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Biomedical subjects

M Gough

Publications and source records attributed to M Gough.

At least 73 records · Page 4Linked to original sources
PubMed1977

Effect of mutant host RNA polymerase on the bifunctional activities of P22 gene c1.

The product of phage P22 gene c1 has two functions: (1) it promotes synthesis of repressor and (2) during the first minutes of infection it retards expression of some lytic genes. We call the second, negative function "c1 retardation". We investigated c1 retardation in a mutant host of Salmonella typhimurium that is resistant to rifampicin and carries an altered RNA polymerase. No c1 retardation of DNA synthesis was detectable in this host after infection with wild-type phages. This elimination of the normally detectable c1 function leads to the conclusion that the mutant RNA polymerase interferes with the expression of c1 gene activity. Wild-type genes form clear plaques on the mutant host. Mutants of P22 called cly were isolated by others. These mutants form turbid plaques on the altered RNA polymerase host. Infections with P22 cly in the mutant host resulted in detectable c1 retardation. The cly mutation therefore restores c1 activity in a host which wild-type c1 is not expressed. Two spontaneous mutants were isolated from the mutant host. These two strains allowed partial expression of c1 retardation, although they remained rifampicin resistant. We interpret our data to indicate that expression of the normal functions of the gene c1 product requires an interaction of that product with the host RNA polymerase.

DNA-Directed RNA Polymerases↗
PubMed1977

Regulation of Bacteriophage P22 DNA synthesis and repressor levels in P22cly infections.

A rifampin-resistant mutant of Salmonella typhimurium carries an altered RNA polymerase. Wild-type (c+) phage P22 displays clear plaques and a reduced lysogenization frequency on this mutant host. The cly mutants of P22 were isolated on the basis of their ability to lysogenize such mutant hosts. Two classes of regulatory events, both of which are dependent on P22 gene c1 activity, are necessary for the establishment of lysogeny in P22. The positive events culminate in repressor synthesis; the negative events cause a retardation in phage DNA synthesis. Neither the positive nor the negative events are observed in P22c+ infections of the mutant host. Both effects are found in P22cly infections of the mutant host. Observable results of both the negative and the positive events are exaggerated in P22cly infections of wild-type hosts as compared to P22c+ infections. The cly mutation apparently increases the positive and negative regulatory events so that they are detectable in the mutant host and exaggerated in wild-type hosts. Possible mechanisms that result in the high frequency of lysogenization that characterizes the cly mutation and the nature of the cly mutation are discussed.

DNA, Viral↗
PubMed1976

Site c27 in phage P22 and control of the pathway to lysogeny.

Phage P22 mutation c27 defines a site required for establishment , but not maintenance of repressor synthesis. This study confirms that P22 c27 is able to synthesize repressor if active repressor is present. An interaction involving gene products of c1 and c3 and the site c27 retards expression of the lytic genes of P22. Mutations in gene c1 eliminate the retardation of lytic gene expression, but c27 does not alleviate the retardation. These results are used to construct a model that postulates that binding of c1 and c3 products to DNA at or near c27 is sufficient to cause retardation of lytic gene expression. The functioning of c27 is contrasted to that of the analogous cy mutants of lambda. The effect of the c27 mutation upon alleviation of "cl repression" was studied in a partial revertant of Salmonella typhimurium Pox-1 in which c1 repression is exaggerated. The higher frequency of lysogenization seen in the mutant host is related to enhanced cl repression.

Base Sequence↗
PubMed1976

UV sensitivity of a nonrepressor regulatory protein of bacteriophage P22.

The product of phage P22 gene c1 has two functions: it promotes synthesis of P22 repressor and it retards expression of some lytic genes. We present evidence that this product is inactivated in UV-irradiated hosts. The conditions for inactivation of c1 product include a functional DNA recombination system involving the host recA gene.

Bacterial Proteins↗
PubMed1975

Further structural and functional analogies between the repressor regions of phages P22 and lambda.

