Characterization of pathogenicity and chemical signaling of prototype strains and clinical samples of uropathogenic Escherichia coli against compound LED209

Abstract

Urinary tract infections (UTIs) are common worldwide, with Uropathogenic Escherichia coli (UPEC) being the pathogen responsible for most infections, leading to the development of cystitis and acute pyelonephritis, in addition to being responsible for 35-45 % of cases of Acute Renal Failure (ARF). The classical virulence factors of UPEC are linked to the expression of fimbriae P, ±-hemolysin, aerobactin, resistance to serum and encapsulation. The chemical signaling facilitating the colonization process and establishment of the pathogenesis through factors with mediate inter- and intra-kingdom communication. The two-component QseBC system is able to recognize signals produced by the host, such as adrenergic hormones epinephrine (Epi) and norepinephrine (NE), as well as signaling molecules produced by other bacteria, such as the auto-inducer-3 (AI-3). which may regulate and activate the expression of pathogen virulence genes. The LED209 is a molecule that was developed with the purpose of blocking such a signaling pathway, inhibiting the transcription of virulence factors, not interfering with bacterial growth, but making it difficult to colonize and establish the disease. The aim of the present project is investigate in vitro and in vivo how the chemical signaling via QseBC assists in the pathogenesis and virulence of prototype strains EC958, UTI89 and CFT073, as well as recent clinical isolates from the State of São Paulo of UPEC strains, also employing the compound LED209 for blocking this pathway. (AU)