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Polyphosphate Synthetic Activity of Polyphosphate:AMP Phosphotransferase in Acinetobacter johnsonii 210A. Hiromichi Itoh, 2004.Polyphosphate:AMP phosphotransferase (PAP) has been identified as an enzyme that catalyzes the phosphorylation of AMP with inorganic polyphosphates [poly(P)] as phosphate donors . We found that the purified PAP of Acinetobacter johnsonii 210A has poly(P) synthetic activity . The PAP catalyzes the dephosphorylation of ADP and processively synthesizes poly(P) of 200 to 700 residues . Comparatively lower concentrations of MgCl2 (20 mM) were required to obtain optimum poly(P) synthetic activity, whereas higher concentrations of MgCl2 (100 mM) were necessary for optimum PAP activity . ADP is preferred over GDP as a phosphate donor for poly(P) synthesis . The Km and Vmax values for ADP in the poly(P) synthetic activity of PAP were 8.3 mM and 55 µmol min–1 mg–1, respectively . We concluded that the PAP of A . johnsonii 210A is a novel type of poly(P) kinase that uses ADP and GDP as substrates . Oral Efficacy of a Respiratory Syncytial Virus Inhibitor in Rodent Models of Infection. Christopher Cianci, 2004.BMS-433771 is a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro . Mechanism of action studies have demonstrated that BMS-433771 halts virus entry through inhibition of F protein-mediated membrane fusion . BMS-433771 also exhibited in vivo efficacy following oral administration in a mouse model of RSV infection (C . Cianci, K . Y . Yu, K . Combrink, N . Sin, B . Pearce, A . Wang, R . Civiello, S . Voss, G . Luo, K . Kadow, E . Genovesi, B . Venables, H . Gulgeze, A . Trehan, J . James, L . Lamb, I . Medina, J . Roach, Z . Yang, L . Zadjura, R . Colonno, J . Clark, N . Meanwell, and M . Krystal, Antimicrob . Agents Chemother . 48:413-422, 2004) . In this report, the in vivo efficacy of BMS-433771 against RSV was further examined in the BALB/c mouse and cotton rat host models of infection . By using the Long strain of RSV, prophylactic efficacy via oral dosing was observed in both animal models . A single oral dose, administered 1 h prior to intranasal RSV inoculation, was as effective against infection as a 4-day b.i.d . dosing regimen in which the first oral dose was given 1 h prior to virus inoculation . Results of dose titration experiments suggested that RSV infection was more sensitive to inhibition by BMS-433771 treatment in the BALB/c mouse host than in the cotton rat . This was reflected by the pharmacokinetic and pharmacodynamic analysis of the efficacy data, where the area under the concentration-time curve required to achieve 50% of the maximum response was  7.5-fold less for mice than for cotton rats . Inhibition of RSV by BMS-433771 in the mouse is the result of F1-mediated inhibition, as shown by the fact that a virus selected for resistance to BMS-433771 in vitro and containing a single amino acid change in the F1 region was also refractory to treatment in the mouse host . BMS-433771 efficacy against RSV infection was also demonstrated for mice that were chemically immunosuppressed by cyclophosphamide treatment, indicating that compound inhibition of the virus did not require an active host immune response .
Geobacter sulfurreducens Has Two Autoregulated lexA Genes Whose Products Do Not Bind the recA Promoter: Differing Responses of lexA and recA to DNA Damage. Mónica Jara, 2003.The Escherichia coli LexA protein was used as a query sequence in TBLASTN searches to identify the lexA gene of the  -proteobacterium Geobacter sulfurreducens from its genome sequence . The results of the search indicated that G . sulfurreducens has two independent lexA genes designated lexA1 and lexA2 . A copy of a dinB gene homologue, which in E . coli encodes DNA polymerase IV, is present downstream of each lexA gene . Reverse transcription-PCR analyses demonstrated that, in both cases, lexA and dinB constitute a single transcriptional unit . Electrophoretic mobility shift assays with purified LexA1 and LexA2 proteins have shown that both proteins bind the imperfect palindrome GGTTN2CN4GN3ACC found in the promoter region of both lexA1 and lexA2 . This sequence is also present upstream of the Geobacter metallireducens lexA gene, indicating that it is the LexA box of this bacterial genus . This palindrome is not found upstream of either the G . sulfurreducens or the G . metallireducens recA genes . Furthermore, DNA damage induces expression of the lexA-dinB transcriptional unit but not that of the recA gene . However, the basal level of recA gene expression is dramatically higher than that of the lexA gene . Likewise, the promoters of the G . sulfurreducens recN, ruvAB, ssb, umuDC, uvrA, and uvrB genes do not contain the LexA box and are not likely to bind to the LexA1 or LexA2 proteins . G . sulfurreducens is the first bacterial species harboring a lexA gene for which a constitutive expression of its recA gene has been described .
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