mLife最新文献

{"title":"Metabolic activities of marine ammonia-oxidizing archaea orchestrated by quorum sensing.","authors":"Olivier Pereira, Wei Qin, Pierre E Galand, Didier Debroas, Raphael Lami, Corentin Hochart, Yangkai Zhou, Jin Zhou, Chuanlun Zhang","doi":"10.1002/mlf2.12144","DOIUrl":"10.1002/mlf2.12144","url":null,"abstract":"<p><p>Ammonia-oxidizing archaea (AOA) play crucial roles in marine carbon and nitrogen cycles by fixing inorganic carbon and performing the initial step of nitrification. Evaluation of carbon and nitrogen metabolism popularly relies on functional genes such as <i>amoA</i> and <i>accA</i>. Increasing studies suggest that quorum sensing (QS) mainly studied in biofilms for bacteria may serve as a universal communication and regulatory mechanism among prokaryotes; however, this has yet to be demonstrated in marine planktonic archaea. To bridge this knowledge gap, we employed a combination of metabolic activity markers (<i>amoA</i>, <i>accA</i>, and <i>grs</i>) to elucidate the regulation of AOA-mediated nitrogen, carbon processes, and their interactions with the surrounding heterotrophic population. Through co-transcription investigations linking metabolic markers to potential key QS genes, we discovered that QS molecules could regulate AOA's carbon, nitrogen, and lipid metabolisms under different conditions. Interestingly, specific AOA ecotypes showed a preference for employing distinct QS systems and a distinct QS circuit involving a typical population. Overall, our data demonstrate that QS orchestrates nitrogen and carbon metabolism, including the exchange of organic metabolites between AOA and surrounding heterotrophic bacteria, which has been previously overlooked in marine AOA research.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"417-429"},"PeriodicalIF":4.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EmbB and EmbC regulate the sensitivity of <i>Mycobacterium abscessus</i> to echinomycin.","authors":"Jing He, Yamin Gao, Jingyun Wang, H M Adnan Hameed, Shuai Wang, Cuiting Fang, Xirong Tian, Jingran Zhang, Xingli Han, Yanan Ju, Yaoju Tan, Junying Ma, Jianhua Ju, Jinxing Hu, Jianxiong Liu, Tianyu Zhang","doi":"10.1002/mlf2.12139","DOIUrl":"10.1002/mlf2.12139","url":null,"abstract":"<p><p>Treatment of <i>Mycobacterium abscessus</i> (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti-Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH). ECH showed activity against Mab at a minimum inhibitory concentration (MIC) of 2 µg/ml. A ΔembC strain in which the <i>embC</i> gene was knocked out showed hypersensitivity to ECH (MIC: 0.0078-0.0156 µg/ml). The MICs of ECH-resistant strains screened with reference to ΔembC ranged from 0.25 to 1 µg/ml. Mutations in EmbB, including D306A, D306N, R350G, V555I, and G581S, increased the Mab's resistance to ECH when overexpressed in ΔembC individually (MIC: 0.25-0.5 µg/ml). These EmbB mutants, edited using the CRISPR/Cpf1 system, showed heightened resistance to ECH (MIC: 0.25-0.5 µg/ml). The permeability of these Mab strains with edited genes and overexpression was reduced, as evidenced by an ethidium bromide accumulation assay, but it remained significantly higher than that of the parent Mab. In summary, our study demonstrates that ECH exerts potent anti-Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH. Mutation in EmbB may partially compensate for a loss of EmbC function.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"459-470"},"PeriodicalIF":4.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Staphylococcus aureus</i> SOS response: Activation, impact, and drug targets.","authors":"Kaiying Cheng, Yukang Sun, Huan Yu, Yingxuan Hu, Yini He, Yuanyuan Shen","doi":"10.1002/mlf2.12137","DOIUrl":"10.1002/mlf2.12137","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is a common cause of diverse infections, ranging from superficial to invasive, affecting both humans and animals. The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants. This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments. The bacterial Save Our Souls (SOS) response, triggered by genotoxic stressors, encompasses host immune defenses and antibiotics, playing a crucial role in bacterial survival, invasiveness, virulence, and drug resistance. Accumulating evidence underscores the pivotal role of the SOS response system in the pathogenicity of <i>S. aureus</i>. Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial resistance. Here, we provide a comprehensive review of the activation, impact, and key proteins associated with the SOS response in <i>S. aureus</i>. Additionally, perspectives on therapeutic strategies targeting the SOS response for <i>S. aureus</i>, both individually and in combination with traditional antibiotics are proposed.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"343-366"},"PeriodicalIF":4.