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

摘要

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. Initial and subsequent UTIs can alter bladder epithelial cell barrier function, which in turn creates an environment more favorable to subsequent infection. 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. 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. Alarmingly, >70% of postmenopausal recurrent UTI patients are either allergic or resistant to TMP-SMX. 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. 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.