Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia.

Abstract αB-Crystallin plays an important part in cataract development. A novel mutation (R11H) was previously detected by our group. In the present study, we set out to investigate the possible molecular mechanism by which the R11H mutation causes cataract. We found that the mutant αB-crystallin exhibits folding defects, decreased surface hydrophobicity and enhanced chaperone-like activity compared with the wild-type αB-crystallin. The mutant protein shows nearly the same molecular mass and thermal stability as the wild-type form. Transfection studies revealed that the R11H mutant was remarkably similar to the wild-type protein in its subcellular distribution, but has an abnormal ability to induce cell apoptosis. These results suggest that the changes in hydrophobic exposure and the abnormal ability to induce programmed cell death of the mutant protein are likely to be responsible for the onset of cataract.

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Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occuring [sic] mutants associated with hyperphenylalaninemia

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.93.9.4519-b ◽

1996 ◽

Vol 93 (9) ◽

pp. 4519-4519

Keyword(s):

Wild Type ◽

Type Form ◽

Wild Type Form

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The Potential for SARS-CoV-2 to Evade Both Natural and Vaccine-induced Immunity

10.1101/2020.12.13.422567 ◽

2020 ◽

Cited By ~ 1

Author(s):

Emily Shang ◽

Paul Axelsen

Keyword(s):

Human Infection ◽

Antibody Binding ◽

Spike Protein ◽

Wild Type ◽

Binding Interface ◽

Naturally Occurring ◽

Binding Interfaces ◽

Induced Immunity ◽

Wild Type Form

SARS-CoV-2 attaches to the surface of susceptible cells through extensive interactions between the receptor binding domain (RBD) of its spike protein and angiotensin converting enzyme type 2 (ACE2) anchored in cell membranes. To investigate whether naturally occurring mutations in the spike protein are able to prevent antibody binding, yet while maintaining the ability to bind ACE2 and viral infectivity, mutations in the spike protein identified in cases of human infection were mapped to the crystallographically-determined interfaces between the spike protein and ACE2 (PDB entry 6M0J), antibody CC12.1 (PDB entry 6XC2), and antibody P2B-2F6 (PDB entry 7BWJ). Both antibody binding interfaces partially overlap with the ACE2 binding interface. Among 16 mutations that map to the RBD:CC12.1 interface, 11 are likely to disrupt CC12.1 binding but not ACE2 binding. Among 12 mutations that map to the RBD:P2B-2F6 interface, 8 are likely to disrupt P2B-2F6 binding but not ACE2 binding. As expected, none of the mutations observed to date appear likely to disrupt the RBD:ACE2 interface. We conclude that SARS-CoV-2 with mutated forms of the spike protein may retain the ability to bind ACE2 while evading recognition by antibodies that arise in response to the original wild-type form of the spike protein. It seems likely that immune evasion will be possible regardless of whether the spike protein was encountered in the form of infectious virus, or as the immunogen in a vaccine. Therefore, it also seems likely that reinfection with a variant strain of SARS-CoV-2 may occur among people who recover from Covid-19, and that vaccines with the ability to generate antibodies against multiple variant forms of the spike protein will be necessary to protect against variant forms of SARS-CoV-2 that are already circulating in the human population.

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Synergism of imipenem with fosfomycin associated with the active cell wall recycling and heteroresistance in Acinetobacter calcoaceticus-baumannii complex

Scientific Reports ◽

10.1038/s41598-021-04303-7 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Uthaibhorn Singkham-in ◽

Tanittha Chatsuwan

Keyword(s):

