Molecular Microbiology最新文献

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Stearoyl-CoA desaturase regulates organelle biogenesis and hepatic merozoite formation in Plasmodium berghei. 硬脂酰-CoA 去饱和酶调控疟原虫细胞器的生物发生和肝丝虫的形成
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-02-28 DOI: 10.1111/mmi.15246
Sunil Kumar Narwal, Akancha Mishra, Raksha Devi, Ankit Ghosh, Hadi Hasan Choudhary, Satish Mishra
{"title":"Stearoyl-CoA desaturase regulates organelle biogenesis and hepatic merozoite formation in Plasmodium berghei.","authors":"Sunil Kumar Narwal, Akancha Mishra, Raksha Devi, Ankit Ghosh, Hadi Hasan Choudhary, Satish Mishra","doi":"10.1111/mmi.15246","DOIUrl":"10.1111/mmi.15246","url":null,"abstract":"<p><p>Plasmodium is an obligate intracellular parasite that requires intense lipid synthesis for membrane biogenesis and survival. One of the principal membrane components is oleic acid, which is needed to maintain the membrane's biophysical properties and fluidity. The malaria parasite can modify fatty acids, and stearoyl-CoA Δ9-desaturase (Scd) is an enzyme that catalyzes the synthesis of oleic acid by desaturation of stearic acid. Scd is dispensable in P. falciparum blood stages; however, its role in mosquito and liver stages remains unknown. We show that P. berghei Scd localizes to the ER in the blood and liver stages. Disruption of Scd in the rodent malaria parasite P. berghei did not affect parasite blood stage propagation, mosquito stage development, or early liver-stage development. However, when Scd KO sporozoites were inoculated intravenously or by mosquito bite into mice, they failed to initiate blood-stage infection. Immunofluorescence analysis revealed that organelle biogenesis was impaired and merozoite formation was abolished, which initiates blood-stage infections. Genetic complementation of the KO parasites restored merozoite formation to a level similar to that of WT parasites. Mice immunized with Scd KO sporozoites confer long-lasting sterile protection against infectious sporozoite challenge. Thus, the Scd KO parasite is an appealing candidate for inducing protective pre-erythrocytic immunity and hence its utility as a GAP.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990715","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}
引用次数: 0
Live to fight another day: The bacterial nucleoid under stress 为新的一天而战压力下的细菌核仁
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 DOI: 10.1111/mmi.15272
Azra M. Walker, Elio A. Abbondanzieri, Anne S. Meyer
{"title":"Live to fight another day: The bacterial nucleoid under stress","authors":"Azra M. Walker, Elio A. Abbondanzieri, Anne S. Meyer","doi":"10.1111/mmi.15272","DOIUrl":"https://doi.org/10.1111/mmi.15272","url":null,"abstract":"The bacterial chromosome is both highly supercoiled and bound by an ensemble of proteins and RNA, causing the DNA to form a compact structure termed the nucleoid. The nucleoid serves to condense, protect, and control access to the bacterial chromosome through a variety of mechanisms that remain incompletely understood. The nucleoid is also a dynamic structure, able to change both in size and composition. The dynamic nature of the bacterial nucleoid is particularly apparent when studying the effects of various stresses on bacteria, which require cells to protect their DNA and alter patterns of transcription. Stresses can lead to large changes in the organization and composition of the nucleoid on timescales as short as a few minutes. Here, we summarize some of the recent advances in our understanding of how stress can alter the organization of bacterial chromosomes.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817465","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}
引用次数: 0
Regulation of late-acting operons by three transcription factors and a CRISPR-Cas component during Myxococcus xanthus development. 黄肉球菌发育过程中三个转录因子和一个 CRISPR-Cas 组件对晚期作用操作子的调控。
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-03-25 DOI: 10.1111/mmi.15252
Shreya Saha, Lee Kroos
{"title":"Regulation of late-acting operons by three transcription factors and a CRISPR-Cas component during Myxococcus xanthus development.","authors":"Shreya Saha, Lee Kroos","doi":"10.1111/mmi.15252","DOIUrl":"10.1111/mmi.15252","url":null,"abstract":"<p><p>Upon starvation, rod-shaped Myxococcus xanthus bacteria form mounds and then differentiate into round, stress-resistant spores. Little is known about the regulation of late-acting operons important for spore formation. C-signaling has been proposed to activate FruA, which binds DNA cooperatively with MrpC to stimulate transcription of developmental genes. We report that this model can explain regulation of the fadIJ operon involved in spore metabolism, but not that of the spore coat biogenesis