scholarly journals Estimating the strength of selection for new SARS-CoV-2 variants

2021 ◽  
Author(s):  
Christiaan H van Dorp ◽  
Emma E Goldberg ◽  
Nicolas Hengartner ◽  
Ruian Ke ◽  
Ethan Obie Romero-Severson
Keyword(s):  
Molecular Epidemiology ◽  
Type Strain ◽  
Wild Type Strain ◽  
Sequence Data ◽  
Relative Magnitude ◽  
Global Perspective ◽  
Wild Type ◽  
Country Level ◽  
Selection For ◽  
Selection Of

A challenge to controlling the SARS-CoV-2 pandemic is the ability of the virus to adapt to its new human hosts, with novel and more transmissible strains of the virus being continually identified. Yet there are no generally accepted methods to consistently estimate the relative magnitude of the change in transmissiblity of newly emerging variants. In this paper we consider three methods for examining and quantifying positive selection of new and emerging strains of SARS-CoV-2 over an existing wild-type strain. We consider replication at the level of countries and allow for the action of other processes that can change variants' frequencies, specifically migration and drift. We apply these methods to the D614G spike mutation and the variant designated B.1.1.7, in every country where there is sufficient sequence data. For each of D614G and B.1.1.7, we find evidence for strong selection (greater than 25% increased contagiousness) in more than half of countries analyzed. Our results also shows that the selective advantages of these strains are highly heterogeneous at the country level, suggesting the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.

scholarly journals Mismatch Repair Proteins Regulate Heteroduplex Formation during Mitotic Recombination in Yeast

1998 ◽  
Vol 18 (11) ◽  
pp. 6525-6537 ◽  
Author(s):  
Wenliang Chen ◽  
Sue Jinks-Robertson
Keyword(s):  
Gene Conversion ◽  
Mismatch Repair ◽  
Sister Chromatid ◽  
Type Strain ◽  
Wild Type Strain ◽  
Sequence Data ◽  
Mitotic Recombination ◽  
Assay System ◽  
Wild Type ◽  
Mmr Proteins

Mismatch repair (MMR) proteins actively inhibit recombination between diverged sequences in both prokaryotes and eukaryotes. Although the molecular basis of the antirecombination activity exerted by MMR proteins is unclear, it presumably involves the recognition of mismatches present in heteroduplex recombination intermediates. This recognition could be exerted during the initial stage of strand exchange, during the extension of heteroduplex DNA, or during the resolution of recombination intermediates. We previously used an assay system based on 350-bp inverted-repeat substrates to demonstrate that MMR proteins strongly inhibit mitotic recombination between diverged sequences inSaccharomyces cerevisiae. The assay system detects only those events that reverse the orientation of the region between the recombination substrates, which can occur as a result of either intrachromatid crossover or sister chromatid conversion. In the present study we sequenced the products of mitotic recombination between 94%-identical substrates in order to map gene conversion tracts in wild-type versus MMR-defective yeast strains. The sequence data indicate that (i) most recombination occurs via sister chromatid conversion and (ii) gene conversion tracts in an MMR-defective strain are significantly longer than those in an isogenic wild-type strain. The shortening of conversion tracts observed in a wild-type strain relative to an MMR-defective strain suggests that at least part of the antirecombination activity of MMR proteins derives from the blockage of heteroduplex extension in the presence of mismatches.

In vivo selection of a population of Trypanosoma cruzi and clones resistant to benznidazole

Parasitology ◽  
1998 ◽  
Vol 116 (2) ◽  
pp. 165-171 ◽  
Author(s):  
S. M. F. MURTA ◽  
A. J. ROMANHA
Keyword(s):  
Mortality Rate ◽  
Trypanosoma Cruzi ◽  
Type Strain ◽  
Wild Type Strain ◽  
Wild Type ◽  
Long Term Treatment ◽  
Resistant Population ◽  
Parasitaemia Level ◽  
Selection Of

A benznidazole-resistant population of Trypanosoma cruzi, Y strain, was selected after 25 successive passages (8 months) in mice treated with a single high drug dose. Initially, the resistant parasites produced a low parasitaemia level and low mortality rate in infected mice. Thereafter, the parasitaemia level and mortality rate increased to the same value obtained for mice infected with the wild-type strain. Long-term treatment with benznidazole (100 mg/kg/day) cured 71–80% of mice infected with the wild-type strain. No cure was observed in mice infected with the selected resistant parasite population. Treatment with 500 mg/kg of benznidazole at peak parasitaemia cleared all blood parasites from mice infected with wild-type parasites. No effect on parasitaemia level was observed in mice infected with the selected parasites. Benznidazole-resistant parasites showed cross-resistance to different drugs. Contrary to wild type, all clones analysed from the resistant T. cruzi population were resistant to benznidazole. Without drug pressure the resistance phenotype of clones was far more stable than that presented by the resistant population. This work demonstrates, for the first time, the in vivo selection of a population and clones of T. cruzi resistant to benznidazole, and makes available an experimental model for the study of mechanisms of drug resistance in T. cruzi.

