In vitro bactericidal activity of human β-defensin 2 against nosocomial strains

Routsias, John G.; Karagounis, Panagiotis; Parvulesku, Georgeta; Nj, Legakis; Tsakris, Athanassios

doi:10.1016/j.peptides.2010.06.010

Cited by 50 publications

(37 citation statements)

References 36 publications

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“…One such mechanism involves antimicrobial peptide production (e.g., ␤-defensin 2 [BD2]). 〉D2 has been reported to exhibit strong bactericidal activity even against multidrug-resistant A. baumannii (31). Moreover, A. baumannii infection has been shown to upregulate ␤-defensin 2 levels in airway epithelial cells (8), but the underlying mechanism/signaling pathway is not yet known.…”

Section: Resultsmentioning

confidence: 99%

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The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

et al. 2014

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Acinetobacter baumannii is a major extensively drug-resistant lethal human nosocomial bacterium. However, the host innate immune mechanisms controlling A. baumannii are not well understood. Although viewed as an extracellular pathogen, A. baumannii can also invade and survive intracellularly. However, whether host innate immune pathways sensing intracellular bacteria contribute to immunity against A. baumannii is not known. Here, we provide evidence for the first time that intracellular antibacterial innate immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in the sensing and clearance of A. baumannii by human airway epithelial cells in vitro. A. baumannii infection upregulated Rip2 expression. Silencing of Nod1, Nod2, and Rip2 expression profoundly increased intracellular invasion and prolonged the multiplication and survival of A. baumannii in lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control of A. baumannii infection of human macrophages, indicating that they play cell type-specific roles. The Nod1/2-Rip2 axis was needed for A. baumannii infection-induced activation of NF-B but not mitogen-activated protein kinases. Moreover, the Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to A. baumannii infection. Mechanistic studies showed that the Nod1/2 pathway contributed to the innate control of A. baumannii infection through the production of ␤-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control of A. baumannii and may contribute to the development of effective immune therapeutics and vaccines against A. baumannii.

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Section: Resultsmentioning

confidence: 99%

“…A. baumannii is no exception. Previous reports have shown that BD2 is highly effective in killing A. baumannii, including multidrug-resistant strains (31). In addition, A. baumannii is known to upregulate beta defensin 2 levels in airway epithelial cells, although the signaling pathways involved in this process are not well defined (8).…”

Section: Discussionmentioning

confidence: 99%

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

et al. 2014

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“…Our results demonstrated that hBD-2 induces selective accumulation of purine nucleosides, including Ado, which is an important and wellstudied immunomodulator, validating our initial hypothesis. The experimental setup was designed by considering the effective concentrations reported for hBD-2, ranging from 10 to 50 g/ml (24)(25)(26). In a physiologic context, the precise local concentrations of peptide at the site of defensin action are not known, and it is reported that most of the antimicrobial activity secreted by the intestinal mucosa is retained in the mucus layer, contributing to uneven distribution and variable local concentrations (27).…”

Section: Discussionmentioning

confidence: 99%

Human β-Defensin 2 Induces Extracellular Accumulation of Adenosine in Escherichia coli

Estrela

Rohde

Gutierrez

et al. 2013

Antimicrob Agents Chemother

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Human ␤-defensins are host defense peptides performing antimicrobial as well as immunomodulatory functions. The present study investigated whether treatment of Escherichia coli with human ␤-defensin 2 could generate extracellular molecules of relevance for immune regulation. Mass spectrometry analysis of bacterial supernatants detected the accumulation of purine nucleosides triggered by ␤-defensin 2 treatment. Other cationic antimicrobial peptides tested presented variable outcomes with regard to extracellular adenosine accumulation; human ␤-defensin 2 was the most efficient at inducing this response. Structural and biochemical evidence indicated that a mechanism other than plain lysis was involved in the observed phenomenon. By use of isotope ( 13 C) labeling, extracellular adenosine was found to be derived from preexistent RNA, and a direct interaction between the peptide and bacterial nucleic acid was documented for the first time for ␤-defensin 2. Taken together, the data suggest that defensin activity on a bacterial target may alter local levels of adenosine, a well-known immunomodulator influencing inflammatory processes. Human ␤-defensins (hBD) are cationic antimicrobial peptides produced predominantly by epithelial cells (1). Notably, in the intestine, an environment populated by a dense and rich microbial community, epithelial defensins reinforce the host innate defense (2). These peptides are normally expressed at low basal levels, but hBD-2 and -3 can be upregulated by a variety of microbial and inflammatory stimuli (3, 4). In particular, altered hBD-2 expression has been reported to correlate with the development of intestinal inflammation (5, 6). On the other hand, intestinal inflammation has been associated with alterations in the microbiota-for example, with shifts in the relative abundance of Proteobacteria, such as Escherichia coli (7,8). Elucidating how the interaction between hBD and their bacterial targets impact inflammatory processes can aid our understanding of host-microbe networking in health and disease.The most-studied mechanism of action of cationic antimicrobial peptides involves membrane permeabilization with eventual cell lysis; however, other mechanisms and cellular targets have been described for many peptides, including human defensins (9-12). Moreover, in addition to their antimicrobial activity, manifold immunomodulatory properties of defensins have been reported, and many of these reports describe direct effects on immune cells and cytokine expression (13-15). In some cases, the interaction of peptides with bacterial components is implicated in their immunomodulatory effects (16,17). In this context, the present study hypothesized that hBD-2 activity on E. coli could result in the generation of extracellular mediators with relevance for immunomodulation. MATERIALS AND METHODSChemicals. Lyophilized synthetic human ␤-defensin 2, human ␤-defensin 3, and human ␣-defensin 5 were purchased from the Peptide Institute Inc., sheep myeloid antimicrobial peptide 29 (SMAP-29) from AnaSpe...

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“…22 Patients with 25(OH) D levels less than 20 ng/mL may be unable to fully express cathelicidin, 18 which could be associated with increased susceptibility to nosocomial infections such as pneumonia, sepsis and central line infections. 21 Another antimicrobial peptide, human beta-defensin-2 (HBD)-2, may have special utility in multidrug resistant microbes from in vitro studies, 27 although its overall role is less clearly defined. In lesions observed in psoriasis and atopic dermatitis, vitamin D promoted increased cathelicidin 28 but decreased beta-defensin-2 production.…”

Section: Antimicrobial Efficacy Against Different Infective Agentsmentioning

confidence: 99%

Antimicrobial implications of vitamin D

Youssef

Miller

Elabbassi

et al. 2011

Dermato-Endocrinology

171

128

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In vitro bactericidal activity of human β-defensin 2 against nosocomial strains

Cited by 50 publications

References 36 publications

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

Human β-Defensin 2 Induces Extracellular Accumulation of Adenosine in Escherichia coli

Antimicrobial implications of vitamin D

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