However, increasing antibiotic resistance is threatening to undermine the effective treatment of shigellosis. Berberine is a natural isoquinoline alkaloid found in medicinal herbs, such as Rhizoma coptidis (Huanglian). Berberine Selleck FDA approved Drug Library has demonstrated a number of biological activities, including antisecretory, anti-inflammatory, antibacterial, antimalarial, antitumor and anticholesterol activities, and is widely used in the treatment of bacterial diarrhea and intestinal parasite infections in many countries (Yamamoto

et al., 1993; Iwasa et al., 1998). It has been shown that berberine has the properties of A–T base-specific DNA partial intercalation and generating singlet oxygen as a functional photosensitizer (Pilch et al., 1997; Brezova et al., 2004). Accumulated evidence suggests several mechanisms that may explain the antimicrobial activity of berberine. It has been reported that berberine interferes with the adherence of streptococci (Sun et al., 1988). It has also been demonstrated that berberine directly inhibits some Vibrio cholerae and Escherichia coli enterotoxins (Sack & Froehlich, 1982). In Leishmania donovani,

berberine exhibited an inhibitory action on macromolecular biosynthesis (Ghosh et al., 1985). Although berberine has been used in the treatment of gastrointestinal disorders, especially shigelleosis, for some time in Linsitinib supplier China (Chang, 1959), its effect on the causative agent of shigellosis is not yet well understood. Transcript profiling based on microarray technology enables us to investigate the response of the bacterial genome to antimicrobial agents, which provides useful clues to the mechanism of

action of the agents (Fu et al., 2007). In this study, whole-genome DNA microarray was used to examine transcriptional responses elicited by berberine in Shigella flexneri. Shigella flexneri 2a strain 301 (Sf301), our sequenced strain, was used in this study (Jin et al., 2002). The bacterium was grown at 37 °C with shaking (200 r.p.m.) on cation-adjusted Mueller–Hinton broth (caMHB), a medium recommended by the Clinical and Laboratory Standards Institute (CLSI) for susceptibility testing. Berberine chloride (BC) purchased from Sigma-Aldrich CYTH4 was resolved in dimethyl sulfoxide (DMSO) and diluted with caMHB. The minimal inhibitory concentration (MIC) of BC for Sf301 was determined according to the CLSI broth macrodilution methods for bacteria that grow aerobically (Clinical and Laboratory Standards Institute, 2006). Sf301, taken from a 24-h culture in caMHB, was inoculated in the same medium until reaching an OD600 nm of about 0.05. The cultures were then allowed to continue growing at 37 °C with shaking. When they were grown to early exponential growth phase (an OD600 nm of about 0.3), BC was added from the 400 × stock dissolved in DMSO into the cultures to give final concentrations of 160, 320, and 640 μg mL−1. A control with only DMSO was also included. The final DMSO concentration for all conditions was 1% v/v.