Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics.

Isak Demirel,Ignacio Rangel,Katarina Persson,Ulrika Petersson,Robert Kruse

doi:10.3389/fmicb.2017.01058

Isak Demirel, Ignacio Rangel + Show 3 more

Open Access

https://doi.org/10.3389/fmicb.2017.01058

Copy DOI

Journal: Frontiers in microbiology	Publication Date: Jun 13, 2017
Citations: 5	License type: cc-by

Affiliation: Örebro University

Abstract

It is known that an ineffective antibiotic treatment can induce morphological shifts in uropathogenic Escherichia coli (UPEC) but the virulence properties during these shifts remain to be studied. The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL)-producing UPEC (ESBL019) during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. Microarray results showed that the different morphological states of ESBL019 had significant transcriptional alterations of a large number of genes (Transition; 7%, Filamentation; 32%, and Reverted 19% of the entities on the array). All three morphological states of ESBL019 were associated with a decreased energy metabolism, altered iron acquisition systems and altered adhesion expression. In addition, genes associated with LPS synthesis and bacterial motility was also altered in all the morphological states. Furthermore, the transition state induced a significantly higher release of TNF-α from bladder epithelial cells compared to all other morphologies, while the reverted state was unable to induce TNF-α release. Our findings show that the morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.

Highlights

Urinary tract infections (UTIs) are one of the most common bacterial infections
The aim of the present study was to investigate changes in global gene expression patterns and in virulence factor-associated genes in extended spectrum beta-lactamase (ESBL)-producing uropathogenic Escherichia coli (UPEC) during the morphologic transitions induced by ineffective antibiotics in the presence of human primary bladder epithelial cells
In the ESBL019 Transition state, close to 7% of the entities on the array were altered, 32% for ESBL019 Filamented and 19% for ESBL019 Reverted. It appears that the morphological plasticity of UPEC is associated with an extensive flux in the transcriptome of the bacteria and especially in the filamented state

Summary

Introduction

Urinary tract infections (UTIs) are one of the most common bacterial infections. UTI is especially common in women as nearly half of all women will be infected during their lifetime (Foxman, 2003). After the resolution of an active infection non-replicating bacteria can remain within vesicles in deeper layers of the urothelium as quiescent intracellular reservoirs (QIRs) (Mysorekar and Hultgren, 2006). These QIRs can remain quiescent for several months without eliciting an inflammatory response. Filamentation can be induced by components of an activated host defense system (Justice et al, 2006), shear stress (Khandige et al, 2016) and in response to treatment with different beta-lactam antibiotics, in particular, aminothiazolyl cephalosporins like ceftibuten. Knowledge of the virulence factors expressed by different morphological forms of UPEC may be used to devise novel therapeutic strategies to obstruct these virulence factors in order to inhibit pathogenesis

Objectives

Methods

Results

Conclusion