Thibault Rosazza, Chris Earl, Lukas Eigentler, Fordyce A. Davidson, Nicola R. Stanley-Wall
{"title":"Reciprocal sharing of extracellular proteases and extracellular matrix molecules facilitates Bacillus subtilis biofilm formation","authors":"Thibault Rosazza, Chris Earl, Lukas Eigentler, Fordyce A. Davidson, Nicola R. Stanley-Wall","doi":"10.1111/mmi.15288","DOIUrl":"https://doi.org/10.1111/mmi.15288","url":null,"abstract":"Extracellular proteases are a class of public good that support growth of <i>Bacillus subtilis</i> when nutrients are in a polymeric form. <i>Bacillus subtilis</i> biofilm matrix molecules are another class of public good that are needed for biofilm formation and are prone to exploitation. In this study, we investigated the role of extracellular proteases in <i>B. subtilis</i> biofilm formation and explored interactions between different public good producer strains across various conditions. We confirmed that extracellular proteases support biofilm formation even when glutamic acid provides a freely available nitrogen source. Removal of AprE from the NCIB 3610 secretome adversely affects colony biofilm architecture, while sole induction of WprA activity into an otherwise extracellular protease-free strain is sufficient to promote wrinkle development within the colony biofilm. We found that changing the nutrient source used to support growth affected <i>B. subtilis</i> biofilm structure, hydrophobicity and architecture. We propose that the different phenotypes observed may be due to increased protease dependency for growth when a polymorphic protein presents the sole nitrogen source. We however cannot exclude that the phenotypic changes are due to alternative matrix molecules being made. Co-culture of biofilm matrix and extracellular protease mutants can rescue biofilm structure, yet reliance on extracellular proteases for growth influences population coexistence dynamics. Our findings highlight the intricate interplay between these two classes of public goods, providing insights into microbial social dynamics during biofilm formation across different ecological niches.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"15 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Shen, Xin-Wei Song, David Bickel, Barry P. Rosen, Fang-Jie Zhao, Joris Messens, Jun Zhang
{"title":"Arsenate reductase of Rufibacter tibetensis is a metallophosphoesterase evolved to catalyze redox reactions","authors":"Jie Shen, Xin-Wei Song, David Bickel, Barry P. Rosen, Fang-Jie Zhao, Joris Messens, Jun Zhang","doi":"10.1111/mmi.15289","DOIUrl":"https://doi.org/10.1111/mmi.15289","url":null,"abstract":"An arsenate reductase (Car1) from the Bacteroidetes species <i>Rufibacter tibetensis</i> 1351<sup>T</sup> was isolated from the Tibetan Plateau. The strain exhibits resistance to arsenite [As(III)] and arsenate [As(V)] and reduces As(V) to As(III). Here we shed light on the mechanism of enzymatic reduction by Car1. AlphaFold2 structure prediction, active site energy minimization, and steady-state kinetics of wild-type and mutant enzymes give insight into the catalytic mechanism. Car1 is structurally related to calcineurin-like metallophosphoesterases (MPPs). It functions as a binuclear metal hydrolase with limited phosphatase activity, particularly relying on the divalent metal Ni<sup>2+</sup>. As an As(V) reductase, it displays metal promiscuity and is coupled to the thioredoxin redox cycle, requiring the participation of two cysteine residues, Cys74 and Cys76. These findings suggest that Car1 evolved from a common ancestor of extant phosphatases by incorporating a redox function into an existing MPP catalytic site. Its proposed mechanism of arsenate reduction involves Cys74 initiating a nucleophilic attack on arsenate, leading to the formation of a covalent intermediate. Next, a nucleophilic attack of Cys76 leads to the release of As(III) and the formation of a surface-exposed Cys74-Cys76 disulfide, ready for reduction by thioredoxin.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sokrich Ponndara, Mounia Kortebi, Frédéric Boccard, Stéphanie Bury-Moné, Virginia S. Lioy
