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Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37
Published on Oct 3, 2002in Molecular Microbiology 3.82
· DOI :10.1046/j.1365-2958.2002.03146.x
Artur Schmidtchen40
Estimated H-index: 40
,
Inga-Maria Frick24
Estimated H-index: 24
(Lund University)
+ 2 AuthorsLars Björck60
Estimated H-index: 60
(Lund University)
Abstract
Summary Effectors of the innate immune system, the antibacterial peptides, have pivotal roles in preventing infection at epithelial surfaces. Here we show that proteinases of the significant human pathogens Pseudomonas aeruginosa , Enterococcus faecalis , Proteus mirabilis and Streptococcus pyogenes, degrade the antibacterial peptide LL-37. Analysis by mass spectrometry of fragments generated by P. aeruginosa elastase in vitro revealed that the initial cleavages occurred at Asn-Leu and Asp-Phe, followed by two breaks at Arg-Ile, thus inactivating the peptide. Proteinases of the other pathogens also degraded LL37 as determined by SDS-PAGE. Ex vivo , P. aeruginosa elastase induced LL-37 degradation in human wound fluid, leading to enhanced bacterial survival. The degradation was blocked by the metalloproteinase inhibitors GM6001 and 1, 10-phenantroline (both of which inhibited P. aeruginosa elastase, P. mirabilis proteinase, and E. faecalis gelatinase), or the inhibitor E64 (which inhibited S. pyogenes cysteine proteinase). Additional experiments demonstrated that dermatan sulphate and disaccharides of the structure [D UA(2S)-GalNAc(4,6S)], or sucroseoctasulphate, inhibited the degradation of LL-37. The results indicate that proteolytic degradation of LL-37 is a common virulence mechanism and that molecules which block this degradation could have therapeutic potential.
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Morihara K1
Estimated H-index: 1
,
Tsuzuki H1
Estimated H-index: 1
+ 2 AuthorsEbata M1
Estimated H-index: 1
183 Citations
Summary Production of erythrogenic toxin type B by Streptococcus pyogenes strain T19 was found to be strongly dependent on the pH of the cultivation medium. Maximum yields (> 100 mg of toxin/1) were obtained at pH 6. 0. In contrast no toxin production was serologically detectable at pH values above 6.5. Purified B-toxin was shown to consist of two components when assayed by SDS-electrophoresis. The molecular weight of the two components was estimated to be 30000 and 12000. Isoelectric focusing r...
70 Citations Source Cite
Published on Nov 16, 2001
Margareta Frohm Nilsson1
Estimated H-index: 1
2 Citations
Published on May 1, 2001in Nature 41.58
Pyong Woo Park33
Estimated H-index: 33
(Baylor College of Medicine),
Gerald B. Pier72
Estimated H-index: 72
(Brigham and Women's Hospital)
+ 1 AuthorsMerton Bernfield62
Estimated H-index: 62
(Boston Children's Hospital)
Cell-surface heparan sulphate proteoglycans (HSPGs) are ubiquitous and abundant receptors/co-receptors of extracellular ligands 1,2 , including many microbes 3-10 . Their role in microbial infections is poorly defined, however, because no cell-surface HSPG has been clearly connected to the pathogenesis of a particular microbe. We have previously shown that Pseudomonas aeruginosa, through its virulence factor LasA, enhances the in vitro shedding of syndecan-1-the predominant cell-surface HSPG of ...
178 Citations Source Cite
Published on Feb 1, 2001in Nature Medicine 32.62
Dilara Islam6
Estimated H-index: 6
,
Lisa Bandholtz6
Estimated H-index: 6
(Karolinska Institutet)
+ 4 AuthorsGudmundur H. Gudmundsson38
Estimated H-index: 38
(Karolinska Institutet)
Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator
349 Citations Source Cite
Published on Oct 1, 1991in Annals of Surgery 9.20
Judah Folkman151
Estimated H-index: 151
(Harvard University),
Sandor Szabo38
Estimated H-index: 38
(Harvard University)
+ 3 AuthorsYuen Shing23
Estimated H-index: 23
(Harvard University)
The complete purification of the first angiogenic molecule, basic fibroblast growth factor (bFGF), was carried out in the authors' laboratory in 1983. Application of this peptide to chronic wounds enhances angiogenesis and accelerates wound healing. The authors showed that an acid-stable form of bFGF (i.e., bFGF-CS23) could be administered orally to rats with duodenal ulcers. The peptide promoted a ninefold increase of angiogenesis in the ulcer bed and accelerated ulcer healing more potently tha...
