SummaryPseudomonas aeruginosa produces three types of bacteriocins: R-, F-and S-type pyocins. The S-type pyocin is a colicin-like protein, whereas the R-type pyocin resembles a contractile but non-flexible tail structure of bacteriophage, and the F-type a flexible but non-contractile one. As genetically related phages exist for each type, these pyocins have been thought to be variations of defective phage. In the present study, the nucleotide sequence of R2 pyocin genes, along with those for F2 pyocin, which are located downstream of the R2 gene cluster on the chromosome of P. aeruginosa PAO1, was analysed in order to elucidate the relationship between the pyocins and bacteriophages. The results clearly demonstrated that the R-type pyocin is derived from a common ancestral origin with P2 phage and the Ftype from l phage. This notion was supported by identification of a lysis gene cassette similar to those for bacteriophages. The gene organization of the R2 and F2 pyocin gene cluster, however, suggested that both pyocins are not simple defective phages, but are phage tails that have been evolutionarily specialized as bacteriocins. A systematic polymerase chain reaction (PCR) analysis of P. aeruginosa strains that produce various subtypes of R and F pyocins revealed that the genes for every subtype are located between trpE and trpG in the same or very similar gene organization as for R2 and F2 pyocins, but with alterations in genes that determine the receptor specificity.
Department of Preventive Medicine, ShinshuUniversity Graduate School of Medicine-Di (2-ethylhexyl) phthalate (DEHP) exposure is thought to lead to hepatocellular hypertrophy and hyperplasia in rodents mediated via peroxisome proliferator-activated receptor alpha (PPARα). A recent study revealed that long-term exposure to relatively low-dose DEHP (0.05%) caused liver tumors including hepatocellular carcinomas, hepatocellular adenomas, and chologiocellular carcinomas at a higher incidence in Pparα-null mice (25.8%) than in wild-type mice (10.0%). Using tissues with hepatocellular adenoma, microarray (Affymetrix MOE430A) as well as, in part, real-time quantitative PCR analysis was conducted to elucidate the mechanisms of the adenoma formation resulting from DEHP exposure in both genotyped mice. The microarray profiles showed that the up-or downregulated genes were quite different between hepatocellular adenoma tissues of wild-type and Pparα-null mice exposed to DEHP. The gene expressions of apoptotic peptidase activating factor 1 (Apaf1) and DNA-damage-inducible 45 alpha (Gadd45a) were increased in the hepatocellular adenoma tissues of wild-type mice exposed to DEHP, whereas they were unchanged in corresponding tissues of Pparα-null mice. On the other hand, the expressions of cyclin B2 and myeloid cell leukemia sequence 1 were increased only in the hepatocellular adenoma tissues of Pparα-null mice. Taken together, DEHP may induce hepatocellular adenomas, in part, via suppression of G2/M arrest regulated by Gadd45a and caspase 3-dependent apoptosis in Pparα-null mice, but these genes may not be involved in tumorigenesis in the wild-type mice. In contrast, the expression level of Met was notably increased in the liver adenoma tissue of wild-type mice, which may suggest the involvement of Met in DEHPinduced tumorigenesis in wild-type mice. (J Occup Health 2008; 50: 169-180)
Rts1, a large conjugative plasmid originally isolated from Proteus vulgaris, is a prototype for the IncT plasmids and exhibits pleiotropic thermosensitive phenotypes. Here we report the complete nucleotide sequence of Rts1. The genome is 217,182 bp in length and contains 300 potential open reading frames (ORFs). Among these, the products of 141 ORFs, including 9 previously identified genes, displayed significant sequence similarity to known proteins. The set of genes responsible for the conjugation function of Rts1 has been identified. A broad array of genes related to diverse processes of DNA metabolism were also identified. Of particular interest was the presence of tus-like genes that could be involved in replication termination. Inspection of the overall genome organization revealed that the Rts1 genome is composed of four large modules, providing an example of modular evolution of plasmid genomes.Rts1 is a low-copy-number kanamycin resistance plasmid originally isolated from a clinical strain of Proteus vulgaris (56). Its molecular mass was originally estimated to be about 140 MDa (29). This large plasmid is the prototype for the T incompatibility group (9) and expresses pleiotropic thermosensitive phenotypes in autonomous replication (13, 58), conjugative transfer (56), host cell growth (12, 57), and restriction of T-even phages (28,32,66).As in many large plasmids of gram-negative bacteria, Rts1 requires two elements for its autonomous replication, a replication initiation protein encoded by the plasmid (repA) and a short segment containing the replication origin, ori (30,34,59). Because the replication of this mini-Rts1 plasmid is stable at 37°C but is inhibited at 42°C in Escherichia coli (30), as observed for Rts1 (56, 58), the replication machinery of Rts1 itself is thermosensitive. A locus termed tdi (temperature-dependent instability) has also been identified as another locus responsible for the temperature sensitivity (48, 55), but its real physiological role in the replication (or maintenance) of Rts1 is unknown.As for the temperature-sensitive effect on host cell growth, Terawaki et al. (57) first reported that Rts1 inhibits its host cell growth at 42°C but not at 37°C. Since then, two loci responsible for this phenotype have been identified, tsg (43, 47) and hig (60-62). Since the tsg locus contains no open reading frame (ORF), the AT-rich DNA segment itself is thought to be responsible for the thermosensitivity of host cell growth. On the other hand, the hig locus encodes a system belonging to the proteic killer family, where the HigB and HigA proteins function as a toxin and an antitoxin, respectively. The temperaturesensitive host cell growth conferred by the hig system is mediated by selectively killing the host that has lost all copies of Rts1 at a nonpermissive temperature (postsegregation killing).Conjugation of Rts1 is also thermosensitive, but the temperature range for conjugation differs from that for replication, efficient at 25°C but not at 37°C (56). Thus, the thermosensitivity of ...
-In order to verify the influence of the rat age on hepatotoxicity, male Sprague-Dawley rats of 6 (young) and 12 (adult) weeks of age were orally administered acetaminophen (APAP), isoniazid (INH), or carbon tetrachloride (CCl4). Liver samples were obtained in a time-course manner, and changes in gene expression examined by an Affymetrix GeneChip. APAP caused more prominent hepatic injury with respect to pathology and blood biochemistry in adults than in young rats, whereas no obvious agerelated differences were observed in INH-or CCl4-treated rats. Comparing gene expression in control rats, CYP3A13 was higher and GSTY2c was lower in adults, suggesting that production of the active metabolite of APAP is higher and its detoxification is lower in adults. The total amount of glutathione and total SH in rat liver was found to be higher in adult rats whereas the extent of its reduction by APAP was larger in adults. A detailed analysis of genes showing age-related differences revealed that some of them were different not in their extent but in their time course, i.e., the stress responses occurred earlier in the young than in the adult, resulting in a difference at 24 hr after dosing. These results suggest that the age-related difference in toxicity would be attributed to a higher expression of CYP3A13, producing the active metabolite of APAP as well as the lower expression of the detoxification enzyme, GSTY2c, in adult rats. Furthermore, these differences affect the time course of APAP toxicity. The present study clearly depicts the advantage of the multi-time, multi-dose protocol employed in our project for analyzing the mechanism of toxicity by gene expression profiling.
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