Cell Wall ◽

De Novo ◽

Acinetobacter Calcoaceticus ◽

Active Cell ◽

Wild Type ◽

Cell Wall Metabolism ◽

Carbapenem Resistant ◽

Type Form ◽

Wild Type Form ◽

Cell Wall Recycling

AbstractThe carbapenem-resistant Acinetobacter calcoaceticus-baumannii (ACB) complex has become an urgent threat worldwide. Here, we determined antibiotic combinations and the feasible synergistic mechanisms against three couples of ACB (A. baumannii (AB250 and A10), A. pittii (AP1 and AP23), and A. nosocomialis (AN4 and AN12)). Imipenem with fosfomycin, the most effective in the time-killing assay, exhibited synergism to all strains except AB250. MurA, a fosfomycin target encoding the first enzyme in the de novo cell wall synthesis, was observed with the wild-type form in all isolates. Fosfomycin did not upregulate murA, indicating the MurA-independent pathway (cell wall recycling) presenting in all strains. Fosfomycin more upregulated the recycling route in synergistic strain (A10) than non-synergistic strain (AB250). Imipenem in the combination dramatically downregulated the recycling route in A10 but not in AB250, demonstrating the additional effect of imipenem on the recycling route, possibly resulting in synergism by the agitation of cell wall metabolism. Moreover, heteroresistance to imipenem was observed in only AB250. Our results indicate that unexpected activity of imipenem on the active cell wall recycling concurrently with the presence of heteroresistance subpopulation to imipenem may lead to the synergism of imipenem and fosfomycin against the ACB isolates.

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Inactivation of the selB Gene in Methanococcus maripaludis: Effect on Synthesis of Selenoproteins and Their Sulfur-Containing Homologs

Journal of Bacteriology ◽

10.1128/jb.185.1.107-114.2003 ◽

2003 ◽

Vol 185 (1) ◽

pp. 107-114 ◽

Cited By ~ 42

Author(s):

Michael Rother ◽

Isabella Mathes ◽

Friedrich Lottspeich ◽

August Böck

Keyword(s):

Gene Product ◽

Formate Dehydrogenase ◽

Selenium Supplementation ◽

Wild Type ◽

Methanococcus Maripaludis ◽

Translation Factor ◽

Type Form ◽

And Function ◽

Sulfur Containing ◽

Wild Type Form

ABSTRACT The genome of Methanococcus maripaludis harbors genes for at least six selenocysteine-containing proteins and also for homologs that contain a cysteine codon in the position of the UGA selenocysteine codon. To investigate the synthesis and function of both the Se and the S forms, a mutant with an inactivated selB gene was constructed and analyzed. The mutant was unable to synthesize any of the selenoproteins, thus proving that the gene product is the archaeal translation factor (aSelB) specialized for selenocysteine insertion. The wild-type form of M. maripaludis repressed the synthesis of the S forms of selenoproteins, i.e., the selenium-independent alternative system, in selenium-enriched medium, but the mutant did not. We concluded that free selenium is not involved in regulation but rather a successional compound such as selenocysteyl-tRNA or some selenoprotein. Apart from the S forms, several enzymes from the general methanogenic route were affected by selenium supplementation of the wild type or by the selB mutation. Although the growth of M. maripaludis on H2/CO2 is only marginally affected by the selB lesion, the gene is indispensable for growth on formate because M. maripaludis possesses only a selenocysteine-containing formate dehydrogenase.

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Seed Production and Germination of Eight Cultivars and the Wild Type of Ruellia tweediana: A Potentially Invasive Ornamental

Journal of Environmental Horticulture ◽

10.24266/0738-2898-21.3.137 ◽

2003 ◽

Vol 21 (3) ◽

pp. 137-143 ◽

Cited By ~ 4

Author(s):

Sandra B. Wilson ◽

Laurie K. Mecca

Keyword(s):

