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Mario Campa - One of the best experts on this subject based on the ideXlab platform.
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reduced human Beta Defensin 3 in individuals with periodontal disease
Journal of Dental Research, 2011Co-Authors: Franca Lisa Brancatisano, Giuseppantonio Maisetta, Semih Esin, Mario Campa, F Barsotti, M Miceli, Mario Gabriele, Maria Rita Giuca, Giovanna BatoniAbstract:The human Beta Defensin 3 (hBD3) is widely expressed in the oral cavity and exerts strong antibacterial and immunomodulatory activities. Hence, we hypothesized that hBD3 could play a protective role in the maintenance of periodontal homeostasis, and that it could be found in gingival crevicular fluid (GCF) of healthy individuals and those with periodontitis at levels correlating with the degree of periodontal health. By using an ELISA assay to quantify hBD3 in GCF, we demonstrated that the peptide is present at levels easily detectable in the majority of healthy individuals, but it is drastically reduced in GCF from those with periodontitis. Furthermore, hBD3 levels inversely correlate with the severity of the disease and the degree of colonization by combinations of bacterial species with elevated periodontopathogenic potential. Both genetic factors and host/bacterial proteases released in diseased sites may be responsible for the observed low/null hBD3 levels in GCF from individuals with periodontitis.
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Evaluation of the inhibitory effects of human serum components on bactericidal activity of human Beta Defensin 3
Peptides, 2007Co-Authors: Giuseppantonio Maisetta, Semih Esin, Mario Campa, Franca Lisa Brancatisano, Walter Florio, Daria Bottai, Mariagrazia Di Luca, Giovanna BatoniAbstract:Abstract Naturally occurring cationic antimicrobial peptides (CAPs) are an essential component of the innate immune system of multicellular organisms. At concentrations generally higher than those found in vivo, most CAPs exhibit strong antibacterial properties in vitro, but their activity may be inhibited by body fluids, a fact that could limit their future use as antimicrobial and/or immunomodulatory agents. In the present study, we evaluated the effects of human serum components on bactericidal activity of the human β-Defensin 3 (hBD-3), a CAP considered particularly promising for future therapeutic employment. Human serum diluted to 20% strongly inhibited the bactericidal activity of the peptide against both the Gram-positive species Staphylococcus aureus and the Gram-negative species Acinetobacter baumannii . Such activity was not restored in serum devoid of salts (dialyzed), pre-treated with protease inhibitors, or subjected to both of these treatments. The addition of physiological concentrations of NaCl, CaCl 2 , and human albumin in the bactericidal assay abolished bactericidal activity of hBD-3 against S. aureus , while it only partially inhibited the activity of the peptide against A. baumannii . Although a proteolytic activity of serum on hBD-3 was demonstrated at the protein level by Western blot, addition of physiological concentrations of trypsin to the bactericidal assay only partially affected the antibacterial properties of the peptide. Altogether, these results demonstrate a major role of mono-divalent cations and serum proteins on inhibition of hBD-3 antibacterial properties and indicate a relative lack in sensitivity of the bactericidal activity of this peptide to trypsin and trypsin-like proteases.
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Human Beta-Defensin-3: a promising antimicrobial peptide.
Mini-Reviews in Medicinal Chemistry, 2006Co-Authors: Giovanna Batoni, Giuseppantonio Maisetta, Semih Esin, Mario CampaAbstract:The field of naturally occurring antimicrobial peptides is a research area rapidly expanding due to the high potential of such molecules as new antimicrobial drugs. In this regard, the human Beta-Defensin-3 is particularly attractive because of its strong antibacterial activity, relative salt-insensitiveness and low toxicity for host cells.
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In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains
Antimicrobial agents and chemotherapy, 2006Co-Authors: Giuseppantonio Maisetta, Giovanna Batoni, Semih Esin, Walter Florio, Daria Bottai, Flavia Favilli, Mario CampaAbstract:The antimicrobial activity of human Beta-Defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.
Giovanna Batoni - One of the best experts on this subject based on the ideXlab platform.
