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Antimicrobial Agents and Chemotherapy, August 2005, p. 3468-3473, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3468-3473.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Bactericidal and Morphological Effects of NE-2001, a Novel Synthetic Agent Directed against Helicobacter pylori

Guofei Dai,^2, Ni Cheng,^1, Lei Dong,¹ Mutsumi Muramatsu,¹ Shudong Xiao,³ Ming-Wei Wang,^2,4* and De-Xu Zhu^1*

State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing 210093, People's Republic of China,¹ The National Center for Drug Screening, Shanghai Institute of Materia Medica and Graduate School, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China,² Laboratory of Gastroenterology, Ministry of Public Health, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, People's Republic of China,³ Shanghai East Best Biopharmaceutical Enterprises Co., Ltd., Shanghai 200233, People's Republic of China⁴

Received 3 July 2004/ Returned for modification 5 September 2004/ Accepted 5 May 2005

The antibacterial activities of NE-2001 were tested against 24 clinical isolates of Helicobacter pylori and compared with those of amoxicillin, clarithromycin, metronidazole, and furazolidone. The MIC₅₀ and MIC₉₀ of this synthetic compound on the isolates were 8 and 16 µg/ml, respectively. This action was highly selective against Helicobacter pylori; there was a >4-fold difference between the concentration of NE-2001 required to inhibit the growth of Helicobacter pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of Helicobacter pylori (ATCC43504) to NE-2001 at the MIC (4 µg/ml), or at a greater concentration, resulted in an extensive loss of viability. The phenomenon was also observed at pH levels between 3.0 and 7.0. When two clinical Helicobacter pylori strains were successively cultured at subinhibitory concentrations of NE-2001, no significant changes in the bactericidal effects were found. The morphological alterations of Helicobacter pylori cells (ATCC43504), exposed to NE-2001 at various concentrations for 6 h, were observed using transmission electron microcopy. The bacterium displayed features such as swelling, vacuole-like structures in the cytoplasm, and cell destruction following exposure to NE-2001. The efficacy of NE-2001 was maintained when evaluated in eight clinical isolates resistant to metronidazole and five isolates resistant to both metronidazole and clarithromycin (MIC ranging between 4 and 16 µg/ml). The above-described results suggest that NE-2001 may have the potential to be developed as a candidate agent for the treatment of Helicobacter pylori infection.

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* Corresponding author. Mailing address for De-Xu Zhu: Department of Biochemistry, Nanjing University, Nanjing 210093, P.R. China. Phone: 86 25 8359 2405. Fax: 86 25 83324605. E-mail: zjq{at}nju.edu.cn. Mailing address for Ming-Wei Wang: The National Center for Drug Screening, Shanghai 201203, P.R. China. Phone: 86 21 5080 0598. Fax: 86 21 5080 0721. E-mail: center{at}mail.shcnc.ac.cn.

G.D. and N.C. contributed equally to the work.

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Antimicrobial Agents and Chemotherapy, August 2005, p. 3468-3473, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3468-3473.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.