Role of Charge Properties of Bacterial Envelope in Bactericidal Action of Human Group IIA Phospholipase A2against Staphylococcus aureus

Koprivnjak, Tomaž; Peschel, Andreas; Gelb, Michael H.; Liang, Ning; Weiss, Jerrold

doi:10.1074/jbc.m205104200

Cited by 120 publications

(157 citation statements)

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“…In marked contrast, human group IIA sPLA 2 shows a dramatic dependence on the presence of Ͼ10 -20% anionic phosphatidylserine for binding to vesicles (10,20,21), which is consistent with its well established function as a Gram-positive bactericidal agent (22)(23)(24). Gram-positive membranes are highly rich in acidic phospholipids, especially phosphatidylglycerol, and the high density of basic residues (lysines and arginines) on the surface of the group IIA enzyme is important for allowing this enzyme to penetrate the highly anionic cell wall of Gram-positive bacteria (25,26).…”

Section: Discussionmentioning

confidence: 76%

Interfacial Enzymology of Parvovirus Phospholipases A2

Canaan

Zádori

Ghomashchi

et al. 2004

Journal of Biological Chemistry

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105

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The capsid of parvoviruses proteins were recently shown to contain secreted phospholipase A 2 (sPLA 2 )-like activity that is required during host cell entry. Parvoviral PLA 2 domains have little sequence identity with sPLA 2 s and lack disulfide bonds. In the present study, after bacterial expression and purification, the biochemical characterizations of these first PLA 2 s identified in viruses have been investigated, and a comparison has been made with other known PLA 2 s. The specific activities of three viral PLA 2 s differed by 3 orders of magnitude, with porcine parvovirus PLA 2 displaying a specific activity similar to that of the most active sPLA 2 s (e.g. human group IIA) and the human AAV2 and B19 parvoviral enzymes displaying approximately 10 3 lower specific activities (similar to human sPLA 2 groups IIE and XIIA). These differences were not caused by weaker Ca 2؉ or interfacial binding. The specific activities of the viral PLA 2 s on zwitterionic or anionic phospholipid vesicles were comparable. The viral PLA 2 s did not display a preference for unsaturated versus saturated sn-2 fatty acyl chains and hydrolyzed all major classes of glycerophospholipids except phosphatidylinositol. Incubation of mammalian cells with porcine parvovirus PLA 2 led to the release of arachidonic acid into the culture medium. Interestingly, among nine previously known sPLA 2 inhibitors, only a subset showed inhibition of the viral PLA 2 s and with weak potency, indicating that the active sites of these new enzymes are structurally distinct from those of sPLA 2 s. Based on these distinct enzymatic and structural properties, we propose to classify the parvovirus PLA 2 s within the PLA 2 superfamily as group XIII enzymes.Parvoviruses are a family of small DNA viruses comprising two subfamilies, the Parvovirinae that infect vertebrates, including man, and the Densovirinae that infect invertebrates such as insect and shrimp species. These viruses depend, because of their limited genome content, on enzymes and precursors present during the S phase of the cell for their replicative functions and thus show a proclivity for actively dividing cells. Consequently, many parvoviruses, such as the porcine parvovirus (1) (PPV) 1 and the human B19 (2) parvovirus, are fetotropic, resulting in abortions, or have a predisposition to infect other mitosis-active tissues such as transformed cells ("oncolytic property") (3).These nonenveloped, icosahedral viruses have a diameter of approximately 25 nm and contain a linear, single-stranded DNA genome of approximately 4 -6 kb. The structure of several parvovirus capsids has been solved to nearly atomic resolution, whereas the DNA is only partly ordered (4, 5). The capsid is composed of 60 structurally equivalent protein subunits, each containing a ␤-barrel jelly roll in which some loops between the ␤-strands intertwine with loops from neighboring subunits and cover the viral surface for specific functions such as recognition of cellular receptors. Approximately 10 out of the 60 capsid proteins ha...

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Section: Discussionmentioning

confidence: 76%

Interfacial Enzymology of Parvovirus Phospholipases A2

Canaan

Zádori

Ghomashchi

et al. 2004

Journal of Biological Chemistry

Self Cite

105

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“…The absence of dlt in S. aureus results in a high susceptibility to being killed by neutrophils and also reduces the ability to colonize plastic or glass surfaces, a factor in catheterassociated infection (Collins et al, 2002;Gross et al, 2001). In addition, it has been found that a dlt mutant is highly susceptible to human phospholipase A 2 , a cationic protein that exhibits antibacterial activity against S. aureus, owing to a strong surface negative charge (Koprivnjak et al, 2002). Furthermore, dlt in group A streptococci has been found to promote survival in neutrophils and invasion of epithelial cells (Kristian et al, 2005), and dlt in Streptococcus agalactiae and Listeria monocytogenes is associated with susceptibility to phagocytic cells (Abachin et al, 2002;Poyart et al, 2003).…”

Section: Discussionmentioning

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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“…We have previously clarified that lysozyme, sPLA2, -defensin1 and β-defensin2 are secreted mainly from exocrine glands associated with the upper alimentary tract, but only lysozyme and sPLA2 are also secreted from the Paneth cells in the small intestine [29]. Lysozyme mainly acts against Gram-positive bacteria, and several Gram-negative bacteria [1,12], as well as sPLA2 [13,16]. α-defensins and β-defensins act for both Gram-positive and Gram-negative bacteria [4,6,15].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and Histoplanimetrical Study on the Spatial Relationship between the Settlement of Indigenous Bacteria and the Secretion of Bactericidal Peptides in Rat Alimentary Tract

Yokoo

Miyata

Udayanga

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. To clarify the regulatory mechanism by bactericidal peptides secretion, the secretion of bactericidal peptides was immunohistochemically and histoplanimetrically compared with the degree of Gram-positive/negative bacterial colonization throughout the rat alimentary tract. In the associated exocrine glands from the oral cavity to the stomach, no comparable differences were observed under the changes of development of indigenous bacterial colonies. In the small intestine, immunopositive granules for lysozyme and secretory phospholipase A2 (sPLA2) were markedly decreased, whereas immunopositive vacuoles in the Paneth cells were more increased at sites with hyper-development of indigenous bacterial colonies in the intervillous spaces than at sites with no or less development. No changes in exocrine glands were observed in the large intestine because of the constant existence of large quantities of bacteria. Gram-positive bacterial colonies on the mucosal surfaces were dominant from the oral cavity to the stomach. Gram-negative bacteria were dominant in the large intestine, and the distributions of both Gram-positive and negative bacteria were intermediate in the small intestine. These findings suggest that lysozyme and sPLA2 secreted from the Paneth cells contribute to the regulation of the proliferation of indigenous bacteria in the intervillous spaces of the small intestine, and that the inversion of distributions of Grampositive and -negative bacteria in the alimentary tract might be caused by the secretion of lysozyme and sPLA2 in the small intestine.KEY WORDS: alimentary tract, bactericidal peptides, digestive organs, indigenous bacteria, Paneth cells.

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Role of Charge Properties of Bacterial Envelope in Bactericidal Action of Human Group IIA Phospholipase A2against Staphylococcus aureus

Cited by 120 publications

References 50 publications

Interfacial Enzymology of Parvovirus Phospholipases A2

Interfacial Enzymology of Parvovirus Phospholipases A2

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

Immunohistochemical and Histoplanimetrical Study on the Spatial Relationship between the Settlement of Indigenous Bacteria and the Secretion of Bactericidal Peptides in Rat Alimentary Tract

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