cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.17076468
title: Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination

description: Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation's effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3–2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.
DOI: 10.6084/m9.figshare.17076468.v1
title: Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination

description: Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation's effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3–2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.
DOI: 10.21233/2wxy-fm50
title: Bourdim pollen dataset

description: Raw data for the Bourdim pollen dataset submitted to the Neotoma Paleoecology Database. Data is available through the landing page in JSON format. The landing page referenced by the DOI also contains links to publications and a map-based viewer for the dataset. The Neotoma Paleoecology Database maintains a homepage at https://www.neotomadb.org.
DOI: 10.6084/m9.figshare.18858199
title: Methicillin-resistant <i>Staphylococcus aureus</i> in China: a multicentre longitudinal study and whole-genome sequencing

description: The aim of this study was to investigate the genomic epidemiology of MRSA in China to identify predominant lineages and their associated genomic and phenotypic characteristics. In this study, we conducted whole-genome sequencing on 565 MRSA isolates from 7 provinces and municipalities of China between 2014 and 2020. MRSA isolates were subjected to MLST, <i>spa</i> typing, SCC<i>mec</i> typing, analysis of virulence determinants and antimicrobial susceptibility testing. Among 565 MRSA isolates tested, clonal complex (CC) 59 (31.2%), CC5 (23.4%) and CC8 (13.63%) were the major lineages, and the clonal structure was dominated by ST59-t437-IV (14.9%), ST239-t030-III (6.4%) and ST5-t2460-II (6.0%), respectively. Of note, CC8, the predominant lineage in 2014–2015, was replaced by CC59 after 2016. Interestingly, the extension and unstable structure of the CC5 population was observed, with ST5-t311-II, ST764-t1084-II, ST5-t2460-II and ST764-t002-II existing complex competition. Further analysis revealed that virulence determinant profiles and antibiograms were closely associated with the clonal lineage. The CC59 MRSA was less resistant to most tested antimicrobials and carried fewer resistance determinants. But rifampicin resistance and mupirocin resistance were closely linked with CC8 and CC5, respectively. MRSA isolates conservatively carried multiple virulence genes involved in various functions. PVL encoding genes were more common in ST338, CC30, CC398, ST8 and CC22, while <i>tsst</i>-1 was associated with ST5. In conclusion, the community-associated CC59-ST59-t437-IV lineage was predominant in China, with diverse clonal isolates alternately circulating in various geographical locations. Our study highlights the need for MRSA surveillance in China to monitor changes in MRSA epidemiology.
DOI: 10.6084/m9.figshare.18858199.v2
title: Methicillin-resistant <i>Staphylococcus aureus</i> in China: a multicentre longitudinal study and whole-genome sequencing

description: The aim of this study was to investigate the genomic epidemiology of MRSA in China to identify predominant lineages and their associated genomic and phenotypic characteristics. In this study, we conducted whole-genome sequencing on 565 MRSA isolates from 7 provinces and municipalities of China between 2014 and 2020. MRSA isolates were subjected to MLST, <i>spa</i> typing, SCC<i>mec</i> typing, analysis of virulence determinants and antimicrobial susceptibility testing. Among 565 MRSA isolates tested, clonal complex (CC) 59 (31.2%), CC5 (23.4%) and CC8 (13.63%) were the major lineages, and the clonal structure was dominated by ST59-t437-IV (14.9%), ST239-t030-III (6.4%) and ST5-t2460-II (6.0%), respectively. Of note, CC8, the predominant lineage in 2014–2015, was replaced by CC59 after 2016. Interestingly, the extension and unstable structure of the CC5 population was observed, with ST5-t311-II, ST764-t1084-II, ST5-t2460-II and ST764-t002-II existing complex competition. Further analysis revealed that virulence determinant profiles and antibiograms were closely associated with the clonal lineage. The CC59 MRSA was less resistant to most tested antimicrobials and carried fewer resistance determinants. But rifampicin resistance and mupirocin resistance were closely linked with CC8 and CC5, respectively. MRSA isolates conservatively carried multiple virulence genes involved in various functions. PVL encoding genes were more common in ST338, CC30, CC398, ST8 and CC22, while <i>tsst</i>-1 was associated with ST5. In conclusion, the community-associated CC59-ST59-t437-IV lineage was predominant in China, with diverse clonal isolates alternately circulating in various geographical locations. Our study highlights the need for MRSA surveillance in China to monitor changes in MRSA epidemiology.
DOI: 10.6084/m9.figshare.19114469
title: Resistance profiling of <i>Aspergillus fumigatus</i> to olorofim indicates absence of intrinsic resistance and unveils the molecular mechanisms of acquired olorofim resistance

