In vivo and in vitro antibacterial activity of acanthospermal B, a sesquiterpene lactone isolated from Acanthospermum hispidum.

PHYTOTHERAPY RESEARCH

JOHN WILEY & SONS LTD

Año: 2010

0951-418X

m: phytotherapy.research@wiley.co.uk To: arename@fbqf.unt.edu.ar, marioarena@yahoo.com CC: Subject: PTR-09-1028.R3 - Decision Body: 5 August 2010 Dear Dr Arena, It is a pleasure to accept your manuscript entitled "In vivo and in vitro antibacterial activity of acanthospermal B, a sesquiterpene lactone isolated from Acanthospermum hispidum." in its current form for publication in Phytotherapy Research. A signed copyright transfer agreement is needed for publication. If you have not already provided us with one you can access the copyright transfer agreement at: http://media.wiley.com/assets/1540/86/ctaaglobal.pdf To enable the publisher to disseminate the author´s work to the fullest extent, the author must sign a Copyright Transfer Agreement, transferring the copyright of the article from the author to the publisher. If you have not yet uploaded a CTA, please ensure that you have identified the form with the manuscript ID number; scan your signed CTA and e-mail to ptrproofs@wiley.com stating the manuscript ID number in the subject line of the e-mail. Please note that this does not take away your rights to reuse your own article after publication, and that if the copyright belongs to your employing institution, they should sign the form instead of you. If you have already provided us with the signed form, you do not need to do anything at this stage. You will be contacted by our typesetters/copyeditors shortly. Thank you for your contribution. Sincerely, Rachael Bilginer Managing Editor Phytotherapy Research phytotherapy.research@wiley.co.uk  Acanthospermal B (AcB), the major sesquiterpene lactone (SL) of Acanthospermumhispidum, an herb widely spread in Argentina, is a selective antibacterial agent againstEnterococcus faecalis and Staphylococcus aureus, but inactive on Gram negative andLactobacillus. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main microorganisms involved in human chronic infection. A balbc mice skin infection model was developed to reproduce the lesions caused by acute and chronic infections produced by  MRSA. After determination of the maximum concentration of AcB unable to produce tissular injury after intradermal injection, the anti MRSA effect of AcB was evaluated on  skin, liver and spleen tissues of infected mice. AcB, at doses of 2.5 mg/kg, produced a ten times decrease of MRSA growth in skin infection. In addition, the same dose prevented the dissemination to liver and/or spleen. AcB also displayed a bacteriostatic effect, in vitro, onMRSA cultures at 50 μg/mL that seems to be caused by partial denaturation of totalbacterial DNA and/or inhibition of the PCR reaction in not denaturized DNA. Finally, total  MRSA cell wall lysis occurred at a concentration of 100 μg/mL of AcB after 2 h of exposure.