Inhibition of intracellular macromolecular synthesis in Staphylococcus aureus by thrombin-induced platelet microbicidal proteins.
Thrombin-induced platelet microbicidal proteins (tPMP-1 and tPMP-2) are believed to initiate their staphylocidal effects via cytoplasmic membrane perturbation. The aim of the present study was to investigate the role of subsequent inhibition of macromolecular synthesis in the staphylocidal mechanisms of tPMP-1 and tPMP-2 in an isogenic tPMP-susceptible and -resistant strain pair (ISP479C and ISP479R, respectively). In ISP479C, tPMP-1 and tPMP-2 (2 microg/mL) exerted significant bactericidal effects and significantly reduced DNA and RNA synthesis (P <.05 vs. control). In contrast, tPMP-1 and tPMP-2 exerted reduced staphylocidal effects and significantly reduced inhibition of DNA and RNA synthesis against ISP479R, as compared with ISP479C (P <.05). However, tPMP-1 and tPMP-2 (2 microg/mL) caused equivalent degrees of inhibition of protein synthesis in both ISP479C and ISP479R. Collectively, these observations are consistent with the hypothesis that inhibition of specific macromolecular synthesis pathways is integral to the overall staphylocidal mechanism(s) of tPMPs.
Xiong
Yan-Qiong
YQ
Department of Medicine, Division of Infectious Diseases, St. John's Cardiovascular Research Center, Harbor-UCLA Research and Education Institute, Torrance, CA 90502, USA. Xiong@HUMC.edu
Bayer
Arnold S
AS
Yeaman
Michael R
MR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D001798:Blood Proteins / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D012329:RNA, Bacterial / Q000096:biosynthesis; D011817:Rabbits; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001798:Blood Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; C077150:platelet microbicidal protein, Oryctolagus cuniculus