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PMID: 10816510 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity.

Infection and immunity ·Vol. 68 ·No. 6 ·2000-06-00 ·Pages 3548-53

Bayer AS, Prasad R, Chandra J, Koul A, Smriti M, Varma A, Skurray RA, Firth N, Brown MH, Koo SP, Yeaman MR

Abstract

Platelet microbicidal proteins (PMPs) are small, cationic peptides which possess potent microbicidal activities against common bloodstream pathogens, such as Staphylococcus aureus. We previously showed that S. aureus strains exhibiting resistance to thrombin-induced PMP (tPMP-1) in vitro have an enhanced capacity to cause human and experimental endocarditis (T. Wu, M. R. Yeaman, and A. S. Bayer, Antimicrob. Agents Chemother. 38:729-732, 1994; A. S. Bayer et al., Antimicrob. Agents Chemother. 42:3169-3172, 1998; V. K. Dhawan et al., Infect. Immun. 65:3293-3299, 1997). However, the mechanisms mediating tPMP-1 resistance in S. aureus are not fully delineated. The S. aureus cell membrane appears to be a principal target for the action of tPMP-1. To gain insight into the basis of tPMP-1 resistance, we compared several parameters of membrane structure and function in three tPMP-1-resistant (tPMP-1(r)) strains and their genetically related, tPMP-1-susceptible (tPMP-1(s)) counterpart strains. The tPMP-1(r) strains were derived by three distinct methods: transposon mutagenesis, serial passage in the presence of tPMP-1 in vitro, or carriage of a naturally occurring multiresistance plasmid (pSK1). All tPMP-1(r) strains were found to possess elevated levels of longer-chain, unsaturated membrane lipids, in comparison to their tPMP-1(s) counterparts. This was reflected in corresponding differences in cell membrane fluidity in the strain pairs, with tPMP-1(r) strains exhibiting significantly higher degrees of fluidity as assessed by fluorescence polarization. These data provide further support for the concept that specific alterations in the cytoplasmic membrane of S. aureus strains are associated with tPMP-1 resistance in vitro.

MeSH Terms
Amino Acids/metabolism Anti-Bacterial Agents/pharmacology Biological Transport Blood Proteins/pharmacology Cell Membrane/chemistry,drug effects Chemokines DNA Transposable Elements Drug Resistance, Microbial Fatty Acids/analysis Membrane Fluidity/drug effects Mutagenesis, Insertional Phenotype Phospholipids/analysis Species Specificity Staphylococcus aureus/drug effects,genetics beta-Thromboglobulin
Chemicals
Amino Acids Anti-Bacterial Agents Blood Proteins Chemokines DNA Transposable Elements Fatty Acids PPBP protein, human Phospholipids beta-Thromboglobulin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Bayer A S
Research and Education Institute, St. John's Cardiovascular Research Center and the Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, 90509, USA. Bayer@humc.edu
Prasad R
Chandra J
Koul A
Smriti M
Varma A
Skurray R A
Firth N
Brown M H
Koo S P
Yeaman M R
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.68.6.3548-3553.2000
Email
bayer@humc.edu
Published
2000-06-00
Pages
3548-53
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC97641
Subset
IM
Grants
NIAID NIH HHS · R01 AI039001 · United States
NIAID NIH HHS · R01 AI039108 · United States
NIAID NIH HHS · AI39108 · United States
NIAID NIH HHS · AI39001 · United States
NIAID NIH HHS · R29 AI039001 · United States
External Links
PubMed source DOI: 10.1128/IAI.68.6.3548-3553.2000 PMC Full Text View journal details
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