OmpA Is the Critical Component for Escherichia coli Invasion-Induced Astrocyte Activation

Wu, Hsueh Hsia; Yang, Yi Yuan; Hsieh, Wen Shyang; Lee, Chi Hsin; Leu, Sy Jye; Chen, Mei‐Ru

doi:10.1097/nen.0b013e3181a77d1e

Cited by 21 publications

(14 citation statements)

References 51 publications

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“…Although the host cell receptors for these binding events and the matter of how they are involved in the internalization process are currently unknown, it is possible that besides TRP120, other bacterial surface-exposed proteins are associated with bacterial internalization. OmpA may be one such protein, because levels were reduced by CDGA treatment and because the E. coli OmpA ortholog is involved in bacterial invasion of astrocytes and E. coli-induced meningitis (67). One interesting finding in our study is that CDGA treatment and consequent degradation of TRP120 or OmpA did not inhibit E. chaffeensis binding to THP-1 cells, indicating that the remaining proteins are sufficient for bacterial binding but that TRP120 and OmpA are required for efficient internalization.…”

Section: Discussionsupporting

confidence: 47%

Cyclic di-GMP Signaling Regulates Invasion by Ehrlichia chaffeensis of Human Monocytes

et al. 2010

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Cyclic di-GMP (c-di-GMP) is a bacterial second messenger produced by GGDEF domain-containing proteins. The genome of Ehrlichia chaffeensis, an obligatory intracellular bacterium that causes human monocytic ehrlichiosis, encodes a single protein that contains a GGDEF domain, called PleD. In this study, we investigated the effects of c-di-GMP signaling on E. chaffeensis infection of the human monocytic cell line THP-1. Recombinant E. chaffeensis PleD showed diguanylate cyclase activity as it generated c-di-GMP in vitro. Because c-di-GMP is not cell permeable, the c-di-GMP hydrophobic analog 2-O-di(tert-butyldimethylsilyl)-c-di-GMP (CDGA) was used to examine intracellular c-di-GMP signaling. CDGA activity was first tested with Salmonella enterica serovar Typhimurium. CDGA inhibited well-defined c-di-GMP-regulated phenomena, including cellulose synthesis, clumping, and upregulation of csgD and adrA mRNA, indicating that CDGA acts as an antagonist in c-di-GMP signaling. [32 P]c-di-GMP bound several E. chaffeensis native proteins and two E. chaffeensis recombinant I-site proteins, and this binding was blocked by CDGA. Although pretreatment of E. chaffeensis with CDGA did not reduce bacterial binding to THP-1 cells, bacterial internalization was reduced. CDGA facilitated protease-dependent degradation of particular, but not all, bacterial surface-exposed proteins, including TRP120, which is associated with bacterial internalization. Indeed, the serine protease HtrA was detected on the surface of E. chaffeensis, and TRP120 was degraded by treatment of E. chaffeensis with recombinant E. chaffeensis HtrA. Furthermore, anti-HtrA inhibited CDGA-induced TRP120 degradation. Our results suggest that E. chaffeensis invasion is regulated by c-di-GMP signaling, which stabilizes some bacterial surface-exposed proteins against proteases.Ehrlichia chaffeensis causes the potentially fatal infectious disease human monocytic ehrlichiosis. This disease is one of the most prevalent life-threatening tick-borne zoonoses in the United States, but it is less frequently reported to occur in other parts of the world (13, 42). E. chaffeensis is a Gramnegative bacterium that belongs to the order Rickettsiales in the Alphaproteobacteria. To survive, E. chaffeensis must infect eukaryotic host cells, as it lacks most of the genes for the biosynthesis of amino acids and the associated intermediary metabolism (47). E. chaffeensis invades human monocytes and macrophages and replicates in membrane-bound inclusions by inhibiting oxidative and nonoxidative microbicidal mechanisms in these cells (48).Cyclic di-GMP (c-di-GMP) is a bacterial second messenger produced by the GGDEF domain-containing diguanylate cyclase (DGC). c-di-GMP is degraded by EAL or HD-GYP domain-containing c-di-GMP-specific phosphodiesterases (22,29,52,53,55,63). Because GGDEF domain-containing proteins are found in most sequenced bacterial genomes, c-di-GMP signaling is considered to be ubiquitous (15, 28). c-di-GMP inversely regulates the planktonic traits (motility) and communal or...

