Degradation of Human Antimicrobial Peptide LL-37 by
            <i>Staphylococcus aureus</i>
            -Derived Proteinases

Sieprawska-Lupa, Magdalena; Mydel, Piotr; Krawczyk, K; Wójcik, Kinga; Puklo, Magdalena; Lupa, Boguslaw; Suder, Piotr; Silberring, Jerzy; Reed, Matthew S.; Pohl, Jan; Shafer, William M.; McAleese, Fionnuala; Foster, Timothy J.; Travis, J.; Potempa, Jan

doi:10.1128/aac.48.12.4673-4679.2004

Cited by 472 publications

(398 citation statements)

References 50 publications

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“…Because no gene immediately adjacent to the PSMs showed clear homology to known proteinases, we explored the potential contribution of the well studied zinc-dependent S. aureus metalloprotease aureolysin. Previous studies have shown that aureolysin is promiscuous in its enzymatic activity, with the ability to cleave its own extracellular cell wall proteins, the human-derived antimicrobial peptide LL-37, and several other substrates (30,31).…”

Section: Imaging Mass Spectrometry Of Ca-mrsa-mentioning

confidence: 99%

Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry

Gonzalez

Okumura

Hollands

et al. 2012

Journal of Biological Chemistry

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Background: Phenol-soluble modulins (PSMs) are small peptides of Staphylococcus aureus with immunosuppressive and antimicrobial properties. Results: Imaging mass spectrometry (IMS) identified PSM derivatives with properties different from those of the parent forms. Conclusion: S. aureus generates truncated PSMs with altered antimicrobial and immunostimulatory properties and aureolysin may contribute to processing of some PSMs. Significance: Observations using the technology of IMS expand our understanding of S. aureus PSMs.

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Section: Imaging Mass Spectrometry Of Ca-mrsa-mentioning

confidence: 99%

Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry

Gonzalez

Okumura

Hollands

et al. 2012

Journal of Biological Chemistry

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“…To date, in S. aureus, three types of mechanism that affect susceptibility to antimicrobial peptides have been identified. These are (1) trapping defensins by binding to staphylokinase (Braff et al, 2007;Jin et al, 2004), (2) digestion of peptides by proteinase (Sieprawska-Lupa et al, 2004), and (3) changing the bacterial cell surface charge via dlt and mprF (Li et al, 2007a;Peschel et al, 1999Peschel et al, , 2001. mprF was first identified as fmtC, which was shown to affect the meticillin-resistance level in MRSA (Komatsuzawa et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Growth-phase dependence of susceptibility to antimicrobial peptides in Staphylococcus aureus

et al. 2011

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Bacterial cell surface charge is responsible for susceptibility to cationic antimicrobial peptides. Previously, Staphylococcus aureus dlt and mprF were identified as factors conferring a positive charge upon cell surfaces. In this study, we investigated the regulation of cell surface charge during growth. Using a group of S. aureus MW2 mutants, which are gene-inactivated in 15 types of two-component systems (TCSs), we tested dltC and mprF expression and found that two TCSs, aps and agr, were associated with dltC and mprF expression in a growth phase-dependent manner. The first of these, aps, which had already been identified as a sensor of antimicrobial peptides and a positive regulator of dlt and mprF expression, was expressed strongly in the exponential phase, while its expression was significantly suppressed by agr in the stationary phase, resulting in higher expression of dltC and mprF in the exponential phase and lower expression in the stationary phase. Since both types of expression affected the cell surface charge, the susceptibility to antimicrobial peptides and cationic antibiotics was changed during growth. Furthermore, we found that the ability to sense antimicrobial peptides only functioned in the exponential phase. These results suggest that cell surface charge is tightly regulated during growth in S. aureus. INTRODUCTIONStaphylococcus aureus is a well-known major pathogen in humans. S. aureus produces many toxins and exoenzymes to cause various suppurative diseases, food poisoning and toxic shock syndrome (Foster, 2004;Lowy, 1998;Manders, 1998). Furthermore, strains isolated clinically, especially meticillin-resistant S. aureus (MRSA), exhibit multiple antibiotic resistance (Deurenberg et al., 2007;Grundmann et al., 2006), resulting in serious problems with regard to therapy of S. aureus infectious disease. Recently, besides these virulence factors, S. aureus has also been found to possess the ability to produce several factors that protect against host-derived innate immune factors, such as complement, antibodies and neutrophils, as well as recently recognized innate immune antimicrobial peptides, such as LL-37 and defensins (Foster, 2005;Rooijakkers et al., 2005).Human antimicrobial peptides are one of the innate immune factors and are produced in various tissues and organs, such as the skin, lung and intestines (Ganz et al., 1985;Ganz & Lehrer, 1995;Lehrer & Ganz, 1999;Selsted & Ouellette, 2005;Zaiou & Gallo, 2002). The most wellknown antimicrobial peptides are the defensins. Defensins are classified into two types: alpha-defensins from neutrophils and Paneth cells, and beta-defensins from epithelial cells (Cunliffe, 2003;Ganz et al., 1985;Ganz & Lehrer, 1995). Another major peptide is CAP18/LL37, which is found in neutrophils and epithelial cells (Larrick et al., 1995;Ramanathan et al., 2002;Zaiou & Gallo, 2002). These cationic peptides are electrostatically attracted to bacterial cell surfaces. Then, the peptides interact with membrane lipids, causing membrane permeabilization and leading to ...

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“…SA positive for QuacA may exhibit higher levels of resistance to a cationic AMPs, as demonstrated experimentally for the platelet-derived AMP, tPMP [33]. The metalloprotease aureolysin is released by SA and can degrade human cathelicidin LL-37 in a dose and timedependent manner [34]; strains producing lower levels of aureolysin were found to be more susceptible to cathelidicin killing. A proteolytic activty released by SA also inactivates lactoferricin B, a cationic AMP derived from the N-terminus of mammalian lactoferrin [35].…”

Section: Infections Due To Microbial Resistance To the Innate Immunementioning

confidence: 98%

Innate barriers against skin infection and associated disorders

Gallo

Nizet

2008

Drug Discovery Today: Disease Mechanisms

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The innate immune system is primarily responsible for prevention of infection of the skin by pathogens, but is also important in control of inflammation. The components of innate immunity are frequently misunderstood based on a historical bias for leukocyte-mediated immune defense. Many participating cell types are often overlooked, in particular epithelial cells that provide an early and critical step to innate immune defense. This review will discuss our epithelial barrier to infection with emphasis on how microbes subvert this system, and human diseases associated with these events.

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Degradation of Human Antimicrobial Peptide LL-37 by Staphylococcus aureus -Derived Proteinases

Cited by 472 publications

References 50 publications

Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry

Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry

Growth-phase dependence of susceptibility to antimicrobial peptides in Staphylococcus aureus

Innate barriers against skin infection and associated disorders

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