description: Olorofim (F901318) is a new antifungal currently under clinical development that shows both <i>in vitro</i> and <i>in vivo</i> activity against a number of filamentous fungi including <i>Aspergillus fumigatus</i>. In this study, we screened <i>A. fumigatus</i> isolates for intrinsic olorofim-resistant <i>A. fumigatus</i> and evaluated the ability of <i>A. fumigatus</i> to acquire an olorofim-resistant phenotype. No intrinsic resistance was found in 975 clinical <i>A. fumigatus</i> isolates. However, we found that isolates with increased olorofim MICs (&gt; 8 mg/L) could be selected using a high number of conidia and olorofim exposure under laboratory conditions. Assessment of the frequency of acquired olorofim resistance development of <i>A. fumigatus</i> was shown to be higher than for voriconazole but lower than for itraconazole. Sequencing the <i>PyrE</i> gene of isogenic isolates with olorofim MICs of &gt;8 mg/L identified various amino acid substitutions with a hotspot at locus G119. Olorofim was shown to have reduced affinity to mutated target protein dihydroorotate dehydrogenase (DHODH) and the effect of these mutations was proven by introducing the mutations directly in <i>A. fumigatus</i>. We then investigated whether G119 mutations were associated with a fitness cost in <i>A. fumigatus.</i> These experiments showed a small but significant reduction in growth rate for strains with a G119V substitution, while strains with a G119C substitution did not exhibit a reduction in growth rate. These <i>in vitro</i> findings were confirmed in an <i>in vivo</i> pathogenicity model.
DOI: 10.6084/m9.figshare.19114469.v2
title: Resistance profiling of <i>Aspergillus fumigatus</i> to olorofim indicates absence of intrinsic resistance and unveils the molecular mechanisms of acquired olorofim resistance

description: Olorofim (F901318) is a new antifungal currently under clinical development that shows both <i>in vitro</i> and <i>in vivo</i> activity against a number of filamentous fungi including <i>Aspergillus fumigatus</i>. In this study, we screened <i>A. fumigatus</i> isolates for intrinsic olorofim-resistant <i>A. fumigatus</i> and evaluated the ability of <i>A. fumigatus</i> to acquire an olorofim-resistant phenotype. No intrinsic resistance was found in 975 clinical <i>A. fumigatus</i> isolates. However, we found that isolates with increased olorofim MICs (&gt; 8 mg/L) could be selected using a high number of conidia and olorofim exposure under laboratory conditions. Assessment of the frequency of acquired olorofim resistance development of <i>A. fumigatus</i> was shown to be higher than for voriconazole but lower than for itraconazole. Sequencing the <i>PyrE</i> gene of isogenic isolates with olorofim MICs of &gt;8 mg/L identified various amino acid substitutions with a hotspot at locus G119. Olorofim was shown to have reduced affinity to mutated target protein dihydroorotate dehydrogenase (DHODH) and the effect of these mutations was proven by introducing the mutations directly in <i>A. fumigatus</i>. We then investigated whether G119 mutations were associated with a fitness cost in <i>A. fumigatus.</i> These experiments showed a small but significant reduction in growth rate for strains with a G119V substitution, while strains with a G119C substitution did not exhibit a reduction in growth rate. These <i>in vitro</i> findings were confirmed in an <i>in vivo</i> pathogenicity model.
DOI: 10.6084/m9.figshare.18858199.v1
title: Methicillin-resistant <i>Staphylococcus aureus</i> in China: a multicenter longitudinal study and whole-genome sequencing

description: The aim of this study was to investigate the genomic epidemiology of MRSA in China to identify predominant linages and their associated genomic and phenotypic characteristic. In this study, we conducted whole-genome sequencing on 565 MRSA isolates from 7 provinces and municipalities of China between 2014 and 2020. MRSA isolates were subjected to MLST, <i>spa</i> typing, SCC<i>mec</i> typing, analysis of virulence determinants and antimicrobial susceptibility testing. Among 565 MRSA isolates tested, clonal complex (CC) 59 (31.2%), CC5 (23.4%) and CC8 (13.63%) were the major lineages, and the clonal structure was dominated by ST59-t437-IV (14.9%), ST239-t030-III (6.4%) and ST5-t2460-II (6.0%). Of note, CC8, the predominant lineage in 2014-2015, was replaced by CC59 after 2016. Interestingly, the extension and unstable structure of CC5 population was observed, with ST5-t311-II, ST764-t1084-II, ST5-t2460-II and ST764-t002-II existed complex competition. Further analysis revealed that virulence determinant profiles and antibiograms were closely associated with the clonal lineage. The CC59 MRSA were less resistant to most tested antimicrobials and carried fewer resistance determinants, while rifampicin resistance and mupirocin resistance was closely linked with CC8 and CC5, respectively. MRSA isolates conservatively carried multiple virulence genes involved in various functions. PVL encoding genes were markedly more common in ST338, CC30, CC398, ST8 and CC22, while <i>tsst</i>-1 was associated with ST5. In conclusion, the community-associated CC59-ST59-t437-IV lineage was found to be predominant in China, with diverse clonal isolates alternately circulating in various geographical locations. Our study highlights the need for MRSA surveillance in China in order to monitor changes in MRSA epidemiology.
DOI: 10.6084/m9.figshare.19085431
title: Emergence of colistin-resistant hypervirulent <i>Klebsiella pneumoniae</i> (CoR-HvKp) in China

