Abstract
Strains of Staphylococcus aureus and coagulase-negative Staphylococcus with different antibiotic susceptibilities were selected to be the test targets of four synthesized compounds of N-aryl-4-guanidinomethylbenzoates and N-aryl-4-guanidinobenzamides. Minimum inhibitory concentrations of the four compounds showed comparable results to 13 commercial antibiotics. Metabolomics analysis based on GC–MS indicated that the four compounds shared the similar antimicrobial mechanism with clindamycin, but K–B disc diffusion tests implied that their exact binding site might be different from clindamycin or the current macrolide resistance mechanisms had no effect on the actions of synthesized compounds. The major effects of the studied compounds on the intercellular metabolites of S. aureus were the increased intracellular d-glucose, proline, phosphate and propanoic acid concentrations. This study proved metabolomics analysis was a promising tool in antibiotic mechanism research.




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Olofsson SK, Cars O (2007) Clin Infect Dis 45(2):129–136. doi:10.1086/519256
Yoneyama H, Katsumata R (2006) Biosci Biotechnol Biochem 70(5):1060–1075
Schmidt FR (2004) Appl Microbiol Biotechnol 63(4):335–343. doi:10.1007/s00253-003-1344-1
Freiberg C, Brunner N, Macko L, Fischer HP (2006) Mol Cell Proteomics 5(12):2326–2335. doi:10.1074/mcp.M600127-MCP200
Yu Y, Yi ZB, Liang YZ (2007) FEBS Lett 581(22):4179–4183. doi:10.1016/j.febslet.2007.07.056
Allen J, Davey HM, Broadhurst D, Rowland JJ, Oliver SG, Kell DB (2004) Appl Environ Microbiol 70(10):6157–6165. doi:10.1128/AEM.70.10.6157-6165.2004
Yu WY, Yang LX, Xie JS, Zhou L, Jiang XY, Zhu DX et al (2008) Acta Pharmacol Sin 29(2):267–277
Clinical and Laboratory Standards Institute (CLSI) (2008) Performance standards for antimicrobial disk susceptibility tests; approved standard, 10th edn. Wayne, USA
Clinical and Laboratory Standards Institute (CLSI) (2008) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Wayne, USA
Walsh C (2000) Nature 406(6797):775–781. doi:10.1038/35021219
Berdy J (1974) Adv Appl Microbiol 18:309–406
Wang J (2009) Mass Spectrom Rev 28(1):50–92. doi:10.1002/mas.20189
Jana S, Deb JK (2006) Appl Microbiol Biotechnol 70(2):140–150. doi:10.1007/s00253-005-0279-0
Fisher JF, Meroueh SO, Mobashery S (2005) Chem Rev 105(2):395–424. doi:10.1021/cr030102i
Domagala JM (1994) J Antimicrob Chemother 33(4):685–706
Clinical and Laboratory Standards Institute (CLSI) (2007) Performance standards for antimicrobial susceptibility testing; 17th informational supplement. Approved standard MS100–S17. Wayne, USA
Gao P, Shi C, Tian J, Shi X, Yuan K, Lu X et al (2007) J Pharm Biomed Anal 44(1):180–187. doi:10.1016/j.jpba.2007.02.015
Tian J, Shi C, Gao P, Yuan K, Yang D, Lu X et al (2008) J Chromatogr B Anal Technol Biomed Life Sci 871(2):220–226. doi:10.1016/j.jchromb.2008.06.031
Tian J, Sang P, Gao P, Fu R, Yang D, Zhang L et al (2009) J Sep Sci 32(13):2281–2288. doi:10.1002/jssc.200800727
Smith CA, Want EJ, O’Maille G, Abagyan R, Siuzdak G (2006) Anal Chem 78(3):779–787. doi:10.1021/ac051437y
Rabinowitz JD, Kimball E (2007) Anal Chem 79(16):6167–6173. doi:10.1021/ac070470c
Tusher VG, Tibshirani R, Chu G (2001) Proc Natl Acad Sci USA 98(9):5116–5121. doi:10.1073/pnas.091062498
Eady EA, Ross JI, Tipper JL, Walters CE, Cove JH, Noble WC (1993) J Antimicrob Chemother 31(2):211–217
Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H (1999) Antimicrob Agents Chemother 43(12):2823–2830
Dixon JM (1968) Can Med Assoc J 99(22):1093–1094
Barcs I (1985) Acta Microbiol Hung 32(3):241–248
Watanakunakorn C (1976) Am J Med 60(3):419–425
Drinkovic D, Fuller ER, Shore KP, Holland DJ, Ellis-Pegler R (2001) J Antimicrob Chemother 48(2):315–316
Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH (2003) J Clin Microbiol 41(10):4740–4744
Weisblum B, Demohn V (1969) J Bacteriol 98(2):447–452
Williams TD, Wu H, Santos EM, Ball J, Katsiadaki I, Brown MM et al (2009) Environ Sci Technol 43(16):6341–6348
Decad GM, Nikaido H (1976) J Bacteriol 128(1):325–336
Griffiths WJ, Karu K, Hornshaw M, Woffendin G, Wang Y (2007) Eur J Mass Spectrom 13(1):45–50. doi:10.1255/ejms.850
Chen C, Gonzalez FJ, Idle JR (2007) Drug Metab Rev 39(2–3):581–597. doi:10.1080/03602530701497804
Khoo SH, Al-Rubeai M (2007) Biotechnol Appl Biochem 47(2):71–84. doi:10.1042/BA20060221
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We would like to express our gratitude to the technologists in Dalian Center of Clinical Laboratory.
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Liu, Y., Wen, J., Wang, Y. et al. Postulating Modes of Action of Compounds with Antimicrobial Activities through Metabolomics Analysis. Chroma 71, 253–258 (2010). https://doi.org/10.1365/s10337-009-1447-7
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DOI: https://doi.org/10.1365/s10337-009-1447-7


