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Applied and Environmental Microbiology, February 2008, p. 1243-1249, Vol. 74, No. 4
0099-2240/08/$08.00+0     doi:10.1128/AEM.02151-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rottlerin Inhibits Chlamydial Intracellular Growth and Blocks Chlamydial Acquisition of Sphingolipids from Host Cells{triangledown}

Pooja Shivshankar, Lei Lei, Jie Wang, and Guangming Zhong*

Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229

Received 1 September 2007/ Accepted 6 December 2007

We report that rottlerin, a plant-derived compound known to inhibit various mammalian kinases, profoundly inhibited chlamydial growth in cell culture with a minimal inhibition concentration of 1 µM. The inhibition was effective even when rottlerin was added as late as the middle stage of chlamydial infection cycle, against multiple Chlamydia species, and in different host cell lines. Pretreatment of host cells with rottlerin prior to infection also blocked chlamydial growth, suggesting that rottlerin targets host factors. Moreover, rottlerin did not alter the chlamydial infection rate and did not directly target chlamydial protein synthesis and secretion. The rottlerin-mediated inhibition of chlamydial replication and inclusion expansion correlated well with the rottlerin-induced blockade of host cell sphingolipid trafficking from the Golgi apparatus into chlamydial inclusions. These studies not only allowed us to identify a novel antimicrobial activity for rottlerin but also allowed us to uncover a potential mechanism for rottlerin inhibition of chlamydial growth.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229. Phone: (210) 567-1169. Fax: (210) 567-0293. E-mail: Zhongg{at}uthscsa.edu

{triangledown} Published ahead of print on 14 December 2007.

Applied and Environmental Microbiology, February 2008, p. 1243-1249, Vol. 74, No. 4
0099-2240/08/$08.00+0     doi:10.1128/AEM.02151-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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