description: Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant <i>Klebsiella pneumoniae</i> (CoRKp) are increasing. However, the molecular mechanism and relevance of colistin resistance and virulence remain unclear. Fourteen CoRKp strains were retrospectively screened from 1884 clinical <i>K. pneumoniae</i> isolates during 2017–2018 in China. Six CoRKp strains belonging to ST11 were MDR strains. Plasmid-mediated mobile colistin-resistance genes had a low prevalence in CoRKp. Our results revealed that up-regulated expression of two-component systems, especially <i>phoPQ,</i> contributed more to colistin resistance. <i>mgrB</i> mutation was the most common molecular mechanism of colistin resistance, caused by either nonsense mutations or insertion sequences, which drove the overexpression of <i>phoPQ system</i>. This study also identified three novel point mutations in <i>pmrAB</i> system, in which D313N mutation in <i>pmrB</i> was proved to increase the MIC to colistin by 16-fold. In addition, 6 out of 14 CoRKP strains independently carried hypervirulence genes. All six strains showed medium-to-high virulence phenotype compared with NTUH-K2044 strain in mice intraperitoneal challenge models. We found that 4 strains were biofilm strong producers and transcriptome analysis revealed that three of them significantly up-regulated expression of type III fimbrial shaft gene <i>mrkA</i>. In conclusion, our result revealed the emergence of colistin-resistant and hypervirulent MDR <i>K. pneumoniae,</i> which is a noticeable superbug and could cause a severe challenge to public health.
DOI: 10.6084/m9.figshare.19085431.v2
title: Emergence of colistin-resistant hypervirulent <i>Klebsiella pneumoniae</i> (CoR-HvKp) in China

description: Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant <i>Klebsiella pneumoniae</i> (CoRKp) are increasing. However, the molecular mechanism and relevance of colistin resistance and virulence remain unclear. Fourteen CoRKp strains were retrospectively screened from 1884 clinical <i>K. pneumoniae</i> isolates during 2017–2018 in China. Six CoRKp strains belonging to ST11 were MDR strains. Plasmid-mediated mobile colistin-resistance genes had a low prevalence in CoRKp. Our results revealed that up-regulated expression of two-component systems, especially <i>phoPQ,</i> contributed more to colistin resistance. <i>mgrB</i> mutation was the most common molecular mechanism of colistin resistance, caused by either nonsense mutations or insertion sequences, which drove the overexpression of <i>phoPQ system</i>. This study also identified three novel point mutations in <i>pmrAB</i> system, in which D313N mutation in <i>pmrB</i> was proved to increase the MIC to colistin by 16-fold. In addition, 6 out of 14 CoRKP strains independently carried hypervirulence genes. All six strains showed medium-to-high virulence phenotype compared with NTUH-K2044 strain in mice intraperitoneal challenge models. We found that 4 strains were biofilm strong producers and transcriptome analysis revealed that three of them significantly up-regulated expression of type III fimbrial shaft gene <i>mrkA</i>. In conclusion, our result revealed the emergence of colistin-resistant and hypervirulent MDR <i>K. pneumoniae,</i> which is a noticeable superbug and could cause a severe challenge to public health.
DOI: 10.6084/m9.figshare.17262731
title: Enhanced replication fitness of MERS-CoV clade B over clade A strains in camelids explains the dominance of clade B strains in the Arabian Peninsula