238 Citations Source Cite
Published on Dec 1, 1990in Infection and Immunity 3.26
Kenji Okuda47
Estimated H-index: 47
,
K Morihara1
Estimated H-index: 1
+ 5 AuthorsJun Fukushima27
Estimated H-index: 27
The DNA-encoding alkaline proteinase (AP) of Pseudomonas aeruginosa IFO 3455 was cloned, and its complete nucleotide sequence was determined. When the cloned gene was ligated to pUC18, the Escherichia coli expression vector, the gene-incorporated bacteria expressed high levels of both AP activity and AP antigens. The amino acid sequence deduced from the nucleotide sequence revealed that the mature AP consists of 467 amino acids with a relative molecular weight of 49,507. The amino acid compositi...
42 Citations
Published on Mar 1, 1989in Journal of Bacteriology 3.22
Jun Fukushima27
Estimated H-index: 27
(Yokohama City University),
S Yamamoto2
Estimated H-index: 2
(Yokohama City University)
+ 4 AuthorsKenji Okuda47
Estimated H-index: 47
(Yokohama City University)
The DNA encoding the elastase of Pseudomonas aeruginosa IFO 3455 was cloned, and its complete nucleotide sequence was determined. When the cloned gene was ligated to pUC18, the Escherichia coli expression vector, bacteria carrying the gene exhibited high levels of both elastase activity and elastase antigens. The amino acid sequence, deduced from the nucleotide sequence, revealed that the mature elastase consisted of 301 amino acids with a relative molecular mass of 32,926 daltons. The amino aci...
58 Citations Source Cite
Published on Nov 1, 2000in Blood 15.13
Birgitta Agerberth46
Estimated H-index: 46
,
Jehad Charo21
Estimated H-index: 21
+ 7 AuthorsGudmundur H. Gudmundsson38
Estimated H-index: 38
We identified antibacterial components in human T and natural killer (NK) cells by using freshly isolated lymphocytes enriched for T and NK cells as starting material. After growing these lymphocytes for 5 days in the presence of interleukin (IL)–2, we isolated and characterized several antibacterial peptides/proteins from the supernatant—α-defensins (HNP 1-3), LL-37, lysozyme, and a fragment of histone H2B—although other active components were also present. We then used reverse transcriptase–po...
608 Citations
Published on Mar 1, 1997in Microbiology and Molecular Biology Reviews 13.44
A Rózalski1
Estimated H-index: 1
,
Z Sidorczyk1
Estimated H-index: 1
,
K Kotełko1
Estimated H-index: 1
The object of this review is the genus Proteus, which contains bacteria considered now to belong to the opportunistic pathogens. Widely distributed in nature (in soil, water, and sewage), Proteus species play a significant ecological role. When present in the niches of higher macroorganisms, these species are able to evoke pathological events in different regions of the human body. The invaders (Proteus mirabilis, P. vulgaris, and P. penneri) have numerous factors including fimbriae, flagella, o...
231 Citations
Cited By288
Published on Jan 1, 2009
Enterococci are gram-positive bacteria typically found as commensals in the gastro-intestinal tracts of most mammals. Enterococci, most notably Enterococcus faecalis and Enterococcus faecium, have become problematic causative agents of several nosocomially acquired infections including urinary tract infections, bacteremia, surgical sight infections, and endocarditis. These bacteria must first overcome the innate immune response in order to establish infection. Many bacteria produce capsular poly...
Published on Jan 1, 2009
Emma Andersson Nordahl1
Estimated H-index: 1
Antimicrobial peptides serve as a first line of defence against invading microorganisms and are an essential part of our fast innate immune system. They are ancient molecules found in all classes of life. Antimicrobial peptides rapidly kill a broad spectrum of microbes and are immunomodulatory, i.e. having additional actions influencing inflammation and other innate immune responses. Results presented in this thesis demonstrate that proteases of common human pathogens degrade and inactivate the ...
