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Abstract
Neutrophils are the most prominent cell of the human innate immune system. Upon infection by bacteria, neutrophils are recruited to the site of infection where they target bacteria for degradation by phagocytosis. Neutrophils are effective bacterial killers through a high production of reactive oxygen species (ROS) and reactive chlorine species (RCS), which kill ingested microbes through damage to nucleic acids, lipids, and proteins. To prevent succumbing to the lethal effects of oxidative stress, pathogens such as Uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections (UTIs), have developed defense systems to combat ROS/RCS. We recently identified the most prominent HOCl defense system in UPEC to be RcrB, an outer membrane protein whose function remains enigmatic. Expression of RcrB is regulated by the HOCl-sensing transcriptional repressor RcrR. However, within the neutrophil, HOCl is highly reactive with primary and secondary amines, forming chloramines. Here, we show that expression of RcrB can be induced by several ROS/RCS and that RcrB provides protection from multiple RCS, such as Gly-Cl and NCT. Further, we show that the kinetics of RcrB expression differ from other HOCl defense systems RclC and NemA, with RcrB playing the most important role in protecting UPEC from HOCl stress.