Mutants of P22 which have been located in the c2 repressor gene were examined. The most rightward "c2 mutation" was found to define a site that is necessary only for the establishment and not for the maintenance of repressor synthesis. We conclude that this site c27 is an analog of cy mutants in phage lambda which define a promotor for repression establishment (pre). The K5 mutation of P22 maps between c27 and all other c2 mutants. Examination of its biological behavior and direct measurement of repressor activity show that K5 does not affect c2 repression. A model to explain these findings implies that c27 and K5 affect transcripts of opposite directions. P22 c1 mutants do not allow c2 repressor synthesis and we conclude that the activity of c1 product (and presumably c3 product) at the site defined by c27 is necessary for repressor synthesis. The combined activity of c1 and c3 product at c27 is postulated to promote repressor synthesis and block transcription of vegatative phage genes to the right of K5. After repressor synthesis has been established, another site analogous to lambda prm is sufficient for repressor synthesis and c27 is no longer required. These observations and conclusions point to a very close analogy between repressor synthesis and control in phages P22 and lambda.

Carrier Proteins↗
PubMed1975

Altered DNA synthesis in a mutant of Salmonella typhimurium that channels bacteriophage P22 toward lysogeny.

Pox-1, a mutant of Salmonella typhimurium, strongly channels P22 toward lysogeny. Viral DNA synthesis in this slow-growing mutant is delayed to a greater extent than viral protein synthesis. The relative enhancement of c2 repressor synthesis results in much higher repressor/DNA synthesis ratios in Pox-1 than in wild-type cells. This probably accounts for the high frequency of lysogenization.

DNA Replication↗
PubMed1975

Host influence on the activity of genes c1 and c3 in regulating the decision between lysis and lysogency in bacteriophage P22.

A Polymyxin B-sensitive mutant of Salmonella typhimurium (Pox-1) channels all infecting wild-type P22 toward lysogenization. The efficiency of this channeling is sufficiently high that P22c+ (wild type) cannot form plaques on Pox-1; phage mutants defective in repressor synthesis (P22c1, c2, c3) or refractory toward repressor (P22vir B) can form plaques. The lytic growth of all phages which have a functional c1 gene is retarded in Pox-1; this retardation is seen even in phages which cannot make repressor. We present experiments which are consistent with the explanation that the retardation is an exaggeration of a normal regulatory event. In a wild-type host, P22 genes c1 and c3 products, host RNA polymerase, and other host factors (?) interact at a promotor site (c27) IN THE PHAGE DNA. This interaction promotes repressor synthesis and represses transcription of lytic genes. In the mutant Pox-1, a host product involved in viral DNA synthesis and transcription is altered. The altered host product results in stronger retardation of lytic gene transcription. The importance of this interaction in the decision between lysis and lysogeny is discussed. The mutant Pox-1 alters the expression or activity of another phage gene. Gene c3 product is absolutely required for lysogenization in this host, although it is not so required in wild-type S. typhimurium.

Bacteriolysis↗
PubMed1974

Attenuation of rhinovirus type 15: relation of illness to plaque size.

Rhinovirus type 15 passaged three times in WI-38 cells produced illness in only one of 35 volunteers, but infection resulted in formation of significant quantities of antibodies in the serums of 100%, and in nasal secretions of 89%, of infected volunteers. The inoculum contained large- (60%) and small- (40%) plaque variants. "Purified" large- and small-plaque inocula were prepared, and each was administered to 20 volunteers. There was a significant association of illness with the small-plaque inocula (P < 0.01) but the incidence of infection, quantitative virus shedding patterns, and mean serum and nasal secretory antibodies were not significantly different between the two groups. These findings suggest that plaque size may be an in vitro marker of attenuation of illness production by rhinoviruses.

Antibody Formation↗
PubMed1974

Mutant of Salmonella typhimurium that channels infecting bacteriophage P22 toward lysogenization.

A slowly growing, polymyxin-sensitive mutant of Salmonella typhimurium was isolated. Wild-type phage P22 form plaques on the mutant at 5 x 10(-4), the frequency observed on wild-type hosts. All P22 clear mutants form plaques with near normal frequency. The inability of the mutant to form plaques is correlated with an increase in lysogenization frequency. The cause of the increased lysogenization frequency is not known, but it is not the result of overproduction of cyclic adenosine 5'-monophosphate.

Cyclic AMP↗
PubMed1970

Requirement for a functional int product in temperature inductions of prophage P22 ts mnt.

Prophage P22 ts mnt was found to be inducible by high temperatures. This property was maintained when the ts mnt allele was recombined into a phage that cannot synthesize phage deoxyribonucleic acid at high temperature. Prophage P22 int ts mnt, on the other hand, was not inducible at high temperature. This result leads to the suggestion that the int enzyme, which is involved in excision, is regulated by the product of gene mnt.

Crosses, Genetic↗