1 Citations
Published on Jan 1, 2013
Maira Goytia4
Estimated H-index: 4
(Emory University),
Justin L. Kandler5
Estimated H-index: 5
(Emory University),
William M. Shafer39
Estimated H-index: 39
(Emory University)
Cationic antimicrobial peptides (CAMPs) are essential compounds of the innate immunity system possessed by humans. CAMPs protect the host by exerting bactericidal activity, molecular signaling, modulating the immune response, and facilitating the communication between innate and acquired immunity. Over the millennia, bacteria have developed mechanisms to circumvent the antimicrobial activity of CAMPs, thereby promoting their survival during infection. In this chapter, we focus on the mechanisms ...
4 Citations Source Cite
Published on Sep 1, 2005in Hautarzt 0.66
A. Körber17
Estimated H-index: 17
,
Stephan Grabbe44
Estimated H-index: 44
,
Joachim Dissemond25
Estimated H-index: 25
Human antimicrobial peptides play a substantial role in the immune response to various dermatological diseases, such as acne, atopic dermatitis and psoriasis vulgaris, and even mucosal HIV-protection is mediated inter alia by antimicrobial peptides. In wound healing, the antimicrobial and immune-modulating properties of, in particular, human defensins and cathelicidins can affect important controlling factors. For example, the interaction between different antimicrobial peptides and growth facto...
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Published on Jan 1, 2006in Current Topics in Microbiology and Immunology 5.83
Birgitta Agerberth46
Estimated H-index: 46
(Karolinska Institutet),
Gudmundur H. Gudmundsson38
Estimated H-index: 38
(University of Iceland)
Antimicrobial peptides or host defence peptides are endogenous peptide antibiotics, which have been confirmed as an essential part of the immune system. Apart from direct killing of bacteria, a role for the peptides in antiviral and immunomodulatory functions has recently been claimed. In this chapter we have focused on the host contact with microbes, where these host defence peptides are key players. The interplay with commensals and pathogens in relation to antimicrobial peptide expression is ...
54 Citations Source Cite
Published on Jan 1, 2010
Jason Kindrachuk24
Estimated H-index: 24
(University of British Columbia),
Anastasia Nijnik20
Estimated H-index: 20
(University of British Columbia),
Robert E. W. Hancock119
Estimated H-index: 119
(University of British Columbia)
Host defense peptides are ubiquitous in nature and have been identified in every species for which they have been investigated. Although widely distributed, host defense peptides are characterized by a limited number of physical attributes, namely, small size and high percentages of cationic and hydrophobic residues. Additionally, host defense peptides are categorized into a few distinct structural classes: α-helical, β-sheet, extended, or loop structures. These diverse biomolecules represent an...
3 Citations Source Cite
Published on Jan 1, 2015
Ravindra Pal Singh11
Estimated H-index: 11
(Kyushu University),
Jiro Nakayama35
Estimated H-index: 35
(Kyushu University)
Enterococcus is a genus of Gram-positive bacteria that is ubiquitous in natural ecosystems, plants, and animals. Some species of Enterococcus are present in the normal gastrointestinal bacterial community. However, others notably Enterococcus faecalis and Enterococcus faecium often cause opportunistic infections such as bacteremia, endocarditis, urinary tract infections, posttreatment endodontic infections, and endophthalmitis (Arias et al. 2010). Bacteria often use quorum sensing (QS) systems t...
1 Citations Source Cite
Published on Jan 1, 2011
Anna Henningham16
Estimated H-index: 16
(University of Wollongong)
Published on Jan 1, 2015
Julia R. Dorin37
Estimated H-index: 37
(University of Edinburgh),
Brian McHugh9
Estimated H-index: 9
(University of Edinburgh)
+ 1 AuthorsDonald J. Davidson30
Estimated H-index: 30
(University of Edinburgh)
Antimicrobial peptides (also known as host defence peptides) are an increasingly well-characterized, central component of host defence against infection. These peptides are an ancient form of innate immunity, conserved across evolution; found in animals, plants and even produced by microorganisms themselves. As antibiotic resistance becomes an ever-greater concern for our ability to treat infectious diseases, the study of antimicrobial peptides is providing new insights into the functioning of i...
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