, 1994) and for the alkaliphilic bacteria Bacillus firmus OF4 (Hicks buy Fostamatinib & Krulwich, 1990) and Bacillus sp. TA2.A1 (Keis et al., 2006). Whereas in alkaliphilic bacteria subunit ɛ has been pinpointed as the PMF-dependent regulator of ATP hydrolysis activity, in P. denitrificans and related Alphaproteobacteria,

recently, a new intrinsic inhibitor protein, termed subunit ζ, was found (Morales-Ríos et al., 2010). However, as database search did not reveal any homologue of subunit ζ in mycobacteria, we regard subunit ɛ as the most likely candidate for this regulatory task. Our results show that mycobacterial ATP synthase is blocked in the ATP hydrolysis direction and also suggest that any potential small-molecule inhibitor acting on mycobacterial ATP synthase should interfere with the ATP synthesis reaction in order to be considered as a drug candidate. An approach as used for the development of antiischemia drugs blocking ATP hydrolysis Compound Library chemical structure (Harmann et al., 2004) is thus not expected to be a promising strategy for the development of new antimycobacterial drugs. However, activation of the latent ATP hydrolysis activity may lead to depleted cellular ATP levels and decrease the bacteria’s viability. Compounds that can specifically

relieve the blockage of ATP hydrolysis may thus be potential drug candidates. Experiments to clarify this point and to understand the molecular mechanism of ATP hydrolysis blockage in slow-growing mycobacteria are under way in our laboratory. A.C.H. and D.B. gratefully acknowledge financial support from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO-ECHO grant 700.55.017). “
“Haemophilus parasuis is one of the most important bacterial diseases of pigs worldwide. The lack of a vaccine against a broad mTOR inhibitor spectrum of strains and the limitation of antimicrobial

susceptibility hamper the control of disease. In this study, we cloned the constant regions of gamma heavy chains and kappa light chain of pig lymphocytes in frame with the variable regions of heavy and light chains of mouse monoclonal antibody 1D8, which reacts with all 15 serotypes of H. parasuis and has neutralizing activity. The constructed mouse–pig chimeric antibody was expressed in Pichia pastoris. Results demonstrated that the expressed chimeric antibody inhibited the growth of H. parasuis in vitro. Furthermore, the experiments in mice showed that chimeric antibody increased survival rate of the mice compared with that of the control group (P < 0.05). Importantly, the chimeric antibody partially protected piglets against H. parasuis infection according to the clinical lesion scores and PCR results of H. parasuis in the tissues from piglets of the chimeric antibody-inoculated group and the PBS group. In summary, our results demonstrated that the mouse–pig chimeric antibody could be a therapeutic candidate to prevent the H. parasuis infection and control the prevalence of disease.