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reduced human Beta Defensin 3 in individuals with periodontal disease
Journal of Dental Research, 2011Co-Authors: Franca Lisa Brancatisano, Giuseppantonio Maisetta, Semih Esin, Mario Campa, F Barsotti, M Miceli, Mario Gabriele, Maria Rita Giuca, Giovanna BatoniAbstract:The human Beta Defensin 3 (hBD3) is widely expressed in the oral cavity and exerts strong antibacterial and immunomodulatory activities. Hence, we hypothesized that hBD3 could play a protective role in the maintenance of periodontal homeostasis, and that it could be found in gingival crevicular fluid (GCF) of healthy individuals and those with periodontitis at levels correlating with the degree of periodontal health. By using an ELISA assay to quantify hBD3 in GCF, we demonstrated that the peptide is present at levels easily detectable in the majority of healthy individuals, but it is drastically reduced in GCF from those with periodontitis. Furthermore, hBD3 levels inversely correlate with the severity of the disease and the degree of colonization by combinations of bacterial species with elevated periodontopathogenic potential. Both genetic factors and host/bacterial proteases released in diseased sites may be responsible for the observed low/null hBD3 levels in GCF from individuals with periodontitis.
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Evaluation of the inhibitory effects of human serum components on bactericidal activity of human Beta Defensin 3
Peptides, 2007Co-Authors: Giuseppantonio Maisetta, Semih Esin, Mario Campa, Franca Lisa Brancatisano, Walter Florio, Daria Bottai, Mariagrazia Di Luca, Giovanna BatoniAbstract:Abstract Naturally occurring cationic antimicrobial peptides (CAPs) are an essential component of the innate immune system of multicellular organisms. At concentrations generally higher than those found in vivo, most CAPs exhibit strong antibacterial properties in vitro, but their activity may be inhibited by body fluids, a fact that could limit their future use as antimicrobial and/or immunomodulatory agents. In the present study, we evaluated the effects of human serum components on bactericidal activity of the human β-Defensin 3 (hBD-3), a CAP considered particularly promising for future therapeutic employment. Human serum diluted to 20% strongly inhibited the bactericidal activity of the peptide against both the Gram-positive species Staphylococcus aureus and the Gram-negative species Acinetobacter baumannii . Such activity was not restored in serum devoid of salts (dialyzed), pre-treated with protease inhibitors, or subjected to both of these treatments. The addition of physiological concentrations of NaCl, CaCl 2 , and human albumin in the bactericidal assay abolished bactericidal activity of hBD-3 against S. aureus , while it only partially inhibited the activity of the peptide against A. baumannii . Although a proteolytic activity of serum on hBD-3 was demonstrated at the protein level by Western blot, addition of physiological concentrations of trypsin to the bactericidal assay only partially affected the antibacterial properties of the peptide. Altogether, these results demonstrate a major role of mono-divalent cations and serum proteins on inhibition of hBD-3 antibacterial properties and indicate a relative lack in sensitivity of the bactericidal activity of this peptide to trypsin and trypsin-like proteases.
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Human Beta-Defensin-3: a promising antimicrobial peptide.
Mini-Reviews in Medicinal Chemistry, 2006Co-Authors: Giovanna Batoni, Giuseppantonio Maisetta, Semih Esin, Mario CampaAbstract:The field of naturally occurring antimicrobial peptides is a research area rapidly expanding due to the high potential of such molecules as new antimicrobial drugs. In this regard, the human Beta-Defensin-3 is particularly attractive because of its strong antibacterial activity, relative salt-insensitiveness and low toxicity for host cells.
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In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains
Antimicrobial agents and chemotherapy, 2006Co-Authors: Giuseppantonio Maisetta, Giovanna Batoni, Semih Esin, Walter Florio, Daria Bottai, Flavia Favilli, Mario CampaAbstract:The antimicrobial activity of human Beta-Defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.
De Yang - One of the best experts on this subject based on the ideXlab platform.
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antifungal activity of recombinant mouse Beta Defensin 3
Letters in Applied Microbiology, 2010Co-Authors: Yongmei Jiang, Baoning Wang, De Yang, X. Yang, Feng Liu, Yu-zhong Wang, Zhonghua JiangAbstract:Aims: To identify the presence of mouse β-Defensin 3 (Mbd3) (the human homologue of β-Defensin 2) in different tissues and to define the antimicrobial properties of recombinant MBD3 (rMBD3) against a panel of human pathogens. Methods and Results: Mbd3 gene expression in different mouse tissues before or after lipopolysaccharide (LPS) injection was compared by semi-quantitative RT-PCR. This analysis demonstrated that epithelial and mucosal tissues expressed Mbd3 independent of LPS stimulation. Evaluation of the antimicrobial properties of recombinant rMBD3 was determined by assessing the median inhibition concentration (IC50), minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)/minimal fungicidal concentration (MFC) against various human pathogens. Conclusion: Mbd3 gene expression by epithelial and mucosal tissues suggested that MBD3 likely plays an early defensive role against microbial infections. This activity was most significant against filamentous fungi. Significance and Impact of the Study: The data presented in this report suggested that formulations containing rMBD3 and related molecules could serve to treat fungal and bacterial infections.