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc finger 4 negatively controls the transcriptional activator Fzf1 in <i>Saccharomyces cerevisiae</i>.","authors":"Ying Du, Chaoqun Ma, Stanley A Moore, Wei Xiao","doi":"10.1002/mlf2.12141","DOIUrl":"10.1002/mlf2.12141","url":null,"abstract":"<p><p>Fzf1 is a <i>Saccharomyces cerevisiae</i> transcription factor containing five zinc fingers (ZFs). It regulates the expression of at least five downstream genes, including <i>SSU1</i>, <i>YHB1</i>, <i>DDI2/</i>3, and <i>YNR064c</i>, by recognizing a consensus sequence, CS2, found in these gene promoters. These gene products are involved in cellular responses to various chemical stresses. For example, <i>SSU1</i> encodes a sodium sulfite efflux protein that confers sulfite resistance. However, the underlying molecular mechanism through which Fzf1 responds to chemical stress and coordinates target gene activation remains elusive. Interestingly, several mutations in the fourth ZF (ZF4) of Fzf1 have previously been reported to confer either sulfite resistance or elevated basal-level expression of <i>YHB1</i>, indicating that ZF4 negatively impacts Fzf1 activity. Since ZF4 is dispensable for CS2 binding in vitro, we hypothesized that ZF4 is a negative regulator of Fzf1 and that chemically induced Fzf1-regulated gene expression occurs via de-repression. All five genes examined were cross-induced by corresponding chemicals in an Fzf1-dependent manner, and all three ZF4 mutations and a ZF4 deletion conferred increased basal-level expression and <i>SSU1</i>-dependent sulfite resistance. A ZF4 deletion did not alter the target DNA binding, consistent with the observed codominant phenotype. These observations collectively reveal that Fzf1 remains inactive by default at the target promoters and that its activation is at least partially achieved by self-derepression through chemical modification and/or a conformational change.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"391-402"},"PeriodicalIF":4.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient, compact, and versatile: Type I-F2 CRISPR-Cas system.","authors":"Shengsheng Ma, Senfeng Zhang, Kunming Liu, Tao Hu, Chunyi Hu","doi":"10.1002/mlf2.12145","DOIUrl":"10.1002/mlf2.12145","url":null,"abstract":"","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"384-386"},"PeriodicalIF":4.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The phytopathogen <i>Xanthomonas campestris</i> senses and effluxes salicylic acid via a sensor HepR and an RND family efflux pump to promote virulence in host plants.","authors":"Kai Song, Ruifang Li, Ying Cui, Bo Chen, Lian Zhou, Wenying Han, Bo-Le Jiang, Ya-Wen He","doi":"10.1002/mlf2.12140","DOIUrl":"10.1002/mlf2.12140","url":null,"abstract":"<p><p>Salicylic acid (SA) plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens. Following pathogen recognition, SA biosynthesis dramatically increases at the infection site of the host plant. The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood. The objective of this work was to determine how the model phytopathogen <i>Xanthomonas campestris</i> pv. <i>campestris</i> (Xcc) senses and effluxes SA during infection inside host plants. First, RNA-Seq analysis identified an SA-responsive operon Xcc4167-Xcc4171, encoding a MarR family transcription factor HepR and an RND (resistance-nodulation-cell division) family efflux pump HepABCD in Xcc. Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR negatively regulated <i>hepABCD</i> expression by specifically binding to an AT-rich region of the promoter of the <i>hepRABCD</i> operon, P_hep. Second, isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor. SA binding released HepR from its cognate promoter P_hep and then induced the expression of <i>hepABCD</i>. Third, the RND family efflux pump HepABCD was responsible for SA efflux. The <i>hepRABCD</i> cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover. Finally, the <i>hepRABCD</i> cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage. These findings suggest that the ability of Xcc to co-opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"430-444"},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perchlorate-tolerant bacterial strains isolated from the Mars-analog Qaidam Basin soils exposed to Earth's near space.","authors":"Li Liu, Mengling Kang, Zhe Wang, Jianxun Shen, Yongxin Pan, Wei Lin","doi":"10.1002/mlf2.12142","DOIUrl":"10.1002/mlf2.12142","url":null,"abstract":"<p><p>Earth's lower near space of 20-40 km above sea level with polyextreme conditions serves as a unique Mars analog for astrobiological research to investigate the limits of life on Earth and planetary protection considerations for Mars exploration. In this study, we exposed Mars-like desert regolith to near space at a float altitude of ~35 km and isolated four bacterial strains after exposure. In addition to stress tolerance to extreme environmental stressors, these strains represent a remarkable tolerance to perchlorate that is widespread in present-day Martian soils. These extremophilic bacterial strains screened through near-space exposure could serve as promising candidates for future astrobiological research in space stations or in laboratory-based planetary simulation environments.