description: Middle East respiratory syndrome coronavirus (MERS-CoV) continues infecting humans and dromedary camels. While MERS-CoV strains from the Middle East region are subdivided into two clades (A and B), all the contemporary epidemic viruses belong to clade B. Thus, MERS-CoV clade B strains may display adaptive advantages over clade A in humans and/or reservoir hosts. To test this hypothesis <i>in vivo</i>, we compared an early epidemic clade A strain (EMC/2012) with a clade B strain (Jordan-1/2015) in an alpaca model monitoring virological and immunological parameters. Further, the Jordan-1/2015 strain has a partial amino acid (aa) deletion in the double-stranded (ds) RNA binding motif of the open reading frame ORF4a protein. Animals inoculated with the Jordan-1/2015 variant had higher MERS-CoV replicative capabilities in the respiratory tract and larger nasal viral shedding. In the nasal mucosa, the Jordan-1/2015 strain caused an early IFN response, suggesting a role for ORF4a as a moderate IFN antagonist <i>in vivo</i>. However, both strains elicited maximal transcription of antiviral interferon-stimulated genes (ISGs) at the peak of infection on 2 days post inoculation, correlating with subsequent decreases in tissular viral loads. Genome alignment analysis revealed several clade B-specific amino acid substitutions occurring in the replicase and the S proteins, which could explain a better adaptation of clade B strains in camelid hosts. Differences in replication and shedding reported herein indicate a better fitness and transmission capability of MERS-CoV clade B strains than their clade A counterparts.
DOI: 10.6084/m9.figshare.17262731.v2
title: Enhanced replication fitness of MERS-CoV clade B over clade A strains in camelids explains the dominance of clade B strains in the Arabian Peninsula

description: Middle East respiratory syndrome coronavirus (MERS-CoV) continues infecting humans and dromedary camels. While MERS-CoV strains from the Middle East region are subdivided into two clades (A and B), all the contemporary epidemic viruses belong to clade B. Thus, MERS-CoV clade B strains may display adaptive advantages over clade A in humans and/or reservoir hosts. To test this hypothesis <i>in vivo</i>, we compared an early epidemic clade A strain (EMC/2012) with a clade B strain (Jordan-1/2015) in an alpaca model monitoring virological and immunological parameters. Further, the Jordan-1/2015 strain has a partial amino acid (aa) deletion in the double-stranded (ds) RNA binding motif of the open reading frame ORF4a protein. Animals inoculated with the Jordan-1/2015 variant had higher MERS-CoV replicative capabilities in the respiratory tract and larger nasal viral shedding. In the nasal mucosa, the Jordan-1/2015 strain caused an early IFN response, suggesting a role for ORF4a as a moderate IFN antagonist <i>in vivo</i>. However, both strains elicited maximal transcription of antiviral interferon-stimulated genes (ISGs) at the peak of infection on 2 days post inoculation, correlating with subsequent decreases in tissular viral loads. Genome alignment analysis revealed several clade B-specific amino acid substitutions occurring in the replicase and the S proteins, which could explain a better adaptation of clade B strains in camelid hosts. Differences in replication and shedding reported herein indicate a better fitness and transmission capability of MERS-CoV clade B strains than their clade A counterparts.
DOI: 10.6084/m9.figshare.18743686
title: B cell receptor signatures associated with strong and poor SARS-CoV-2 vaccine responses

description: Breakthrough infection of SARS-CoV-2 is a serious challenge, as increased infections were documented in fully-vaccinated individuals. Recipients with poor antibody response are highly vulnerable to reinfection, whereas those with strong antibody responses achieve sterilizing immunity. Thus far, biomarkers associated with levels of vaccine-elicited antibody response are still lacking. Here, we studied the antibody response of age- and gender-controlled healthy cohort, who received inactivated SARS-CoV-2 vaccines and profiled the B cell receptor repertoires in longitudinally consecutive samples. Upon vaccination, all vaccinated individuals displayed a convergent antibody response with shared common antibody clones and public neutralizing antibodies. Strikingly, poor vaccine-responders are distinguishable from strong vaccine-responders by a biased V-usage before vaccination and IgG to IgM mRNA ratio. These findings reveal molecular signatures associated with the different levels of vaccine-induced antibody response, which could be further developed into biomarkers for the design of vaccination strategies.
DOI: 10.21233/y7s7-kx09
title: Lake Emily pollen dataset

description: Raw data for the Lake Emily pollen dataset submitted to the Neotoma Paleoecology Database. Data is available through the landing page in JSON format. The landing page referenced by the DOI also contains links to publications and a map-based viewer for the dataset. The Neotoma Paleoecology Database maintains a homepage at https://www.neotomadb.org.
DOI: 10.6084/m9.figshare.19076572
title: Possible recombination between two variants of concern in a COVID-19 patient

description: We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the <i>Orf1ab</i> and <i>Spike</i> genes was found.
DOI: 10.6084/m9.figshare.19076572.v1
title: Possible recombination between two variants of concern in a COVID-19 patient

description: We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the <i>Orf1ab</i> and <i>Spike</i> genes was found.