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Antifungal activity of recombinant mouse Beta‐Defensin 3
Letters in applied microbiology, 2010Co-Authors: Yongmei Jiang, Yueling Wang, Baoning Wang, De Yang, X. Yang, Feng Liu, Zhonghua JiangAbstract:Aims: To identify the presence of mouse β-Defensin 3 (Mbd3) (the human homologue of β-Defensin 2) in different tissues and to define the antimicrobial properties of recombinant MBD3 (rMBD3) against a panel of human pathogens. Methods and Results: Mbd3 gene expression in different mouse tissues before or after lipopolysaccharide (LPS) injection was compared by semi-quantitative RT-PCR. This analysis demonstrated that epithelial and mucosal tissues expressed Mbd3 independent of LPS stimulation. Evaluation of the antimicrobial properties of recombinant rMBD3 was determined by assessing the median inhibition concentration (IC50), minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)/minimal fungicidal concentration (MFC) against various human pathogens. Conclusion: Mbd3 gene expression by epithelial and mucosal tissues suggested that MBD3 likely plays an early defensive role against microbial infections. This activity was most significant against filamentous fungi. Significance and Impact of the Study: The data presented in this report suggested that formulations containing rMBD3 and related molecules could serve to treat fungal and bacterial infections.
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Antifungal activity of recombinant mouse Beta‐Defensin 3
Letters in applied microbiology, 2010Co-Authors: Yongmei Jiang, Baoning Wang, De Yang, X. Yang, Feng Liu, Yu-zhong Wang, Zhonghua JiangAbstract:To identify the presence of mouse Beta-Defensin 3 (Mbd3) (the human homologue of Beta-Defensin 2) in different tissues and to define the antimicrobial properties of recombinant MBD3 (rMBD3) against a panel of human pathogens. Mbd3 gene expression in different mouse tissues before or after lipopolysaccharide (LPS) injection was compared by semi-quantitative RT-PCR. This analysis demonstrated that epithelial and mucosal tissues expressed Mbd3 independent of LPS stimulation. Evaluation of the antimicrobial properties of recombinant rMBD3 was determined by assessing the median inhibition concentration (IC(50)), minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)/minimal fungicidal concentration (MFC) against various human pathogens. Mbd3 gene expression by epithelial and mucosal tissues suggested that MBD3 likely plays an early defensive role against microbial infections. This activity was most significant against filamentous fungi. The data presented in this report suggested that formulations containing rMBD3 and related molecules could serve to treat fungal and bacterial infections.
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Expression of mouse Beta-Defensin-3 in MDCK cells and its anti-influenza-virus activity.
Archives of virology, 2009Co-Authors: Yan Jiang, Zhonghua Jiang, Yueling Wang, Baoning Wang, Yu Kuang, Tianxiang Gong, De YangAbstract:Influenza (flu) pandemics have presented a threat to human health in the past century. Because of outbreaks of avian flu in humans in some developing countries in recent years, humans are more eager to find a way to control flu. Mammalian Beta-Defensins (β-Defensins) are associated primarily with mucosal and skin innate immunity. Previous studies have demonstrated antimicrobial properties of a variety of Defensin peptides. We have identified the presence of mouse β-Defensin 1, 2, and 3 genes (Mbd-1, 2, and 3) in trachea and lung tissues by RT-PCR before and after infection with influenza virus. We constructed a eukaryotic expression plasmid containing Mbd-3, pcDNA 3.1(+)/MBD-3, and the plasmid was introduced into Madin-Darby canine kidney (MDCK) cells by transfection. The expression of Mbd-3 in MDCK cells was verified by immunofluorescence test, RT-PCR, and Western blot. The pcDNA 3.1(+)/MBD-3 plasmid was injected into mice to observe its effect against influenza A virus (IAV) in vivo. Mouse β-Defensin genes could be expressed in trachea and lung tissues before IAV infection, but expression of Mbd-2 and Mbd-3 was increased significantly after IAV infection. The survival rate of mice with MBD-3 against IAV challenge was 71.43%, and MDCK cells with MBD-3 could clearly inhibit IAV replication. The results demonstrated that mouse β-Defensins possess anti-influenza virus activity, suggesting that mouse β-Defensins might be used as agents to prevent and treat influenza.
Giuseppantonio Maisetta - One of the best experts on this subject based on the ideXlab platform.