scholarly journals Role of Respiratory Nitrate Reductase in Ability ofPseudomonas fluorescens YT101 To Colonize the Rhizosphere of Maize

2000 ◽  
Vol 66 (9) ◽  
pp. 4012-4016 ◽  
Author(s):  
Jean-Fran�ois Ghiglione ◽  
Fran�ois Gourbiere ◽  
Patrick Potier ◽  
Laurent Philippot ◽  
Robert Lensi
Keyword(s):  
Nitrate Reductase ◽  
Type Strain ◽  
Wild Type Strain ◽  
Wild Type ◽  
Replacement Series ◽  
Gene Encoding ◽  
Direct Demonstration ◽  
Respiratory Nitrate Reductase ◽  
Selection Of

ABSTRACT Selection of the denitrifying community by plant roots (i.e., increase in the denitrifier/total heterotroph ratio in the rhizosphere) has been reported by several authors. However, very few studies to evaluate the role of the denitrifying function itself in the selection of microorganisms in the rhizosphere have been performed. In the present study, we compared the rhizosphere survival of the denitrifyingPseudomonas fluorescens YT101 strain with that of its isogenic mutant deficient in the ability to synthesize the respiratory nitrate reductase, coinoculated in nonplanted or planted soil. We demonstrated that under nonlimiting nitrate conditions, the denitrifying wild-type strain had an advantage in the ability to colonize the rhizosphere of maize. Investigations of the effect of the inoculum characteristics (density of the total inoculum and relative proportions of mutant and wild-type strains) on the outcome of the selection demonstrated that the selective effect of the plant was expressed only during the phase of bacterial multiplication and that the intensity of selection was dependent on the magnitude of this phase. Moreover, application of the de Wit replacement series technique to our results suggests that the advantage of the wild-type strain was maximal when the ratio between the two strains in the inoculum was close to 1:1. This work constitutes the first direct demonstration that the presence of a functional structural gene encoding the respiratory nitrate reductase confers higher rhizosphere competence to a microorganism.

The extraction and analysis of lipopolysaccharides from Pseudomonas aeruginosa strain PAO, and three rough mutants

1979 ◽  
Vol 25 (3) ◽  
pp. 390-398 ◽  
Author(s):  
Andrew M. Kropinski ◽  
L. C. Chan ◽  
F. H. Milazzo
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chemical Analysis ◽  
Type Strain ◽  
Wild Type Strain ◽  
Side Chains ◽  
Wild Type ◽  
Chromatographic Resolution ◽  
Selection For

Three spontaneously arising rough mutants of Pseudomonas aeruginosa have been isolated by selection for resistance to virulent lipopolysaccharide (LPS) specific bacteriophages. In addition, the first phages specific for rough mutants of P. aeruginosa were isolated. Using these phage and autoagglutination patterns in 4% NaCl and acriflavine, these mutants could be clearly distinguished from the wild-type strain and each other. Chemical analysis of the LPS together with chromatographic resolution of the polysaccharide moieties showed alterations in both O-specific side chains and core regions.

scholarly journals Development of Fatty Acid-Producing Corynebacterium glutamicum Strains

2013 ◽  
Vol 79 (21) ◽  
pp. 6776-6783 ◽  
Author(s):  
Seiki Takeno ◽  
Manami Takasaki ◽  
Akinobu Urabayashi ◽  
Akinori Mimura ◽  
Tetsuhiro Muramatsu ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Acid Production ◽  
Type Strain ◽  
Wild Type Strain ◽  
The Other ◽  
Pcr Analysis ◽  
Wild Type ◽  
Selection Of

