Functional trihydroxyl germanium moiety in THGP confers novel enzyme activity inhibition abilities while also...

THGP [3-(trihydroxygermyl) propanoic acid], an organogermanium compound, has been confirmed to exert multifaceted effects in mammalian and eukaryotic cells. Focusing on the characteristic trihydroxyl germanium moiety of THGP, we aimed to discover its novel pharmacological abilities and effects against multidrug-resistant Acinetobacter baumannii, a prokaryote with critical implications on global public health. In all assays, spectrometric determinations (OD) were conducted using a 96-well microtiter plate: OD489 for β-lactamase activity, OD600 for bacterial mass, OD570 for biofilm mass, OD340 for alcohol dehydrogenase (ADH) activity, and OD460 for dehydrogenases-NAD(P)-NAD(P)H system activity. THGP was observed to exhibit β-lactamase activity inhibition ability, which actually presents synergistic effects with cephem antibiotics against A. baumannii. We also revealed ADH activity inhibition ability, which contributes to the antiproliferative effect of THGP, a weak organic acid, against A. baumannii. However, low permeability of THGP through the bacterial cell because of its high hydrophilicity seemed to attenuate this intracellular effect. Furthermore, THGP was postulated to possess preventive effects on biofilm formation at sub-MIC (below the minimum inhibitory concentration) via an unknown mechanism. To our knowledge, this study is the first to report the antimicrobial effects of an organogermanium compound and demonstrates the inhibition abilities of THGP against two ubiquitous enzymes in pathogenic bacteria. However, the findings of this study are insufficient for clinical applications. Further studies are warranted to promote the development of clinically useful organogermanium compounds. Nevertheless, our findings provide important baseline information for future exploratory studies.