operons exoA-I, exoL-P, and nfsA-H. Rather, a mutation in fruA increased the transcript levels from these operons early in development, suggesting negative regulation by FruA, and a mutation in mrpC affected transcript levels from each operon differently. FruA bound to all four promoter regions in vitro, but strikingly each promoter region was unique in terms of whether or not MrpC and/or the DNA-binding domain of Nla6 bound, and in terms of cooperative binding. Furthermore, the DevI component of a CRISPR-Cas system is a negative regulator of all four operons, based on transcript measurements. Our results demonstrate complex regulation of sporulation genes by three transcription factors and a CRISPR-Cas component, which we propose produces spores suited to withstand starvation and environmental insults.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207297","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}
引用次数: 0
The galactose metabolism genes UGE1 and UGM1 are novel virulence factors of the maize anthracnose fungus Colletotrichum graminicola. 半乳糖代谢基因 UGE1 和 UGM1 是玉米炭疽病菌 Colletotrichum graminicola 的新型毒力因子。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-02-23 DOI: 10.1111/mmi.15242
Maximilian Groß, Beate Dika, Elisabeth Loos, Lala Aliyeva-Schnorr, Holger B Deising
{"title":"The galactose metabolism genes UGE1 and UGM1 are novel virulence factors of the maize anthracnose fungus Colletotrichum graminicola.","authors":"Maximilian Groß, Beate Dika, Elisabeth Loos, Lala Aliyeva-Schnorr, Holger B Deising","doi":"10.1111/mmi.15242","DOIUrl":"10.1111/mmi.15242","url":null,"abstract":"<p><p>Fungal cell walls represent the frontline contact with the host and play a prime role in pathogenesis. While the roles of the cell wall polymers like chitin and branched β-glucan are well understood in vegetative and pathogenic development, that of the most prominent galactose-containing polymers galactosaminogalactan and fungal-type galactomannan is unknown in plant pathogenic fungi. Mining the genome of the maize pathogen Colletotrichum graminicola identified the single-copy key galactose metabolism genes UGE1 and UGM1, encoding a UDP-glucose-4-epimerase and UDP-galactopyranose mutase, respectively. UGE1 is thought to be required for biosynthesis of both polymers, whereas UGM1 is specifically required for fungal-type galactomannan formation. Promoter:eGFP fusion strains revealed that both genes are expressed in vegetative and in pathogenic hyphae at all stages of pathogenesis. Targeted deletion of UGE1 and UGM1, and fluorescence-labeling of galactosaminogalactan and fungal-type galactomannan confirmed that Δuge1 mutants were unable to synthesize either of these polymers, and Δugm1 mutants did not exhibit fungal-type galactomannan. Appressoria of Δuge1, but not of Δugm1 mutants, were defective in adhesion, highlighting a function of galactosaminogalactan in the establishment of these infection cells on hydrophobic surfaces. Both Δuge1 and Δugm1 mutants showed cell wall defects in older vegetative hyphae and severely reduced appressorial penetration competence. On intact leaves of Zea mays, both mutants showed strongly reduced disease symptom severity, indicating that UGE1 and UGM1 represent novel virulence factors of C. graminicola.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940317","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}
引用次数: 0
The swimming defect caused by the absence of the transcriptional regulator LdtR in Sinorhizobium meliloti is restored by mutations in the motility genes motA and motS. 通过对运动基因 motA 和 motS 进行突变,可以恢复瓜叶镰刀菌因缺少转录调节因子 LdtR 而导致的游动缺陷。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-03-08 DOI: 10.1111/mmi.15247
Richard C Sobe, Birgit E Scharf
{"title":"The swimming defect caused by the absence of the transcriptional regulator LdtR in Sinorhizobium meliloti is restored by mutations in the motility genes motA and motS.","authors":"Richard C Sobe, Birgit E Scharf","doi":"10.1111/mmi.15247","DOIUrl":"10.1111/mmi.15247","url":null,"abstract":"<p><p>The flagellar motor is a powerful macromolecular machine used to propel bacteria through various environments. We determined that flagellar motility of the alpha-proteobacterium Sinorhizobium meliloti is nearly abolished in the absence of the transcriptional regulator LdtR, known to influence peptidoglycan remodeling and stress response. LdtR does not regulate motility gene transcription. Remarkably, the motility defects of the ΔldtR mutant can be restored by secondary mutations in the motility gene motA or a previously uncharacterized gene in the flagellar regulon, which we named motS. MotS is not essential for S. meliloti motility and may serve an accessory role in flagellar motor function. Structural modeling predicts that MotS comprised an N-terminal transmembrane segment, a long-disordered region, and a conserved β-sandwich domain. The C terminus of MotS is localized in the periplasm. Genetics based substitution of MotA with MotA<sub>G12S</sub> also restored the ΔldtR motility defect. The MotA<sub>G12S</sub> variant protein features a local polarity shift at the periphery of the MotAB stator units. We propose that MotS may be required for optimal alignment of stators in wild-type flagellar motors but becomes detrimental in cells with altered peptidoglycan. Similarly, the polarity shift in stator units composed of MotB/MotA<sub>G12S</sub> might stabilize its interaction with altered peptidoglycan.