minimizing the impact of irregularities such as an infection. The ability for BECs to deal with UPEC is an example of a cellular self-defence mechanism that takes advantage of many of the cells existing machinery and processes to effectively return to homeostasis. However, UPEC infections still account for a large number of urinary tract infections despite the host cell’s ability to defend itself, which suggests that UPEC has other tricks up its sleeve. The fight for survival will continue to develop interesting mechanisms for both pathogens and hosts throughout the course of evolution. At the end of the day, both pathogens and hosts are just struggling for survival in this big, little world that we all share.
Miao, Y., Li, G., Zhang, X., Xu, H., & Abraham, S. N. (2015). A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. Cell, 161(6), 1306-1319.