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Compounds restore antibiotics' efficacy against MRSA

Date:
March 9, 2016
Source:
American Association for the Advancement of Science
Summary:
Antibiotics rendered useless by the notorious methicillin-resistant Staphylococcus aureus, (MRSA) may get a second life, thanks to compounds that can restore the bug's susceptibility to antibiotics, according to a new study in mice.
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Antibiotics rendered useless by the notorious methicillin-resistant Staphylococcus aureus, (MRSA) may get a second life, thanks to compounds that can restore the bug's susceptibility to antibiotics, according to a new study in mice. The compounds have no antimicrobial activity on their own, but become lethal when combined with existing antibiotics, offering a potential combination strategy against MRSA.

MRSA poses a major public health crisis worldwide and is the second leading cause of death from drug-resistant bacterial infections in the U.S. The bacteria have grown resistant to the entire class of β-lactam antibiotics, which includes penicillin and methicillin, creating an urgent need to develop new drugs or, alternatively, boost the efficacy of existing ones.

Here, Sang Ho Lee and colleagues conducted a drug screen for inhibitors of wall teichoic acid, a major structural component of the bacterial cell wall that is thought to buffer MRSA against the antimicrobial effects of β-lactams. The researchers identified two synthetic compounds, which they named tarocin A and tarocin B, that block an enzyme that kickstarts wall teichoic acid production.

In culture, the compounds on their own had no effect on MRSA growth, but when paired with β-lactams, killed various clinical strains of MRSA. Whereas mice succumbed to MRSA infection when treated with either tarocin or β-lactam alone, animals treated with both drugs showed markedly reduced infection and improved survival.

The researchers say that with further development, tarocins may offer a new class of adjuvants for reviving β-lactam antibiotics' efficacy against MRSA.


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Materials provided by American Association for the Advancement of Science. Note: Content may be edited for style and length.


Journal Reference:

  1. S. H. Lee, H. Wang, M. Labroli, S. Koseoglu, P. Zuck, T. Mayhood, C. Gill, P. Mann, X. Sher, S. Ha, S.-W. Yang, M. Mandal, C. Yang, L. Liang, Z. Tan, P. Tawa, Y. Hou, R. Kuvelkar, K. DeVito, X. Wen, J. Xiao, M. Batchlett, C. J. Balibar, J. Liu, J. Xiao, N. Murgolo, C. G. Garlisi, P. R. Sheth, A. Flattery, J. Su, C. Tan, T. Roemer. TarO-specific inhibitors of wall teichoic acid biosynthesis restore  -lactam efficacy against methicillin-resistant staphylococci. Science Translational Medicine, 2016; 8 (329): 329ra32 DOI: 10.1126/scitranslmed.aad7364

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American Association for the Advancement of Science. "Compounds restore antibiotics' efficacy against MRSA." ScienceDaily. ScienceDaily, 9 March 2016. <www.sciencedaily.com/releases/2016/03/160309151838.htm>.
American Association for the Advancement of Science. (2016, March 9). Compounds restore antibiotics' efficacy against MRSA. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/03/160309151838.htm
American Association for the Advancement of Science. "Compounds restore antibiotics' efficacy against MRSA." ScienceDaily. www.sciencedaily.com/releases/2016/03/160309151838.htm (accessed May 23, 2017).

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