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Section: Discussionsupporting

confidence: 47%

Cyclic di-GMP Signaling Regulates Invasion by Ehrlichia chaffeensis of Human Monocytes

et al. 2010

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“…To date, very few porins have been shown to be involved in bacterial virulence. This is the case for the OprF homologue OmpA, present in the Enterobacteriaceae family and some other Gammaproteobacteria class members, which contributes to interactions of Acinetobacter baumannii with eukaryotic cells (29), to astrocyte colonization by E. coli (71), and to invasion of human brain microvascular endothelial cells by Cronobacter sakazakii (48). In P. aeruginosa, a role of OM proteins in virulence recently emerged, since the OM protein OprG, an anaerobically induced porin, was shown to contribute to early-stage infections of human bronchial epithelial cells (45).…”

Section: Discussionmentioning

confidence: 99%

Full Virulence of Pseudomonas aeruginosa Requires OprF

et al. 2011

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OprF is a general outer membrane porin of Pseudomonas aeruginosa, a well-known human opportunistic pathogen associated with severe hospital-acquired sepsis and chronic lung infections of cystic fibrosis patients. A multiphenotypic approach, based on the comparative study of a wild-type strain of P. aeruginosa, its isogenic oprF mutant, and an oprF-complemented strain, showed that OprF is required for P. aeruginosa virulence. The absence of OprF results in impaired adhesion to animal cells, secretion of ExoT and ExoS toxins through the type III secretion system (T3SS), and production of the quorum-sensing-dependent virulence factors pyocyanin, elastase, lectin PA-1L, and exotoxin A. Accordingly, in the oprF mutant, production of the signal molecules N-(3-oxododecanoyl)-L-homoserine lactone and N-butanoyl-L-homoserine lactone was found to be reduced and delayed, respectively. Pseudomonas quinolone signal (PQS) production was decreased, while its precursor, 4-hydroxy-2-heptylquinoline (HHQ), accumulated in the cells. Taken together, these results show the involvement of OprF in P. aeruginosa virulence, at least partly through modulation of the quorum-sensing network. This is the first study showing a link between OprF, PQS synthesis, T3SS, and virulence factor production, providing novel insights into virulence expression.

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“…Overexpression of SAA by intestinal epithelial cells in culture can reduce E. coli viability [12], and in in vitro assays SAA can act as an opsonin for various Gram-negative bacteria by binding to the highly expressed outer membrane protein OmpA [9]. Of note, the ability of some E. coli strains to invade host cells and form biofilms is critically dependent upon OmpA [13], [14], [15], [16]. Preferential binding of SAA to OmpA over endogenous host ligands, including high density lipoprotein (HDL) [4], may significantly impact both the host environment and pathogen fitness during the course of an infection.…”

Section: Introductionmentioning

confidence: 99%

Uropathogenic Escherichia coli Induces Serum Amyloid A in Mice following Urinary Tract and Systemic Inoculation

et al. 2012

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Serum amyloid A (SAA) is an acute phase protein involved in the homeostasis of inflammatory responses and appears to be a vital host defense component with protective anti-infective properties. SAA expression remains poorly defined in many tissues, including the urinary tract which often faces bacterial challenge. Urinary tract infections (UTIs) are usually caused by strains of uropathogenic Escherichia coli (UPEC) and frequently occur among otherwise healthy individuals, many of whom experience bouts of recurrent and relapsing infections despite the use of antibiotics. To date, whether SAA is present in the infected urothelium and whether or not the induction of SAA can protect the host against UPEC is unclear. Here we show, using mouse models coupled with immunofluorescence microscopy and quantitative RT-PCR, that delivery of UPEC either directly into the urinary tract via catheterization or systemically via intraperitoneal injection triggers the expression of SAA. As measured by ELISA, serum levels of SAA1/2 were also transiently elevated in response to UTI, but circulating SAA3 levels were only up-regulated substantially following intraperitoneal inoculation of UPEC. In in vitro assays, physiological relevant levels of SAA1/2 did not affect the growth or viability of UPEC, but were able to block biofilm formation by the uropathogens. We suggest that SAA functions as a critical host defense against UTIs, preventing the formation of biofilms both upon and within the urothelium and possibly providing clinicians with a sensitive serological marker for UTI.

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OmpA Is the Critical Component for Escherichia coli Invasion-Induced Astrocyte Activation

Cited by 21 publications

References 51 publications

Cyclic di-GMP Signaling Regulates Invasion by Ehrlichia chaffeensis of Human Monocytes

Cyclic di-GMP Signaling Regulates Invasion by Ehrlichia chaffeensis of Human Monocytes

Full Virulence of Pseudomonas aeruginosa Requires OprF

Uropathogenic Escherichia coli Induces Serum Amyloid A in Mice following Urinary Tract and Systemic Inoculation

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