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The antibacterial properties of secreted phospholipases A(2) - A major physiological role for the group IIA enzyme that depends on the very high pI of the enzyme to allow penetration of the bacterial cell wall

The antibacterial properties of secreted phospholipases A(2) - A major physiological role for the group IIA enzyme that depends on the very high pI of the enzyme to allow penetration of the bacterial cell wall
The antibacterial properties of secreted phospholipases A(2) - A major physiological role for the group IIA enzyme that depends on the very high pI of the enzyme to allow penetration of the bacterial cell wall
The antibacterial properties of human group IIA secreted phospholipase A(2) against Gram-positive bacteria as a result of membrane hydrolysis have been reported. Using Micrococcus luteus as a model system, we demonstrate the very high specificity of this human enzyme for such hydrolysis compared with the group IB, IIE, lIF, V, and X human secreted phospholipase A(2)s. A unique feature of the group IIA enzyme is its very high pI due to a large excess of cationic residues on the enzyme surface. The importance of this global positive charge in bacterial cell membrane hydrolysis and bacterial killing has been examined using charge reversal mutagenesis. The global positive charge on the enzyme surface allows penetration through the bacterial cell wall, thus allowing access of this enzyme to the cell membrane. Reduced bacterial killing was associated with the loss of positive charge and reduced cell membrane hydrolysis. All mutants were highly effective in hydrolyzing the bacterial membrane of cells in which the cell wall was permeabilized with lysozyme. These same overall characteristics were also seen with suspensions of Staphylococcus aureus and Listeria innocua, where cell membrane hydrolysis and antibacterial activity of human group IIA enzyme was also lost as a result of charge reversal mutagenesis.
0021-9258
1788-1793
Beers, S.A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Buckland, A.G.
378d0e1a-8bde-4754-9d1a-dd3cf1eb8207
Koduri, R.S.
620eb50f-fb93-472c-947a-103f2a1eea93
Cho, W.
6355b8cf-38b0-4c08-8386-1856f620a7e6
Gelb, M.H.
be15b679-9672-486f-8d02-3eb65da4dad2
Wilton, D.C.
4b995f66-ad6c-4d96-9179-c64f3b54466a
Beers, S.A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Buckland, A.G.
378d0e1a-8bde-4754-9d1a-dd3cf1eb8207
Koduri, R.S.
620eb50f-fb93-472c-947a-103f2a1eea93
Cho, W.
6355b8cf-38b0-4c08-8386-1856f620a7e6
Gelb, M.H.
be15b679-9672-486f-8d02-3eb65da4dad2
Wilton, D.C.
4b995f66-ad6c-4d96-9179-c64f3b54466a

Beers, S.A., Buckland, A.G., Koduri, R.S., Cho, W., Gelb, M.H. and Wilton, D.C. (2001) The antibacterial properties of secreted phospholipases A(2) - A major physiological role for the group IIA enzyme that depends on the very high pI of the enzyme to allow penetration of the bacterial cell wall. The Journal of Biological Chemistry, 277 (3), 1788-1793. (doi:10.1074/jbc.M109777200).

Record type: Article

Abstract

The antibacterial properties of human group IIA secreted phospholipase A(2) against Gram-positive bacteria as a result of membrane hydrolysis have been reported. Using Micrococcus luteus as a model system, we demonstrate the very high specificity of this human enzyme for such hydrolysis compared with the group IB, IIE, lIF, V, and X human secreted phospholipase A(2)s. A unique feature of the group IIA enzyme is its very high pI due to a large excess of cationic residues on the enzyme surface. The importance of this global positive charge in bacterial cell membrane hydrolysis and bacterial killing has been examined using charge reversal mutagenesis. The global positive charge on the enzyme surface allows penetration through the bacterial cell wall, thus allowing access of this enzyme to the cell membrane. Reduced bacterial killing was associated with the loss of positive charge and reduced cell membrane hydrolysis. All mutants were highly effective in hydrolyzing the bacterial membrane of cells in which the cell wall was permeabilized with lysozyme. These same overall characteristics were also seen with suspensions of Staphylococcus aureus and Listeria innocua, where cell membrane hydrolysis and antibacterial activity of human group IIA enzyme was also lost as a result of charge reversal mutagenesis.

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Submitted date: 10 October 2001
Published date: 12 November 2001

Identifiers

Local EPrints ID: 35566
URI: http://eprints.soton.ac.uk/id/eprint/35566
ISSN: 0021-9258
PURE UUID: 40ec1bd7-0ef9-4293-a700-8fd495a37d28
ORCID for S.A. Beers: ORCID iD orcid.org/0000-0002-3765-3342

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Date deposited: 19 May 2006
Last modified: 09 Jan 2022 03:05

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Contributors

Author: S.A. Beers ORCID iD
Author: A.G. Buckland
Author: R.S. Koduri
Author: W. Cho
Author: M.H. Gelb
Author: D.C. Wilton

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