The Sensitization of Legionella pneumophila to Some Antibiotics by Reserpine and Anti-Legionella Effects of Different BenzofuranoneDerivatives

Legionella pneumophila is a dangerous pathogenic bacterium can cause serious infectious diseases especially in hospitalized immunocompromised patients. This bacteriumis shown to be resistant against different antibiotics. Resistance against a wide range of antibiotics is usually mediated by efflux pump in bacteria. Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds of cells which excreted antibiotics outside the cells. However, synthesis of new anti-Legionella compounds or selection of resistant modulating agents are useful strategy to combat with L. pneumophilain the future. In this study the antibacterial activity of some benzofuranone derivatives have been investigated by disk diffusion method against L. pneumophila. Also the sensitivity of this test strain was evaluated against 40 antibiotics and the combination effect of reserpine at a sub-inhibitory concentration was further studied with these antibiotics using disk diffusion method with some modifications. Among the different synthetic compounds which were tested against L. pneumophila, the most antibacterial activity was observed for compounds 1j and 1m which contain hydroxyl and methoxy groups on the C-6 and C-7 positionsagainst L. pneumophila. To evaluate whether efflux pumps are active in L. pneumophila or not an efflux inhibitor (reserpine) was tested in combination of different antibiotics against this test strain. Reserpine significantly enhanced the antibacterial activities of kanamycin, nitrofurantoin, co-trimoxazole, erythromycin, ofloxacillin, gentamycin, rifampin, ciprofloxacin, nalidixic acid, minocycline, tobramycin, and amikacin against L. pneumophilawhich shows the resistances to these antibiotics are mediated by efflux system in this bacterium.