Activity of nisin against Streptococcus pneumoniae, in vitro, and in a mouse infection model.
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Biomedical subjects
Publications and source records attributed to R Novick.
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As more lung transplantations are performed, many patients will suffer graft failure and will be considered for retransplantation. This article reviews the case management reports of four patients who received lung or heart/lung retransplantation, with overall disappointing results. The pros and cons of lung retransplantation are discussed.
The synthesis of several exoproteins, including protein A (SpA) in Staphylococcus aureus is coordinately regulated by the agr locus. Different constructs of the SpA-encoding gene (spa) were introduced into Agr+ and Agr- derivatives of a spa- strain of S. aureus. Plasmid-located spa with deletions at the 3' end expressed a truncated SpA which was almost exclusively extracellular and which confirmed the role of C-terminal region X in cell-wall binding. In the Agr- host, the production of SpA was elevated severalfold. Transcriptional and translational fusions were constructed to study the agr- mediated regulation of spa gene expression. Translational fusions of a beta-lactamase (Bla)-encoding ApR reporter gene with the spa promoter and N-terminal coding sequences expressed elevated levels of Bla activity in the Agr- host. In contrast, a transcriptional fusion of the spa gene with a promoter of the positively regulated staphylococcal epidermolytic toxin A (ETA)-encoding gene synthesized higher levels of SpA in an Agr+ host, as compared to Agr-. Moreover, the synthesis of SpA in the Agr+ strain was switched on during the transition from the exponential to stationary phase in a similar fashion to ETA itself. These data strongly indicate that the regulation of both SpA and ETA occurs at the transcriptional level in S. aureus. The agr-regulated spa promoter was defined by deletion analysis and by transcript mapping.
The gene coding for toxic shock syndrome toxin-1 in S. aureus was inactivated by allelic replacement in two TSS-associated strains. One mutant derived from FRI1169 (a non-enterotoxigenic strain) lacked virulence in the rabbit uterine chamber infection model. This suggests that TSST-1 is the only determinant produced by this strain that can induce the symptoms of shock in rabbits. A novel method for allelic replacement involving transduction of plasmid integrants is described.
Primary cardiac tumours are uncommon entities, and myxoma is the most common, comprising about 50% of all these neoplasms. A case of a 43-year-old woman with right atrial myxoma and a shunt through a patent foramen ovale producing severe cyanosis is reported.
The genomic organization of five small multicopy staphylococcal plasmids comprising the pT181 family has been analyzed. In addition to pT181, the family presently includes the streptomycin resistance plasmid pS194 and the chloramphenicol resistance plasmids pC221, pC223, and pUB112. Although they belong to five different incompatibility groups, the five plasmids have similar basic replicons, use the same basic copy control mechanism, and have a common structural organization. It has been demonstrated previously that pT181 and pC221 encode trans-active replication proteins (RepC and RepD, respectively) which specifically recognize the respective plasmid's origin of replication in both cases is initiated by site-specific nicking and 3' extension. The other three plasmids in this family encode similar replication proteins; 63% of the predicted amino acid residues are identical for all five and the least similar pair shows 75% identity at the amino acid level. However, despite this homology, the replication proteins and origins of replication of different members in this family did not show cross complementation in vivo. Outside of the basic replicon, which comprises about one-third of each plasmid's genome, functional organization is also conserved. The resistance determinants are all located in the same position, immediately downstream of the replication protein coding sequence, and all are transcribed in the same direction. The three chloramphenicol resistance determinants encode highly homologous chloramphenicol transacetylases which are unrelated to the tet and str gene products. Three of the five plasmids form relaxation complexes and the involved genome segments are closely related. The other two are not homologous to these three in the corresponding region, but are homologous to each other and encode a site-specific recombinase, Pre. It is suggested that the replication, resistance, and relaxation complex regions of these plasmids can be regarded as conserved segments ("cassettes") assembled in various combinations, but always with the same spatial arrangement.
Elimination of plasmids from regenerating S. aureus protoplasts occurred when the regeneration medium contained sucrose but not when it contained sodium succinate. This difference was caused by the occurrence of cell division prior to regeneration of the cell wall on sucrose but not on succinate. Coexisting compatible plasmids were cured independently; coexisting incompatible plasmids were cured jointly. These results support the hypothesis that plasmid pools exist as physically sequestered units in protoplasts and that curing is a consequence of the segregation of such units during abnormal division of wall-less organisms.
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The process of division in Staphylococcus aureus was examined by phase-contrast microscopy. The organisms appeared to divide in three alternating perpendicular planes, with sister cells remaining attached to each other after division. The resulting point of attachment was usually not exactly at the point corresponding to the center of the previous septal disk. Moreover, sister cells often changed position with respect to one another while still remaining attached. These factors are apparently responsible for the irregularity of staphylococcal clumps. Studies with penicillin and the examination of thin sections in the electron microscope confirm the conclusion, based upon light microscopy, that successive divisions in S. aureus occur in perpendicular planes.
Protein-deoxyribonucleic acid relaxation complexes have been demonstrated for six Staphylococcus aureus plasmids out of sixteen examined. Four of these encode stretomycin resistence, have molecular weights of about 2.7 x 10(6), and are isolated as supercoiled molecules that are virtally 100% relaxable by treatment with sodium dodecyl sulfate. It is probable that these four isolates represent a single widely disseminated plasmid species. The other two plasmids showing relaxation complexes have molecular weights of about 3 x 10(6) and encode chloramphenicol resistance. The complexes in these cases are unstable, and it has not been possible to induce more than 50% relaxation by any of the standard treatments. Ten other plasmids do not show detectable complexes. These include three penicillinase plasmids, four tetracycline-resistance plasmids, one plasmid carrying kanamycin-neomycin resistance, and finally, two chloramphenicol-resistance plasmids.
The quantity of penicillinase plasmid deoxyribonucleic acid (DNA) in various strains of Staphylococcus aureus has been determined by DNA-DNA reassociation kinetics. Specifically, 32P- or 125I-labeled denatured probes of purified plasmid DNA were reassociated in the presence of denatured DNAs isolated from the bacterial strains in question. The number of plasmid copies per cell was calculated from the effect of the latter nucleic acid samples on the reassociation rate of the radiolabeled probe. Among the S. aureus strains examined were monoplasmid, diplasmid and replication-defective representatives, and the effect of temperature on wild-type plasmid content was also investigated.
A series of studies were performed on a Staphylococcus aureus strain thought to contain a pencillinase plasmid integrated into the host chromosome. Reassociation kinetics analysis of whole-cell deoxyribonucleic acid (DNA) in the presence of pure radioactive plasmid DNA revealed that plasmid-specific sequences were present at about 1 copy per chromosome equivalent as compared to 3.6 copies for the same plasmid in its autonomous state. Consistent with this observation was the finding that penicillinase activity was lower for the former strain than for the latter. It was shown further that the plasmid-specific sequences cosedimented on neutral sucrose gradients with fragments of whole-cell DNA many times larger than the plasmid. These two findings were taken as strongly confirmatory of the integrated state. Analysis of whole-cell ribonucleic acid for the presence of plasmid-specific messengers revealed that these were present in approximately the amounts expected on the basis of the DNA study.