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reduced human Beta Defensin 3 in individuals with periodontal disease
Journal of Dental Research, 2011Co-Authors: Franca Lisa Brancatisano, Giuseppantonio Maisetta, Semih Esin, Mario Campa, F Barsotti, M Miceli, Mario Gabriele, Maria Rita Giuca, Giovanna BatoniAbstract:The human Beta Defensin 3 (hBD3) is widely expressed in the oral cavity and exerts strong antibacterial and immunomodulatory activities. Hence, we hypothesized that hBD3 could play a protective role in the maintenance of periodontal homeostasis, and that it could be found in gingival crevicular fluid (GCF) of healthy individuals and those with periodontitis at levels correlating with the degree of periodontal health. By using an ELISA assay to quantify hBD3 in GCF, we demonstrated that the peptide is present at levels easily detectable in the majority of healthy individuals, but it is drastically reduced in GCF from those with periodontitis. Furthermore, hBD3 levels inversely correlate with the severity of the disease and the degree of colonization by combinations of bacterial species with elevated periodontopathogenic potential. Both genetic factors and host/bacterial proteases released in diseased sites may be responsible for the observed low/null hBD3 levels in GCF from individuals with periodontitis.
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Evaluation of the inhibitory effects of human serum components on bactericidal activity of human Beta Defensin 3
Peptides, 2007Co-Authors: Giuseppantonio Maisetta, Semih Esin, Mario Campa, Franca Lisa Brancatisano, Walter Florio, Daria Bottai, Mariagrazia Di Luca, Giovanna BatoniAbstract:Abstract Naturally occurring cationic antimicrobial peptides (CAPs) are an essential component of the innate immune system of multicellular organisms. At concentrations generally higher than those found in vivo, most CAPs exhibit strong antibacterial properties in vitro, but their activity may be inhibited by body fluids, a fact that could limit their future use as antimicrobial and/or immunomodulatory agents. In the present study, we evaluated the effects of human serum components on bactericidal activity of the human β-Defensin 3 (hBD-3), a CAP considered particularly promising for future therapeutic employment. Human serum diluted to 20% strongly inhibited the bactericidal activity of the peptide against both the Gram-positive species Staphylococcus aureus and the Gram-negative species Acinetobacter baumannii . Such activity was not restored in serum devoid of salts (dialyzed), pre-treated with protease inhibitors, or subjected to both of these treatments. The addition of physiological concentrations of NaCl, CaCl 2 , and human albumin in the bactericidal assay abolished bactericidal activity of hBD-3 against S. aureus , while it only partially inhibited the activity of the peptide against A. baumannii . Although a proteolytic activity of serum on hBD-3 was demonstrated at the protein level by Western blot, addition of physiological concentrations of trypsin to the bactericidal assay only partially affected the antibacterial properties of the peptide. Altogether, these results demonstrate a major role of mono-divalent cations and serum proteins on inhibition of hBD-3 antibacterial properties and indicate a relative lack in sensitivity of the bactericidal activity of this peptide to trypsin and trypsin-like proteases.
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Human Beta-Defensin-3: a promising antimicrobial peptide.
Mini-Reviews in Medicinal Chemistry, 2006Co-Authors: Giovanna Batoni, Giuseppantonio Maisetta, Semih Esin, Mario CampaAbstract:The field of naturally occurring antimicrobial peptides is a research area rapidly expanding due to the high potential of such molecules as new antimicrobial drugs. In this regard, the human Beta-Defensin-3 is particularly attractive because of its strong antibacterial activity, relative salt-insensitiveness and low toxicity for host cells.
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In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains
Antimicrobial agents and chemotherapy, 2006Co-Authors: Giuseppantonio Maisetta, Giovanna Batoni, Semih Esin, Walter Florio, Daria Bottai, Flavia Favilli, Mario CampaAbstract:The antimicrobial activity of human Beta-Defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.
Rainer Podschun - One of the best experts on this subject based on the ideXlab platform.
