scholarly journals NONSENSE MOTILITY MUTANTS IN SALMONELLA TYPHIMURIUM

Genetics ◽  
1973 ◽  
Vol 73 (2) ◽  
pp. 229-245
Author(s):  
Patricia S Vary ◽  
Bruce A D Stocker
Keyword(s):  
Salmonella Typhimurium ◽  
Structural Component ◽  
Phase 1 ◽  
Avoidance Reaction ◽  
Wild Type ◽  
Amber Mutation ◽  
Small Minority ◽  
Complementation Groups ◽  
Basal Apparatus ◽  
Derivatives Of

ABSTRACT Of 313 motility-deficient mutants isolated from an LT2 his(amber) strain fixed in phase 1 by gene vh2-, 25 regained motility when amber or ochre suppressors were introduced, in F' factors or by transduction. The fla mutants (23 amber, 1 ochre) fell in complementation groups A, B, C, F, K, a new group, M, and at least one further new group; the hypothesis of a fla gene which specifies only an RNA structural component of a flagellum-synthesizing basal apparatus is disproven for the corresponding genes. Hfr and transductional crosses confirmed gene assignments from complementation and indicated that flaM and another new fla locus map near H1. A small minority of motile bacteria were detectable in many of the amber fla mutants. In groups A and F some pairs of amber fla mutants complemented each other, and perhaps each of these groups corresponds to more than one structural gene. The suppressed derivatives of a mutant with an amber mutation in H1 made flagella morphologically and serologically indistinguishable from wild-type flagella. A slowspreading but flagellate mutant showed mainly non-translational motility in broth, and in a viscocs medium the bacteria reversed very frequently; its amber mutation, probably near H1, is inferred to cause a defect in chemotaxis, so that the bacteria give the avoidance reaction continuously.

scholarly journals Episomic suppression of phenotype in Salmonella

1964 ◽  
Vol 5 (2) ◽  
pp. 269-281 ◽  
Author(s):  
P. F. Smith-Keary ◽  
G. W. P. Dawson
Keyword(s):  
Gene Expression ◽  
Salmonella Typhimurium ◽  
Uv Irradiation ◽  
Complementation Group ◽  
Wild Type ◽  
Complementation Groups

1. An auxotroph of Salmonella typhimurium, pro-401, was isolated in a strain that was unstable at the su-leuA locus. The auxotrophy of pro-401 is probably due to the attachment of a controlling episome to the proline region of the genome where it suppresses gene expression.2. The controlling episome frequently transposes over short distances so that all clones consist of cells, mixed for the site at which the controlling episome is attached; homologous transductions yield prototrophs.3. The controlling episome can transpose to a different complementation group; homologous transductions yield abortive transductants; syntrophism occurs between cells that are ‘mutant’ in different complementation groups to give reversions consisting entirely of auxotrophic cells which are called auxotrophic reversions.4. The controlling episome transposes over very short distances and never to beyond the limits of this proline region of the genome; no wild-type reversions were found.5. The controlling episome can be located at relatively distant proline sites in different clones; prototrophs from transductions between clones that are separated by many subculturings can be 100 times more frequent than from homologous transductions.6. The controlling episome has its frequency of transposition to different complementation groups increased by UV; irradiation increases the frequency of auxotrophic reversions.7. The controlling episome continues to transpose in stored cells.8. The pattern of reversions of pro-401 is different in these studies from its pattern two years previously. This is discussed.

scholarly journals THE NATURE OF GENETIC INSTABILITY IN AUXOTROPHS OF SALMONELLA TYPHIMURIUM REQUIRING CYSTEINE OR METHIONINE AND RESISTANT TO INHIBITION BY 1,2,4-TRIAZOLE

Genetics ◽  
1978 ◽  
Vol 89 (3) ◽  
pp. 439-451
Author(s):  
A J Kingsman ◽  
D A Smith
Keyword(s):  
Enzyme Activity ◽  
Salmonella Typhimurium ◽  
Uv Irradiation ◽  
Genetic Instability ◽  
Genetic Material ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Regulatory Regions ◽  
Gene Regulatory ◽  
Derivatives Of

ABSTRACT We tested the hypothesis that unstable suppression of auxotrophy in triazole-resistant derivatives of Cym- mutants of Salmonella typhimurium is due to reversible insertion at the Cym- site of genetic material originating in the cysALKptsHI region. We have shown that the unstable phenotype was co-transducible with markers in the cysCDHIJ region. The suppression of the Cym phenotype was recA dependent and frequencies of segregation were affected by UV irradiation. Restored enzyme activity in suppressed strains was determined by wild-type enzyme, suggesting that the unstable regions are located in cys gene regulatory regions. These results support the hypothesis. In contradiction, we found no evidence for a deletion in the cysALKptsHI region.

