Document Detail


S-nitrosated α-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis.
MedLine Citation:
PMID:  23047897     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Treating infections with exogenous NO, which shows broad-spectrum antimicrobial activity, appears to be effective. Similar to NO biosynthesis, biosynthesis of α-1-acid glycoprotein variant A (AGPa), with a reduced cysteine (Cys149), increases markedly during inflammation and infection. We hypothesized that AGPa is an S-nitrosation target in acute-phase proteins. This study aimed to determine whether S-nitrosated AGPa (SNO-AGPa) may be the first compound of this novel antibacterial class against multidrug-resistant bacteria. AGPa was incubated with RAW264.7 cells activated by lipopolysaccharide and interferon-γ. The antimicrobial effects of SNO-AGPa were determined by measuring the turbidity of the bacterial suspensions in vitro and survival in a murine sepsis model in vivo, respectively. Results indicated that endogenous NO generated by activated RAW264.7 cells caused S-nitrosation of AGPa at Cys149. SNO-AGPa strongly inhibited growth of gram-positive, gram-negative, and multidrug-resistant bacteria and was an extremely potent bacteriostatic compound (IC(50): 10(-9) to 10(-6) M). The antibacterial mechanism of SNO-AGPa involves S-transnitrosation from SNO-AGPa to bacterial cells. Treatment with SNO-AGPa, but not with AGPa, markedly reduced bacterial counts in blood and liver in a mouse sepsis model. The sialyl residues of AGPa seem to suppress the antibacterial activity, since SNO-asialo AGPa was more potent than SNO-AGPa.-Watanabe, K., Ishima, Y., Akaike, T., Sawa, T., Kuroda, T., Ogawa, W., Watanabe, H., Suenaga, A., Kai, T., Otagiri, M., Maruyama, T. S-nitrosated α-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis.
Authors:
Kaori Watanabe; Yu Ishima; Takaaki Akaike; Tomohiro Sawa; Teruo Kuroda; Wakano Ogawa; Hiroshi Watanabe; Ayaka Suenaga; Toshiya Kai; Masaki Otagiri; Toru Maruyama
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-9
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  -     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Department of Biopharmaceutics and.
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