{"title":"Principles of bacterial genome organization, a conformational point of view","authors":"Sokrich Ponndara, Mounia Kortebi, Frédéric Boccard, Stéphanie Bury-Moné, Virginia S. Lioy","doi":"10.1111/mmi.15290","DOIUrl":"https://doi.org/10.1111/mmi.15290","url":null,"abstract":"Bacterial chromosomes are large molecules that need to be highly compacted to fit inside the cells. Chromosome compaction must facilitate and maintain key biological processes such as gene expression and DNA transactions (replication, recombination, repair, and segregation). Chromosome and chromatin 3D-organization in bacteria has been a puzzle for decades. Chromosome conformation capture coupled to deep sequencing (Hi-C) in combination with other “omics” approaches has allowed dissection of the structural layers that shape bacterial chromosome organization, from DNA topology to global chromosome architecture. Here we review the latest findings using Hi-C and discuss the main features of bacterial genome folding.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"48 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bradyrhizobium japonicum HmuP is an RNA-binding protein that positively controls hmuR operon expression by suppression of a negative regulatory RNA element in the 5' untranslated region.","authors":"Peipei Wu, Alasteir Ong, Mark R O'Brian","doi":"10.1111/mmi.15274","DOIUrl":"10.1111/mmi.15274","url":null,"abstract":"<p><p>The hmuR operon encodes proteins for the uptake and utilization of heme as a nutritional iron source in Bradyrhizobium japonicum. The hmuR operon is transcriptionally activated by the Irr protein and is also positively controlled by HmuP by an unknown mechanism. An hmuP mutant does not express the hmuR operon genes nor does it grow on heme. Here, we show that hmuR expression from a heterologous promoter still requires hmuP, suggesting that HmuP does not regulate at the transcriptional level. Replacement of the 5' untranslated region (5'UTR) of an HmuP-independent gene with the hmuR 5'UTR conferred HmuP-dependent expression on that gene. Recombinant HmuP bound an HmuP-responsive RNA element (HPRE) within the hmuR 5'UTR. A 2 nt substitution predicted to destabilize the secondary structure of the HPRE abolished both HmuP binding activity in vitro and hmuR expression in cells. However, deletion of the HPRE partially restored hmuR expression in an hmuP mutant, and it rescued growth of the hmuP mutant on heme. These findings suggest that the HPRE is a negative regulatory RNA element that is suppressed when bound by HmuP to express the hmuR operon.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1217-1227"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edwin R Lampugnani, Kris Ford, Yin Ying Ho, Allison van de Meene, Jelle Lahnstein, Hwei-Ting Tan, Rachel A Burton, Geoffrey B Fincher, Thomas Shafee, Antony Bacic, Jochen Zimmer, Xiaohui Xing, Vincent Bulone, Monika S Doblin, Eric M Roberts
{"title":"Glycosyl transferase GT2 genes mediate the biosynthesis of an unusual (1,3;1,4)-β-glucan exopolysaccharide in the bacterium Sarcina ventriculi.","authors":"Edwin R Lampugnani, Kris Ford, Yin Ying Ho, Allison van de Meene, Jelle Lahnstein, Hwei-Ting Tan, Rachel A Burton, Geoffrey B Fincher, Thomas Shafee, Antony Bacic, Jochen Zimmer, Xiaohui Xing, Vincent Bulone, Monika S Doblin, Eric M Roberts","doi":"10.1111/mmi.15276","DOIUrl":"10.1111/mmi.15276","url":null,"abstract":"<p><p>Linear, unbranched (1,3;1,4)-β-glucans (mixed-linkage glucans or MLGs) are commonly found in the cell walls of grasses, but have also been detected in basal land plants, algae, fungi and bacteria. Here we show that two family GT2 glycosyltransferases from the Gram-positive bacterium Sarcina ventriculi are capable of synthesizing MLGs. Immunotransmission electron microscopy demonstrates that MLG is secreted as an exopolysaccharide, where it may play a role in organizing individual cells into packets that are characteristic of Sarcina species. Heterologous expression of these two genes shows that they are capable of producing MLGs in planta, including an MLG that is chemically identical to the MLG secreted from S. ventriculi cells but which has regularly spaced (1,3)-β-linkages in a structure not reported previously for MLGs. The tandemly arranged, paralogous pair of genes are designated SvBmlgs1 and SvBmlgs2. The data indicate that MLG synthases have evolved different enzymic mechanisms for the incorporation of (1,3)-β- and (1,4)-β-glucosyl residues into a single polysaccharide chain. Amino acid variants associated with the evolutionary switch from (1,4)-β-glucan (cellulose) to MLG synthesis have been identified in the active site regions of the enzymes. The presence of MLG synthesis in bacteria could prove valuable for large-scale production of MLG for medical, food and beverage applications.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1245-1261"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Corinne Asencio, Perrine Hervé, Pauline Morand, Quentin Oliveres, Chloé Alexandra Morel, Valérie Prouzet-Mauleon, Marc Biran, Sarah Monic, Mélanie Bonhivers, Derrick Roy Robinson, Marc Ouellette, Loïc Rivière, Frédéric Bringaud, Emmanuel Tetaud
