Natural Killer Cell-Mediated Host Defense against Uropathogenic E. coli Is Counteracted by Bacterial HemolysinA-Dependent Killing of NK Cells

Gur, Chamutal; Coppenhagen-Glazer, Shunit; Rosenberg, Shilo; Yamin, Rachel; Enk, Jonatan; Glasner, Ariella; Bar-On, Yotam; Fleissig, Omer; Naor, Ronit; Abed, Jawad; Mevorach, Dror; Granot, Zvi; Bachrach, Gilad; Mandelboim, Ofer

doi:10.1016/j.chom.2013.11.004

Cited by 59 publications

(59 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). The hly-encoded alpha hemolysin was reported to kill host cells (17), leading us to speculate that the cell death caused by the type I killers was due to alpha hemolysin. As speculated, all type I killers induced hemolysis but none of type I non-killers and other E. coli isolates did so (Fig.…”

Section: E Coli Is Classified Into Four Types Based On Fimh Mutationmentioning

confidence: 99%

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

Tang

et al. 2016

Cancer Research

View full text Add to dashboard Cite

show abstract

Section: E Coli Is Classified Into Four Types Based On Fimh Mutationmentioning

confidence: 99%

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

Tang

et al. 2016

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Using the Ncr1 gfp/gfp mice, it was revealed that Ncr1 is involved in controlling influenza virus infections (5,22,25), tumor and metastases eradication (6,7,10,24), the development of type I and type II diabetes (11,23,26,27), liver fibrosis (28), and bacterial infections (3,29). In all of these studies, the activity of the Ncr1 gfp/gfp NK cells was impaired in an Ncr1-dependent manner.…”

mentioning

confidence: 99%

Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé

Glasner¹,

Šimić

Miklić

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

NK cells kill various cells using activating receptors, such as the natural cytotoxicity receptors (NCRs). NKp46 is a major NCR and is the only NCR expressed in mice (denoted Ncr1). Using Ncr1-deficient mice (Ncr1gfp/pfp) we demonstrated that Ncr1 controls various pathologies, and that in its absence Ncr1-related functions are impaired. In 2012, another Ncr1-related mouse was generated, named Noé, in which a random mutation, W32R, in position 32, impaired the Ncr1-Noé cell surface expression. Interestingly, in the Noé mice, Ncr1-dependent deficiencies were not observed. Additionally, the Noé-NK cells were hyperactivated, probably due to increased Helios expression, and the Noé mice demonstrate increased clearance of influenza and murine CMV. In contrast, in the Ncr1gfp/pfp mice infection with influenza was lethal and we show in the present study no difference in murine CMV infection between Ncr1gfp/pfp and wild-type (WT) mice. Because the foremost difference between the Noé and Ncr1gfp/gfp mice is the presence of a mutated Ncr1-Noé protein, we studied its properties. We show that Ncr1-Noé and various other Ncr1 mutants in position 32 can be expressed on the surface, albeit slowly and unstably, and that ligand recognition and function of the various Ncr1-Noé is similar to the WT Ncr1. We further show that the glycosylation pattern of Ncr1-Noé is aberrant, that the Ncr1-Noé proteins accumulate in the endoplasmic reticulum, and that the expression of Ncr1-Noé proteins, but not WT Ncr1, leads to increased Helios expression. Thus, we suggest that the NK hyperactivated phenotype observed in the Noé mice might result from the presence of the Ncr1-Noé protein.

show abstract

“…RTX proteins are typically thought of as toxins that are secreted through a type 1 secretion system and diffuse away from the bacterium to mediate effects on the host. This is exemplified by the family prototype ␣-hemolysin (40)(41)(42)(43)(44)(45)(46). However, adhesins that are secreted in the same manner but that remain associated with the bacterial cell surface are a growing group of RTX proteins composed of at least six other well-characterized members (47).…”

mentioning

confidence: 99%

A Conserved PapB Family Member, TosR, Regulates Expression of the Uropathogenic Escherichia coli RTX Nonfimbrial Adhesin TosA while Conserved LuxR Family Members TosE and TosF Suppress Motility

2014

View full text Add to dashboard Cite

A heterogeneous subset of extraintestinal pathogenic Escherichia coli (ExPEC) strains, referred to as uropathogenic E. coli (UPEC), causes most uncomplicated urinary tract infections. However, no core set of virulence factors exists among UPEC strains. Instead, the focus of the analysis of urovirulence has shifted to studying broad classes of virulence factors and the interactions between them. For example, the RTX nonfimbrial adhesin TosA mediates adherence to host cells derived from the upper urinary tract. The associated tos operon is well expressed in vivo but poorly expressed in vitro and encodes TosCBD, a predicted type 1 secretion system. TosR and TosEF are PapB and LuxR family transcription factors, respectively; however, no role has been assigned to these potential regulators. Thus, the focus of this study was to determine how TosR and TosEF regulate tosA and affect the reciprocal expression of adhesins and flagella. Among a collection of sequenced UPEC strains, 32% (101/317) were found to encode TosA, and nearly all strains (91% [92/101]) simultaneously carried the putative regulatory genes. Deletion of tosR alleviates tosA repression. The tos promoter was localized upstream of tosR using transcriptional fusions of putative promoter regions with lacZ. TosR binds to this region, affecting a gel shift. A 100-bp fragment 220 to 319 bp upstream of tosR inhibits binding, suggesting localization of the TosR binding site. TosEF, on the other hand, downmodulate motility when overexpressed by preventing the expression of fliC, encoding flagellin. Deletion of tosEF increased motility. Thus, we present an additional example of the reciprocal control of adherence and motility. U rinary tract infections (UTIs) are the second most common bacterial infection in humans (1). UTIs can be classified as complicated or uncomplicated infections. Uncomplicated UTIs, occurring in otherwise healthy individuals, are self-limited infections of the bladder, referred to as cystitis (2-4). However, upon bacterial ascension into the kidney, a more serious infection referred to as pyelonephritis can develop (2, 4). Pyelonephritis, in turn, can lead to the development of bacteremia and sometimes fatal urosepsis (5, 6).UTIs normally occur when uropathogens that colonize the intestine alongside commensal organisms gain access to the periurethral area and then ascend to the urinary bladder (7,8). A heterogeneous subset of extraintestinal pathogenic Escherichia coli (ExPEC) strains, referred to as uropathogenic E. coli (UPEC), causes the overwhelming majority of uncomplicated UTIs (4). UPEC strains carry a battery of virulence factors, including adhesins, toxins, and iron acquisition systems, which promote uropathogenesis (9, 10). However, no core set of virulence factors has been identified. Instead, any given UPEC strain appears to use various virulence factors from these three classes of virulence determinants to colonize the urinary tract (11,12). This thesis requires that we consider established, newly discovered, and putative virule...

show abstract

Natural Killer Cell-Mediated Host Defense against Uropathogenic E. coli Is Counteracted by Bacterial HemolysinA-Dependent Killing of NK Cells

Cited by 59 publications

References 33 publications

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé

A Conserved PapB Family Member, TosR, Regulates Expression of the Uropathogenic Escherichia coli RTX Nonfimbrial Adhesin TosA while Conserved LuxR Family Members TosE and TosF Suppress Motility

Contact Info

Product

Resources

About