ABSTRACTTo date, no information has been made available on the genetic traits that lead to increased carbon flow into the fatty acid biosynthetic pathway ofCorynebacterium glutamicum. To develop basic technologies for engineering, we employed an approach that begins by isolating a fatty acid-secreting mutant without depending on mutagenic treatment. This was followed by genome analysis to characterize its genetic background. The selection of spontaneous mutants resistant to the palmitic acid ester surfactant Tween 40 resulted in the isolation of a desired mutant that produced oleic acid, suggesting that a single mutation would cause increased carbon flow down the pathway and subsequent excretion of the oversupplied fatty acid into the medium. Two additional rounds of selection of spontaneous cerulenin-resistant mutants led to increased production of the fatty acid in a stepwise manner. Whole-genome sequencing of the resulting best strain identified three specific mutations (fasR20,fasA63up, andfasA2623). Allele-specific PCR analysis showed that the mutations arose in that order. Reconstitution experiments with these mutations revealed that onlyfasR20gave rise to oleic acid production in the wild-type strain. The other two mutations contributed to an increase in oleic acid production. Deletion offasRfrom the wild-type strain led to oleic acid production as well. Reverse transcription-quantitative PCR analysis revealed that thefasR20mutation brought about upregulation of thefasAandfasBgenes encoding fatty acid synthases IA and IB, respectively, by 1.31-fold ± 0.11-fold and 1.29-fold ± 0.12-fold, respectively, and of theaccD1gene encoding the β-subunit of acetyl-CoA carboxylase by 3.56-fold ± 0.97-fold. On the other hand, thefasA63upmutation upregulated thefasAgene by 2.67-fold ± 0.16-fold. In flask cultivation with 1% glucose, thefasR20 fasA63upfasA2623triple mutant produced approximately 280 mg of fatty acids/liter, which consisted mainly of oleic acid (208 mg/liter) and palmitic acid (47 mg/liter).

scholarly journals The Biocide Triclosan Selects Stenotrophomonas maltophilia Mutants That Overproduce the SmeDEF Multidrug Efflux Pump

2005 ◽  
Vol 49 (2) ◽  
pp. 781-782 ◽  
Author(s):  
Patricia Sanchez ◽  
Eduardo Moreno ◽  
Jose L. Martinez
Keyword(s):  
Type Strain ◽  
Stenotrophomonas Maltophilia ◽  
Wild Type Strain ◽  
Efflux Pump ◽  
Resistant Bacteria ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Antibiotic Resistant ◽  
Selection Of

ABSTRACT The possibility that triclosan selects Stenotrophomonas maltophilia mutants overexpressing the multidrug resistance pump SmeDEF is analyzed. Five out of 12 triclosan-selected mutants were less susceptible to antibiotics than the wild-type strain and overproduced SmeDEF. Results are discussed in relation to current debates on the potential selection of antibiotic-resistant bacteria by household biocides.

scholarly journals Effects of Mutations of RAD50, RAD51, RAD52, and Related Genes on Illegitimate Recombination in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Yasumasa Tsukamoto ◽  
Jun-ichi Kato ◽  
Hideo Ikeda
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quantitative Analysis ◽  
Structural Analysis ◽  
Recombination Rate ◽  
Type Strain ◽  
Negative Selection ◽  
Wild Type Strain ◽  
Illegitimate Recombination ◽  
Wild Type ◽  
In The Wild

Abstract To examine the mechanism of illegitimate recombination in Saccharomyces cerevisiae, we have developed a plasmid system for quantitative analysis of deletion formation. A can1 cyh2 cell carrying two negative selection markers, the CAN1 and CYH2 genes, on a YCp plasmid is sensitive to canavanine and cycloheximide, but the cell becomes resistant to both drugs when the plasmid has a deletion over the CAN1 and CYH2 genes. Structural analysis of the recombinant plasmids obtained from the resistant cells showed that the plasmids had deletions at various sites of the CAN1-CYH2 region and there were only short regions of homology (1-5 bp) at the recombination junctions. The results indicated that the deletion detected in this system were formed by illegitimate recombination. Study on the effect of several rad mutations showed that the recombination rate was reduced by 30-, 10-, 10-, and 10-fold in the rad52, rad50, mre11, and xrs2 mutants, respectively, while in the rud51, 54, 55, and 57 mutants, the rate was comparable to that in the wild-type strain. The rad52 mutation did not affect length of homology at junction sites of illegitimate recombination.

scholarly journals The role of Zur-regulated lipoprotein A in bacterial morphology, antimicrobial susceptibility, and production of outer membrane vesicles in Acinetobacter baumannii

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nayeong Kim ◽  
Hyo Jeong Kim ◽  
Man Hwan Oh ◽  
Se Yeon Kim ◽  
Mi Hyun Kim ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Mutant Strain ◽  
Antimicrobial Susceptibility ◽  
Type Strain ◽  
Wild Type Strain ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Wild Type ◽  
Bacterial Morphology

Abstract Background Zinc uptake-regulator (Zur)-regulated lipoprotein A (ZrlA) plays a role in bacterial fitness and overcoming antimicrobial exposure in Acinetobacter baumannii. This study further characterized the zrlA gene and its encoded protein and investigated the roles of the zrlA gene in bacterial morphology, antimicrobial susceptibility, and production of outer membrane vesicles (OMVs) in A. baumannii ATCC 17978. Results In silico and polymerase chain reaction analyses showed that the zrlA gene was conserved among A. baumannii strains with 97–100% sequence homology. Recombinant ZrlA protein exhibited a specific enzymatic activity of D-alanine-D-alanine carboxypeptidase. Wild-type A. baumannii exhibited more morphological heterogeneity than a ΔzrlA mutant strain during stationary phase. The ΔzrlA mutant strain was more susceptible to gentamicin than the wild-type strain. Sizes and protein profiles of OMVs were similar between the wild-type and ΔzrlA mutant strains, but the ΔzrlA mutant strain produced 9.7 times more OMV particles than the wild-type strain. OMVs from the ΔzrlA mutant were more cytotoxic in cultured epithelial cells than OMVs from the wild-type strain. Conclusions The present study demonstrated that A. baumannii ZrlA contributes to bacterial morphogenesis and antimicrobial resistance, but its deletion increases OMV production and OMV-mediated host cell cytotoxicity.

