Fig. 3 |. Emerging and potential antibiotic-conserving therapeutics for pyelonephritis.

a, Vaccines induce immunity against uropathogenic Escherichia coli (UPEC) bacterial antigens including adhesins and polysaccharide antigens, such as FimH and lipopolysaccharide (LPS), respectively. Vaccines can also induce immunity against iron receptors. Exogenous mannose or its derivatives, pilicides and cranberry extracts can reduce UPEC binding to host cells. Gepotidacin is a novel antibiotic with a dual-targeting mechanism of action, disrupting both DNA gyrase and topoisomerase IV in bacteria. Probiotics can prevent UPEC attachment to host cells by altering the microenvironment, including pH. Bacteriophages can inhibit biofilm formation and induce lysis of cells that they infect. Antimicrobial peptides (AMPs) are small, cationic peptides that can directly kill bacteria by disrupting their cell membranes or by sequestering metal ions that are required for bacterial enzyme activity. b, Host defences against urinary tract infections (UTIs) can be boosted in a number of ways. Cholesterol targeting drugs can prevent UPEC from utilizing lipid rafts to gain entry into host cells. Immunomodulation of pro-inflammatory factors including interferon regulatory factor 7 (Irf7) has been shown to reduce pyelonephritis in rodent models (dashed line). Additionally, hormones including oestrogen, insulin and vasopressin suppress the inflammatory responses that contribute to pyelonephritis and strengthen the epithelial barrier. These hormones may also boost expression of AMPs. Finally, histone deacetylase inhibitors (HDACi) increase AMP production and reduce UTIs in rodent and cell-culture models. siRNA, small interfering RNA.