Mp23-03 Il-6/stat3 Signaling Is a Host Determinant of Upec Virulence Via Altered Bacterial Invasion and Intracellular Bacterial Community Formation
Year: 2018
Type: article
Abstract: INTRODUCTION AND OBJECTIVES: While acute urinary tract infections (UTI) are easily treated, recurrent UTIs are a prevalent cause of morbidity.No predictive molecular factors which may increase or decrease in an individual's susceptibility to UTI are known, precluding any individualized medicine approach to treatment.Uropathogenic E.coli (UPEC) cause ~90% of all UTIs, and UPEC initiate infection through bacterial -glycan interactions.We and others have hypothesized that endogenous variability in the glycan component of urine may result in differences in host defense factors and could be the molecular basis for variable UTI susceptibility.Knowing the glycosylation status of an individual may eventually indicate their susceptibility to rUTI and enable faster, more appropriate treatment.This study characterizes urine from 4 healthy adult males and 4 females with the aim of defining the large-scale atlas of glycoproteins and the glycans that they harbor.This information facilitates future glycoproteomic discovery studies, identifies novel host defense factors in urine, and is critical for future assessment of individual variations.METHODS: Samples were prepared by a modified filter-aided sample prep (FASP) protocol, reduced and alkylated, digested with trypsin overnight, enriched for glycopeptides, and analyzed using a Q-Exactive mass spectrometer (MS) coupled to a eksigent 400 nano liquid chromatography system.All raw data was searched using an in-house software specifically designed for glycoproteomics (glycoPipe) and Proteome Discoverer 2.1.All glycan, proteins and peptide identifications were filtered to a 1% false-discovery rate.RESULTS: A total of 1391 unique glycopeptides were identified from 94 unique glycoproteins.Among the most clinically relevant high mannose (HM) type glycans, 104 HM glycopeptides on 50 unique sites from 41 glycoproteins were found.This represents the largest known dataset of glycopeptides from urine.Intriguingly, glycoproteins are overrepresented in several pertinent biological pathways.These include complement activation (p-value of 2x10-10), acute phase response signaling (4x10-22) and others.In addition, 47 of these glycoproteins (50% of total) are downstream from at interleukin-6, TGF-b, or lipopolysaccharide, and as such, and may be induced or repressed in response to infection.CONCLUSIONS: A network of putative glycoproteomics host defense factors against UTI has been identified by glycoproteomics.
Source: The Journal of Urology
Authors: Christina Ching, Sudipti Gupta, Brian Becknell
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: bronze
Award: G6912916513
OpenAlex ID: W2796404643