scholarly journals FixJ family regulator AcfR of Azorhizobium caulinodans is involved in symbiosis with the host plant

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Liu ◽  
Xue Bai ◽  
Yan Li ◽  
Haikun Zhang ◽  
Xiaoke Hu
Keyword(s):  
Signal Transduction ◽  
Host Plant ◽  
Type Strain ◽  
Wild Type Strain ◽  
Response Regulator ◽  
Azorhizobium Caulinodans ◽  
Wild Type ◽  
Response Regulators ◽  
Free Living ◽  
Two Component

Abstract Background A wide variety of bacterial adaptative responses to environmental conditions are mediated by signal transduction pathways. Two-component signal transduction systems are one of the predominant means used by bacteria to sense the signals of the host plant and adjust their interaction behaviour. A total of seven open reading frames have been identified as putative two-component response regulators in the gram-negative nitrogen-fixing bacteria Azorhizobium caulinodans ORS571. However, the biological functions of these response regulators in the symbiotic interactions between A. caulinodans ORS571 and the host plant Sesbania rostrata have not been elucidated to date. Results In this study, we identified and investigated a two-component response regulator, AcfR, with a phosphorylatable N-terminal REC (receiver) domain and a C-terminal HTH (helix-turn-helix) LuxR DNA-binding domain in A. caulinodans ORS571. Phylogenetic analysis showed that AcfR possessed close evolutionary relationships with NarL/FixJ family regulators. In addition, six histidine kinases containing HATPase_c and HisKA domains were predicted to interact with AcfR. Furthermore, the biological function of AcfR in free-living and symbiotic conditions was elucidated by comparing the wild-type strain and the ΔacfR mutant strain. In the free-living state, the cell motility behaviour and exopolysaccharide production of the ΔacfR mutant were significantly reduced compared to those of the wild-type strain. In the symbiotic state, the ΔacfR mutant showed a competitive nodule defect on the stems and roots of the host plant, suggesting that AcfR can provide A. caulinodans with an effective competitive ability for symbiotic nodulation. Conclusions Our results showed that AcfR, as a response regulator, regulates numerous phenotypes of A. caulinodans under the free-living conditions and in symbiosis with the host plant. The results of this study help to elucidate the involvement of a REC + HTH_LuxR two-component response regulator in the Rhizobium-host plant interaction.

scholarly journals Mab_3083c Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of Mycobacterium abscessus

2021 ◽  
Vol 9 (4) ◽  
pp. 676
Author(s):  
Ting-Yu Liu ◽  
Sheng-Hui Tsai ◽  
Jenn-Wei Chen ◽  
Yu-Ching Wang ◽  
Shiau-Ting Hu ◽  
...  
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Opportunistic Pathogen ◽  
Mycobacterium Abscessus ◽  
Colony Morphology ◽  
Clinical Strain ◽  
Immunocompromised Patients ◽  
Clinical Infection ◽  
Wild Type ◽  
Sliding Motility

Mycobacterium abscessus is an opportunistic pathogen causing human diseases, especially in immunocompromised patients. M. abscessus strains with a rough morphotype are more virulent than those with a smooth morphotype. Morphotype switch may occur during a clinical infection. To investigate the genes involved in colony morphotype switching, we performed transposon mutagenesis in a rough clinical strain of M. abscessus. A morphotype switching mutant (smooth) named mab_3083c::Tn was obtained. This mutant was found to have a lower aggregative ability and a higher sliding motility than the wild type strain. However, its glycopeptidolipid (GPL) content remained the same as those of the wild type. Complementation of the mutant with a functional mab_3083c gene reverted its morphotype back to rough, indicating that mab_3083c is associated with colony morphology of M. abscessus. Bioinformatic analyses showed that mab_3083c has a 75.4% identity in amino acid sequence with the well-characterized ribonuclease J (RNase J) of M. smegmatis (RNase JMsmeg). Complementation of the mutant with the RNase J gene of M. smegmatis also switched its colony morphology from smooth back to rough. These results suggest that Mab_3083c is a homologue of RNase J and involved in regulating M. abscessus colony morphotype switching.

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