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"471-475"},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral microbiome in human health and diseases.","authors":"Siqi Tian, Tao Ding, Hui Li","doi":"10.1002/mlf2.12136","DOIUrl":"10.1002/mlf2.12136","url":null,"abstract":"<p><p>The oral cavity contains the second-largest microbiota in the human body. The cavity's anatomically and physiologically diverse niches facilitate a wide range of symbiotic bacteria living at distinct oral sites. Consequently, the oral microbiota exhibits site specificity, with diverse species, compositions, and structures influenced by specific aspects of their placement. Variations in oral microbiota structure caused by changes in these influencing factors can impact overall health and lead to the development of diseases-not only in the oral cavity but also in organs distal to the mouth-such as cancer, cardiovascular disease, and respiratory disease. Conversely, diseases can exacerbate the imbalance of the oral microbiota, creating a vicious cycle. Understanding the heterogeneity of both the oral microbiome and individual humans is important for investigating the causal links between the oral microbiome and diseases. Additionally, understanding the intricacies of the oral microbiome's composition and regulatory factors will help identify the potential causes of related diseases and develop interventions to prevent and treat illnesses in this domain. Therefore, turning to the extant research in this field, we systematically review the relationship between oral microbiome dynamics and human diseases.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"367-383"},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of β-nitrostyrene derivatives as potential quorum sensing inhibitors for biofilm inhibition and antivirulence factor therapeutics against <i>Serratia marcescens</i>.","authors":"Jiang Wang, Jingyi Yang, Pradeepraj Durairaj, Wei Wang, Dongyan Wei, Shi Tang, Haiqing Liu, Dayong Wang, Ai-Qun Jia","doi":"10.1002/mlf2.12135","DOIUrl":"10.1002/mlf2.12135","url":null,"abstract":"<p><p>Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug-resistant pathogens. In this study, we designed and synthesized a total of 33 β-nitrostyrene derivatives using 1-nitro-2-phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen <i>Serratia marcescens</i>. The QS-inhibitory effects of these compounds were evaluated using <i>S. marcescens</i> NJ01 and the reporter strain <i>Chromobacterium violaceum</i> CV026. Among the 33 new β-nitrostyrene derivatives, (<i>E</i>)-1-methyl-4-(2-nitrovinyl)benzene (m-NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of <i>S. marcescens</i> NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m-NPe (50 μg/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m-NPe (50 μg/ml) decreased virulence factors in <i>S. marcescens</i> NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In <i>S. marcescens</i> 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS- and biofilm-related genes (<i>flhD, fimA, fimC, sodB, bsmB, pigA, pigC</i>, and <i>shlA</i>) were downregulated by 1.21- to 2.32-fold. Molecular dynamics analysis showed that m-NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1 M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against <i>S. marcescens</i>. Overall, this study highlights the efficacy of m-NPe in suppressing the virulence factors of <i>S. marcescens</i>, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"445-458"},"PeriodicalIF":4.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalytically active prokaryotic Argonautes employ phospholipase D family proteins to strengthen immunity against different genetic invaders.","authors":"Feiyue Cheng, Aici Wu, Zhihua Li, Jing Xu, Xifeng Cao, Haiying Yu, Zhenquan Liu, Rui Wang, Wenyuan Han, Hua Xiang, Ming Li","doi":"10.1002/mlf2.12138","DOIUrl":"10.1002/mlf2.12138","url":null,"abstract":"<p><p>Prokaryotic Argonautes (pAgos) provide bacteria and archaea with immunity against plasmids and viruses. Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids, while inactive pAgos lacking catalytic residues employ auxiliary effectors, such as nonspecific nucleases, to trigger abortive infection upon detection of foreign nucleic acids. Here, we report a unique group of catalytically active pAgo proteins that frequently associate with a phospholipase D (PLD) family protein. We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA, while interestingly, its immunity against a single-stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein. We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes. Moreover, the pAgo protein alone enhances gene editing, which is unexpectedly inhibited by the PLD protein. Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"3 3","pages":"403-416"},"PeriodicalIF":4.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}