{"title":"Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing in Trypanosoma and Leishmania.","authors":"Corinne Asencio, Perrine Hervé, Pauline Morand, Quentin Oliveres, Chloé Alexandra Morel, Valérie Prouzet-Mauleon, Marc Biran, Sarah Monic, Mélanie Bonhivers, Derrick Roy Robinson, Marc Ouellette, Loïc Rivière, Frédéric Bringaud, Emmanuel Tetaud","doi":"10.1111/mmi.15256","DOIUrl":"10.1111/mmi.15256","url":null,"abstract":"<p><p>Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and various forms of leishmaniasis (Leishmania spp.), as well as several animal diseases with important economic impact (African trypanosomes, including Trypanosoma congolense). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinant Streptococcus pyogenes Cas9 (SpCas9) and an in vitro-synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete, and mutate candidate genes in various stages of the life cycle of T. brucei and T. congolense, and Leishmania promastigotes. The functionality of SpCas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics but requires only cloning and PCR screening of the clones. Importantly, this approach is adaptable to any wild-type parasite.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1079-1094"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John K Barrows, Kamya A Stubbs, Irina F Padilla-Montoya, Thomas C Leeper, Michael W Van Dyke
{"title":"Manganese-dependent transcription regulation by MntR and PerR in Thermus thermophilus HB8.","authors":"John K Barrows, Kamya A Stubbs, Irina F Padilla-Montoya, Thomas C Leeper, Michael W Van Dyke","doi":"10.1111/mmi.15278","DOIUrl":"10.1111/mmi.15278","url":null,"abstract":"<p><p>Bacteria contain conserved mechanisms to control the intracellular levels of metal ions. Metalloregulatory transcription factors bind metal cations and play a central role in regulating gene expression of metal transporters. Often, these transcription factors regulate transcription by binding to a specific DNA sequence in the promoter region of target genes. Understanding the preferred DNA-binding sequence for transcriptional regulators can help uncover novel gene targets and provide insight into the biological role of the transcription factor in the host organism. Here, we identify consensus DNA-binding sequences and subsequent transcription regulatory networks for two metalloregulators from the ferric uptake regulator (FUR) and diphtheria toxin repressor (DtxR) superfamilies in Thermus thermophilus HB8. By homology search, we classify the DtxR homolog as a manganese-specific, MntR (TtMntR), and the FUR homolog as a peroxide-sensing, PerR (TtPerR). Both transcription factors repress separate ZIP transporter genes in vivo, and TtPerR acts as a bifunctional transcription regulator by activating the expression of ferric and hemin transport systems. We show TtPerR and TtMntR bind DNA in the presence of manganese in vitro and in vivo; however, TtPerR is unable to bind DNA in the presence of iron, likely due to iron-mediated histidine oxidation. Unlike canonical PerR homologs, TtPerR does not appear to contribute to peroxide detoxification. Instead, the TtPerR regulon and DNA binding sequence are more reminiscent of Fur or Mur homologs. Collectively, these results highlight the similarities and differences between two metalloregulatory superfamilies and underscore the interplay of manganese and iron in transcription factor regulation.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1228-1244"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tristan A Nowak, Russell L Burke, Maria A Diuk-Wasser, Yi-Pin Lin
