Motoshi Suzuki et al. (2007) International Worm Meeting "Efficient laser-induced gene expression in C. elegans."

Shunsuke Yuba, Yasuhiro Kamei, Yoichi Oda, Motoshi Suzuki, Shin Takagi

[International Worm Meeting, 2007]

Tissue-specific promoters have been widely used to analyze the function of a given gene by driving its expression in transgenic animals in vivo</I>. Such ectopic expression experiments using tissue-specific promoters, however, are sometimes limited by inherent properties of the promoters to drive gene expression in a restricted temporal-spatial expression pattern. Transgenic lines in which the expression of a gene can be regulated both in space and time at our discretion would be useful to study various developmental problems. Although heat-shock promoters have been employed to induce gene expression at a specified time, usual heat-shock procedures do not allow spatial control of gene expression. If heat can be deposited locally, spatial control can be achieved in heat-shock promoter-driven transgenic animals. Previous studies have shown that irradiation of a sub-lethal dose of visible laser light (440 nm) can be used to induce heat shock responses in targeted single cells of C. elegans</I> (Stringham and Candido, 1993) and other organisms. There is, however, a concern that the laser light of 440 nm, which was originally designed for cell ablation experiments, may have detrimental effects to cells. As absorption coefficient of water is higher in the infrared (IR) region, the IR light would heat up cells efficiently. Since most biomolecules do not absorb the IR light, it also would be relatively harmless to cells. Therefore, irradiation with the IR laser microbeam would be more suited for inducing gene expression mediated by heat-shock responses, compared with that of 440 nm dye laser. Based on these rationales, we are now trying to apply a newly developed IR-LEGO (IR-laser evoked gene operation) system to C. elegans</I>. We will report on our attempts to regulate gene expression in targeted single cells.

Mohammad H et al. (2017) J Med Chem "Phenylthiazole Antibacterial Agents Targeting Cell Wall Synthesis Exhibit Potent Activity In Vitro and In Vivo against Vancomycin-resistant Enterococci."

Mayhoub AS, Seleem MN, Peters CE, Zhang J, Cushman MS, Pogliano K, Pogliano J, Chen L, Oldfield E, Mohammad H, Cooper BR, Younis W

[J Med Chem, 2017]

The emergence of antibiotic-resistant bacterial species, such as vancomycin-resistant enterococci (VRE), necessitates the development of new antimicrobials. Here, we investigate the spectrum of antibacterial activity of three phenylthiazole-substituted aminoguanidines. These compounds possess potent activity against VRE, inhibiting growth of clinical isolates at concentrations as low as 0.5 g/mL. The compounds exerted a rapid bactericidal effect, targeting cell wall synthesis. Transposon mutagenesis suggested three possible targets: YubA, YubB (undecaprenyl diphosphate phosphatase (UPPP)) and YubD. Both UPPP as well as undecaprenyl diphosphate synthase were inhibited by compound 1. YubA and YubD are annotated as transporters and may also be targets since 1 collapsed the proton motive force in membrane vesicles. Using Caenorhabditis elegans, we demonstrate that two compounds (1, 3, at 20 g/mL) retain potent activity in vivo, significantly reducing the burden of VRE in infected worms. Taken altogether, the results indicate that compounds 1 and 3 warrant further investigation as novel antibacterial agents against drug-resistant enterococci.