scholarly journals Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rebecca L. Brocato ◽  
Steven A. Kwilas ◽  
Robert K. Kim ◽  
Xiankun Zeng ◽  
Lucia M. Principe ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Phase 1 ◽  
Severe Disease ◽  
Disease Model ◽  
Wild Type ◽  
Jet Injection ◽  
Syrian Hamsters ◽  
Dna Targeting

AbstractA worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

scholarly journals CHROMOSOMAL BASIS OF THE MEROZYGOSITY IN A PARTIALLY DIPLOID MUTANT OF PNEUMOCOCCUS

Genetics ◽  
1975 ◽  
Vol 80 (4) ◽  
pp. 667-678
Author(s):  
Mary Lee S Ledbetter ◽  
Rollin D Hotchkiss
Keyword(s):  
High Efficiency ◽  
Point Mutations ◽  
Resistant Mutant ◽  
Chromosomal Marker ◽  
Structural Abnormality ◽  
C Cells ◽  
Wild Type ◽  
Chromosomal Locus ◽  
Low Efficiency ◽  
Derivatives Of

ABSTRACT A sulfonamide-resistant mutant of pneumococcus, sulr-c, displays a genetic instability, regularly segregating to wild type. DNA extracts of derivatives of the strain possess transforming activities for both the mutant and wild-type alleles, establishing that the strain is a partial diploid. The linkage of sulr-c to strr-61, a stable chromosomal marker, was established, thus defining a chromosomal locus for sulr-c. DNA isolated from sulr-c cells transforms two mutant recipient strains at the same low efficiency as it does a wild-type recipient, although the mutant property of these strains makes them capable of integrating classical "low-efficiency" donor markers equally as efficiently as "high efficiency" markers. Hence sulr-c must have a different basis for its low efficiency than do classical low efficiency point mutations. We suggest that the DNA in the region of the sulr-c mutation has a structural abnormality which leads both to its frequent segregation during growth and its difficulty in efficiently mediating genetic transformation.

scholarly journals Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

scholarly journals Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults

2019 ◽  
Vol 222 (4) ◽  
pp. 572-582 ◽  
Author(s):  
Louis Fries ◽  
Iksung Cho ◽  
Verena Krähling ◽  
Sarah K Fehling ◽  
Thomas Strecker ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Response ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Phase 1 ◽  
Healthy Adults ◽  
Wild Type ◽  
Dose Ranging ◽  
Further Development ◽  
Human Vaccine

Abstract Background Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development. Methods A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year postdosing. Results All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP immunoglobulin G titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type Zaire EBOV (ZEBOV) or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year. Conclusions Ebola virus GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted.

Sequence analysis of operator mutants of the phase-1 flagellin-encoding gene, flic, in salmonella typhimurium

Gene ◽  
1989 ◽  
Vol 85 (1) ◽  
pp. 221-226 ◽  
Author(s):  
Yoshihiro H. Inoue ◽  
Kazuhiro Kutsukake ◽  
Tetsuo Iino ◽  
Shigeru Yamaguchi
Keyword(s):  
Sequence Analysis ◽  
Salmonella Typhimurium ◽  
Phase 1 ◽  
Encoding Gene

scholarly journals exrB: amalB-linked gene inEscherichia coliB involved in sensitivity to radiation and filament formation

1974 ◽  
Vol 23 (2) ◽  
pp. 175-184 ◽  
Author(s):  
Joseph Greenberg ◽  
Leonard J. Berends ◽  
John Donch ◽  
Michael H. L. Green
Keyword(s):  
Escherichia Coli ◽  
Normal Growth ◽  
Filament Formation ◽  
Wild Type ◽  
Sensitive Mutant ◽  
Γ Radiation ◽  
Linked Gene ◽  
Derivatives Of

SUMMARYPAM 26, a radiation-sensitive mutant ofEscherichia colistrain B, is described. Its properties are attributable to a mutation in a gene,exrB, which is cotransducible withmalB. It differs fromuvrA(alsomalB-linked) derivatives of strain B in being sensitive to 1-methyl-3-nitro-1-nitroso-guanidine and γ-radiation, and in being able to reactivate UV-irradiated phage T3. It differs fromexrA(alsomalB-linked) derivatives of strain B in forming filaments during the course of normal growth as well as after irradiation. WhenexrBwas transduced into a K12 (lon+) strain, filaments did not form spontaneously. Three-point transductions established the order of markers asmet A malB exrB. Based on an analysis of the frequency of wild-type recombinants in a reciprocal transduction betweenexrAandexrBstrains, it was inferred that they are not isogenic and that the order of markers ismalB exrA exrB.

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