{"title":"Lizards and the enzootic cycle of Borrelia burgdorferi sensu lato.","authors":"Tristan A Nowak, Russell L Burke, Maria A Diuk-Wasser, Yi-Pin Lin","doi":"10.1111/mmi.15271","DOIUrl":"10.1111/mmi.15271","url":null,"abstract":"<p><p>Emerging and re-emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard-tick-Borrelia interactions and highlights the importance of an eco-immunology lens for zoonotic pathogen transmission studies.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1262-1272"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikkel M. Liljegren, João A. Gama, Pål J. Johnsen, Klaus Harms
{"title":"The recombination initiation functions DprA and RecFOR suppress microindel mutations in Acinetobacter baylyi ADP1","authors":"Mikkel M. Liljegren, João A. Gama, Pål J. Johnsen, Klaus Harms","doi":"10.1111/mmi.15277","DOIUrl":"https://doi.org/10.1111/mmi.15277","url":null,"abstract":"Short-Patch Double Illegitimate Recombination (SPDIR) has been recently identified as a rare mutation mechanism. During SPDIR, ectopic DNA single-strands anneal with genomic DNA at microhomologies and get integrated during DNA replication, presumably acting as primers for Okazaki fragments. The resulting microindel mutations are highly variable in size and sequence. In the soil bacterium <i>Acinetobacter baylyi</i>, SPDIR is tightly controlled by genome maintenance functions including RecA. It is thought that RecA scavenges DNA single-strands and renders them unable to anneal. To further elucidate the role of RecA in this process, we investigate the roles of the upstream functions DprA, RecFOR, and RecBCD, all of which load DNA single-strands with RecA. Here we show that all three functions suppress SPDIR mutations in the wildtype to levels below the detection limit. While SPDIR mutations are slightly elevated in the absence of DprA, they are strongly increased in the absence of both DprA and RecA. This SPDIR-avoiding function of DprA is not related to its role in natural transformation. These results suggest a function for DprA in combination with RecA to avoid potentially harmful microindel mutations, and offer an explanation for the ubiquity of <i>dprA</i> in the genomes of naturally non-transformable bacteria.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kevin Debatisse, Pierre Lopez, Maryse Poli, Philippe Rousseau, Manuel Campos, Michèle Coddeville, Muriel Cocaign‐Bousquet, Pascal Le Bourgeois
{"title":"Redefining the bacteriophage mv4 site‐specific recombination system and the sequence specificity of its attB and core‐attP sites","authors":"Kevin Debatisse, Pierre Lopez, Maryse Poli, Philippe Rousseau, Manuel Campos, Michèle Coddeville, Muriel Cocaign‐Bousquet, Pascal Le Bourgeois","doi":"10.1111/mmi.15275","DOIUrl":"https://doi.org/10.1111/mmi.15275","url":null,"abstract":"Through their involvement in the integration and excision of a large number of mobile genetic elements, such as phages and integrative and conjugative elements (ICEs), site‐specific recombination systems based on heterobivalent tyrosine recombinases play a major role in genome dynamics and evolution. However, despite hundreds of these systems having been identified in genome databases, very few have been described in detail, with none from phages that infect <jats:italic>Bacillota</jats:italic> (formerly <jats:italic>Firmicutes</jats:italic>). In this study, we reanalyzed the recombination module of <jats:italic>Lactobacillus delbrueckii</jats:italic> subsp. <jats:italic>bulgaricus</jats:italic> phage mv4, previously considered atypical compared with classical systems. Our results reveal that mv4 integrase is a 369 aa protein with all the structural hallmarks of recombinases from the Tn<jats:italic>916</jats:italic> family and that it cooperatively interacts with its recombination sites. Using randomized DNA libraries, NGS sequencing, and other molecular approaches, we show that the 21‐bp core‐<jats:italic>attP</jats:italic> and <jats:italic>attB</jats:italic> sites have structural similarities to classical systems only if considering the nucleotide degeneracy, with two 7‐bp inverted regions corresponding to <jats:sup>mv4</jats:sup>Int core‐binding sites surrounding a 7‐bp strand‐exchange region. We also examined the different compositional constraints in the core‐binding regions, which define the sequence space of permissible recombination sites.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"161 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}