Seed Production ◽

Invasive Plant ◽

Temperature Treatment ◽

Native Plant ◽

Wild Type ◽

Type Form ◽

Storage Studies ◽

Exotic Pest ◽

Exotic Pest Plant ◽

Wild Type Form

Abstract Seed production and the influence of light and temperature on germination were determined for eight cultivars and the wild type form of Mexican petunia (Ruellia tweediana Griseb). The wild type form of R. tweediana has been ranked by the Florida Exotic Pest Plant Council as a Category I invasive plant, meaning it has invaded and is disrupting native plant communities in Florida. The cultivar ‘Purple Showers’ did not set any seed. Peak flowering and seed production for other cultivars generally occurred in August with ‘Morado Chi’, ‘Chi Chi’, and the wild type plants producing approximately three times the amount of seed produced by ‘Katie Pink’, ‘Katie Purple’, ‘Katie White’, and ‘Snow White’. For seed germination, significant cultivar x light interactions occurred for each temperature treatment. Some germination was observed at each temperature except for ‘Katie Purple’, ‘Katie Variegated’, and ‘Katie White’ at 33C (91.4F) without light. Regardless of cultivar or provision of light, 94-100% germination occurred at 30/20C (86/68F), with the exception of ‘Katie Purple’ (65%), ‘Katie Variegated’ (54%), and ‘Katie White’ (83%) without light. At 15, 24 or 33C (59, 75.2, and 91.4F), germination was generally greatest for ‘Chi Chi’ (with or without light) and ‘Morado Chi’ (with light). In parallel greenhouse studies, where seeds were germinated in pots containing a soilless medium, highest germination was achieved by ‘Chi Chi’, ‘Katie Pink’, ‘Katie Variegated’ and ‘Morado Chi’, while significantly lower germination was achieved by wild type plants (55%) by day 14. Storage studies demonstrated that germination of seed collected from the wild type and ‘Chi Chi’ plants began to decrease between 6 and 12 months when maintained at 24C (75.2F) but had equal (‘Chi Chi’) or higher (wild type) germination when maintained at 4C (39.2F) for 12 months.

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Biofilm-Constructing Variants of Paraburkholderia phytofirmans PsJN Outcompete the Wild-Type Form in Free-Living and Static Conditions but Not In Planta

Applied and Environmental Microbiology ◽

10.1128/aem.02670-18 ◽

2019 ◽

Vol 85 (11) ◽

Cited By ~ 1

Author(s):

Marine Rondeau ◽

Qassim Esmaeel ◽

Jérôme Crouzet ◽

Pauline Blin ◽

Isabelle Gosselin ◽

...

Keyword(s):

Wild Type ◽

In Planta ◽

Free Living ◽

Iron Sulfur Cluster ◽

Content Type ◽

Iron Sulfur ◽

Type Form ◽

Static Conditions ◽

Wild Type Form

ABSTRACT Members of the genus Burkholderia colonize diverse ecological niches. Among the plant-associated strains, Paraburkholderia phytofirmans PsJN is an endophyte with a broad host range. In a spatially structured environment (unshaken broth cultures), biofilm-constructing specialists of P. phytofirmans PsJN colonizing the air-liquid interface arose at high frequency. In addition to forming a robust biofilm in vitro and in planta on Arabidopsis roots, those mucoid phenotypic variants display a reduced swimming ability and modulate the expression of several microbe-associated molecular patterns (MAMPs), including exopolysaccharides (EPS), flagellin, and GroEL. Interestingly, the variants induce low PR1 and PDF1.2 expression compared to that of the parental strain, suggesting a possible evasion of plant host immunity. We further demonstrated that switching from the planktonic to the sessile form did not involve quorum-sensing genes but arose from spontaneous mutations in two genes belonging to an iron-sulfur cluster: hscA (encoding a cochaperone protein) and iscS (encoding a cysteine desulfurase). A mutational approach validated the implication of these two genes in the appearance of variants. We showed for the first time that in a heterogeneous environment, P. phytofirmans strain PsJN is able to rapidly diversify and coexpress a variant that outcompete the wild-type form in free-living and static conditions but not in planta. IMPORTANCE Paraburkholderia phytofirmans strain PsJN is a well-studied plant-associated bacterium known to induce resistance against biotic and abiotic stresses. In this work, we described the spontaneous appearance of mucoid variants in PsJN from static cultures. We showed that the conversion from the wild-type (WT) form to variants (V) correlates with an overproduction of EPS, an enhanced ability to form biofilm in vitro and in planta, and a reduced swimming motility. Our results revealed also that these phenotypes are in part associated with spontaneous mutations in an iron-sulfur cluster. Overall, the data provided here allow a better understanding of the adaptive mechanisms likely developed by P. phytofirmans PsJN in a heterogeneous environment.

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