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065578","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}
引用次数: 0
A long journey to the colon: The role of the small intestine microbiota in intestinal disease 通往结肠的漫长旅程小肠微生物群在肠道疾病中的作用
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 DOI: 10.1111/mmi.15270
Nicolas G. Shealy, Madi Baltagulov, Mariana X. Byndloss
{"title":"A long journey to the colon: The role of the small intestine microbiota in intestinal disease","authors":"Nicolas G. Shealy, Madi Baltagulov, Mariana X. Byndloss","doi":"10.1111/mmi.15270","DOIUrl":"https://doi.org/10.1111/mmi.15270","url":null,"abstract":"The small intestine represents a complex and understudied gut niche with significant implications for human health. Indeed, many infectious and non-infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non-invasive diagnosis and treatment. One major neglected aspect of small intestinal diseases is the feedback relationship with the resident collection of commensal organisms, the gut microbiota. Studies focused on microbiota–host interactions in the small intestine in the context of infectious and non-infectious diseases are required to identify potential therapeutic targets dissimilar from those used for large bowel diseases. While sparsely populated, the small intestine represents a stringent commensal bacterial microenvironment the host relies upon for nutrient acquisition and protection against invading pathogens (colonization resistance). Indeed, recent evidence suggests that disruptions to host–microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non-infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non-infectious diseases of the gastrointestinal (GI) tract. We also discuss gaps in knowledge on the role of commensal microorganisms in proximal GI tract function during health and disease.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817356","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}
引用次数: 0
Tetraether archaeal lipids promote long-term survival in extreme conditions. 四醚古菌脂质可促进在极端条件下的长期生存。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-02-19 DOI: 10.1111/mmi.15240
Geraldy Lie Stefanus Liman, Andy A Garcia, Kristin A Fluke, Hayden R Anderson, Sarah C Davidson, Paula V Welander, Thomas J Santangelo
{"title":"Tetraether archaeal lipids promote long-term survival in extreme conditions.","authors":"Geraldy Lie Stefanus Liman, Andy A Garcia, Kristin A Fluke, Hayden R Anderson, Sarah C Davidson, Paula V Welander, Thomas J Santangelo","doi":"10.1111/mmi.15240","DOIUrl":"10.1111/mmi.15240","url":null,"abstract":"<p><p>The sole unifying feature of the incredibly diverse Archaea is their isoprenoid-based ether-linked lipid membranes. Unique lipid membrane composition, including an abundance of membrane-spanning tetraether lipids, impart resistance to extreme conditions. Many questions remain, however, regarding the synthesis and modification of tetraether lipids and how dynamic changes to archaeal lipid membrane composition support hyperthermophily. Tetraether membranes, termed glycerol dibiphytanyl glycerol tetraethers (GDGTs), are generated by tetraether synthase (Tes) by joining the tails of two bilayer lipids known as archaeol. GDGTs are often further specialized through the addition of cyclopentane rings by GDGT ring synthase (Grs). A positive correlation between relative GDGT abundance and entry into stationary phase growth has been observed, but the physiological impact of inhibiting GDGT synthesis has not previously been reported. Here, we demonstrate that the model hyperthermophile Thermococcus kodakarensis remains viable when Tes (TK2145) or Grs (TK0167) are deleted, permitting phenotypic and lipid analyses at different temperatures. The absence of cyclopentane rings in GDGTs does not impact growth in T. kodakarensis, but an overabundance of rings due to ectopic Grs expression is highly fitness negative at supra-optimal temperatures. In contrast, deletion of Tes resulted in the loss of all GDGTs, cyclization of archaeol, and loss of viability upon transition to the stationary phase in this model archaea. These results demonstrate the critical roles of highly specialized, dynamic, isoprenoid-based lipid membranes for archaeal survival at high temperatures.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900188","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}