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influence of disulfide bonds in human Beta Defensin 3 on its strain specific activity against gram negative bacteria
Biochimica et Biophysica Acta, 2020Co-Authors: Christian Nehls, Rainer Podschun, Sabine Schubert, Jürgen Harder, Arne Bohling, Joachim Grotzinger, Andra B Schromm, Henning Fedders, Matthias Leippe, Yani KaconisAbstract:Abstract Antimicrobial peptides (AMPs) play an important role in the host defense against various microbes. One of the most efficient human AMPs is the human Beta Defensin-3 (hBD-3) which is produced by, e.g. keratinocytes and lung epithelial cells. However, the structure-function relationship for AMPs and in particular for Defensins with their typical three disulfide bonds is still poorly understood. In this study the importance of the three disulfide bonds for the activity of the AMPs is investigated with biological assays and with biophysical experiments utilizing different membrane reconstitution systems. The activities of natural hBD-3, hBD-3-c (cyclic variant with one disulfide bond), and hBD-3-l (linear variant without disulfide bonds) and fragments thereof were tested against specific Gram-negative bacteria. Furthermore, hemolytic and cytotoxic activities were analyzed as well as the potency to neutralize immune cell stimulation of lipopolysaccharide (LPS). Experiments using reconstituted lipid matrices composed of phospholipids or LPS purified from the respective Gram-negative bacteria, showed that the membrane activity of all three hBD-3 peptides is decisive for their capability to kill bacteria and to neutralize LPS. In most of the test systems the linear hBD-3-l showed the highest activity. It was also the only peptide significantly active against polymyxin B-resistant Proteus mirabilis R45. However, the stability of hBD-3 against protease activity decreases with decreasing number of disulfide bonds. This study demonstrates that the refining of AMP structures can generate more active compounds against certain strains.
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thrombocytes are effectors of the innate immune system releasing human Beta Defensin 3
Injury-international Journal of The Care of The Injured, 2011Co-Authors: Mersedeh Tohidnezhad, Rainer Podschun, Thomas Pufe, Deike Varoga, A. Seekamp, Christoph Jan Wruck, Larsove Brandenburg, Sebastian LipprossAbstract:Abstract Background Thrombocyte concentrate i.e. platelet-rich plasma (PRP) has become a popular adjunct for many surgical procedures. It is believed to improve bone and soft tissue healing. Recently antimicrobial effects of the autologous preparation were reported by several groups. In this study we investigated the antimicrobial effect of PRP against gram-negative microbes which frequently cause severe complications in orthopaedic trauma surgery. Methods Platelet-rich plasma was produced from liquid preserved thrombocyte concentrates. ELISA, Western blot and immunohistochemistry were preformed to investigate the release and content of platelet concentrates. A radial diffusion assay was used to detect antimicrobial effects of PRP. Results We detected the human Beta Defensin-3 in bactericidal concentrations in platelet preparations by ELISA, Western blot and immunohistochemistry. In antimicrobial testing we demonstrated effective inhibition of Escherichia coli (ATCC 11303), Bacterium megaterium (ATCC 14581), Klebsiella pneumoniae (ATCC 13883), Enterococcus faecalis (ATCC 29212) and Proteus mirabilis (ATCC21100). Conclusion With this study we demonstrate antimicrobial action of a popular adjunct for orthopaedic and trauma surgery against gram-positive and gram-negative bacteria. We have identified a possible mechanism of action via the secretion of HBD-3 as a first line defence in contaminated wounds and in elective application of PRP. This finding supports a broader spectrum of clinical indications for an autologous platelet preparation.
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Mouse Beta-Defensin-14, an Antimicrobial Ortholog of Human Beta-Defensin-3
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Kerstin Hinrichsen, Rainer Podschun, Sabine Schubert, Jens M. Schröder, Jürgen Harder, Ehrhardt ProkschAbstract:Searching the database for mouse homologs of the antimicrobial peptide human Beta-Defensin-3 (hBD-3) revealed highest identity (69%) to mouse Beta-Defensin-14 (mBD-14). Recombinant mBD-14 exhibited broad-spectrum, nanomolar microbicidal activity. Treatment of keratinocytes with gamma interferon or transforming growth factor alpha increased mBD-14 gene expression. These data suggest that mBD-14 is the functional ortholog of hBD-3.
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Burkholderia Is Highly Resistant to Human Beta-Defensin 3
Antimicrobial Agents and Chemotherapy, 2003Co-Authors: Hany Sahly, Sabine Schubert, Jens M. Schröder, Jürgen Harder, Peter Rautenberg, Uwe Ullmann, Rainer PodschunAbstract:The bactericidal activity of the novel Beta-Defensin hBD-3 against 28 species and 55 strains of gram-positive cocci and gram-negative fermentative and nonfermentative rods was tested. All strains proved to be highly or intermediately susceptible to hBD-3 (minimal bactericidal concentration [MBC], ≤50 μg/ml), except for Burkholderia cepacia, for all 23 tested strains of which MBCs were >100 μg/ml.