Metal-Organic Framework Enhanced Cellular and Humoral Immune Response Against Sepsis Causing Infection

Abstract

Urinary tract infection (UTI) is the most common adult bacterial infections worldwide, with ~80% of all uncomplicated UTI caused by uropathogenic E. coli (UPEC). While anyone can develop a UTI, women in their 20’s and postmenopausal women are at particularly high risk—indeed, half of all women will develop a UTI in their lifetime. Even with antibiotic therapy, 25-50% of patients will experience recurrence within a year.1 Initial and subsequent UTIs can alter bladder epithelial cell barrier function, which in turn creates an environment more favorable to subsequent infection.2 This results in recurrent UTI, which requires long-term antimicrobial therapy and can reoccur in a patient indefinitely, causing a lifetime of pain, discomfort, and an elevated risk of septicemic death.3 Unfortunately, antibiotic resistance makes treating UTIs less effective. Indeed, 10–25% of uncomplicated UTI patient isolates are resistant to trimethoprim/sulfamethoxazole (TMP/SMX)—the standard-of-care antibiotic regime for UTI.4 , 5 Alarmingly, >70% of postmenopausal recurrent UTI patients are either allergic or resistant to TMP-SMX.5 Given the ubiquity of these infections and the high likelihood of recurrence, the societal cost is estimated to be over $5 billion each year in the US alone.6 A prophylactic or therapeutic vaccine would be an ideal first line of defense against UTIs for high risk groups, but no FDA-approved vaccines against UTI—or indeed any pathogenic E. coli infection—exist.7