引用次数: 0
GRASP negatively regulates the secretion of the virulence factor gp63 in Leishmania. GRASP 负向调节利什曼原虫毒力因子 gp63 的分泌。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-04-01 DOI: 10.1111/mmi.15255
Kamal Kumar, Rituparna Basak, Aakansha Rai, Amitabha Mukhopadhyay
{"title":"GRASP negatively regulates the secretion of the virulence factor gp63 in Leishmania.","authors":"Kamal Kumar, Rituparna Basak, Aakansha Rai, Amitabha Mukhopadhyay","doi":"10.1111/mmi.15255","DOIUrl":"10.1111/mmi.15255","url":null,"abstract":"<p><p>Metalloprotease-gp63 is a virulence factor secreted by Leishmania. However, secretory pathway in Leishmania is not well defined. Here, we cloned and expressed the GRASP homolog from Leishmania. We found that Leishmania expresses one GRASP homolog of 58 kDa protein (LdGRASP) which localizes in LdRab1- and LPG2-positive Golgi compartment in Leishmania. LdGRASP was found to bind with COPII complex, LdARF1, LdRab1 and LdRab11 indicating its role in ER and Golgi transport in Leishmania. To determine the function of LdGRASP, we generated LdGRASP knockout parasites using CRISPR-Cas9. We found fragmentation of Golgi in Ld:GRASPKO parasites. Our results showed enhanced transport of non-GPI-anchored gp63 to the cell surface leading to higher secretion of this form of gp63 in Ld:GRASPKO parasites in comparison to Ld:WT cells. In contrast, we found that transport of GPI-anchored gp63 to the cell surface is blocked in Ld:GRASPKO parasites and thereby inhibits its secretion. The overexpression of dominant-negative mutant of LdRab1 or LdSar1 in Ld:GRASPKO parasites significantly blocked the secretion of non-GPI-anchored gp63. Interestingly, we found that survival of transgenic parasites overexpressing Ld:GRASP-GFP is significantly compromised in macrophages in comparison to Ld:WT and Ld:GRASPKO parasites. These results demonstrated that LdGRASP differentially regulates Ldgp63 secretory pathway in Leishmania.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336278","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}
引用次数: 0
Genomic and metabolomic diversity within a familial population of Aspergillus flavus. 黄曲霉家族种群的基因组和代谢组多样性。
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-02-23 DOI: 10.1111/mmi.15244
Geromy G Moore, Brian M Mack, Karen L Wendt, Lina Castano-Duque, Victoria M Anderson, Robert H Cichewicz
{"title":"Genomic and metabolomic diversity within a familial population of Aspergillus flavus.","authors":"Geromy G Moore, Brian M Mack, Karen L Wendt, Lina Castano-Duque, Victoria M Anderson, Robert H Cichewicz","doi":"10.1111/mmi.15244","DOIUrl":"10.1111/mmi.15244","url":null,"abstract":"<p><p>Aspergillus flavus is an agriculturally significant micro-fungus having potential to contaminate food and feed crops with toxic secondary metabolites such as aflatoxin (AF) and cyclopiazonic acid (CPA). Research has shown A. flavus strains can overcome heterokaryon incompatibility and undergo meiotic recombination as teleomorphs. Although evidence of recombination in the AF gene cluster has been reported, the impacts of recombination on genotype and metabolomic phenotype in a single generation are lacking. In previous studies, we paired an aflatoxigenic MAT1-1 A. flavus strain with a non-aflatoxigenic MAT1-2 A. flavus strain that had been tagged with green fluorescent protein and then 10 F1 progenies (a mix of fluorescent and non-fluorescent) were randomly selected from single-ascospore colonies and broadly examined for evidence of recombination. In this study, we determined four of those 10 F1 progenies were recombinants because they were not vegetatively compatible with either parent or their siblings, and they exhibited other distinctive traits that could only result from meiotic recombination. The other six progenies examined shared genomic identity with the non-aflatoxigenic, fluorescent, and MAT1-2 parent, but were metabolically distinct. This study highlights phenotypic and genomic changes that may occur in a single generation from the outcrossing of sexually compatible strains of A. flavus.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940315","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}
引用次数: 0
An essential protease, FtsH, influences daptomycin resistance acquisition in Enterococcus faecalis. 一种重要的蛋白酶 FtsH 影响粪肠球菌对达托霉素的耐药性获得。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-03-25 DOI: 10.1111/mmi.15253
Zeus Jaren Nair, Iris Hanxing Gao, Aslam Firras, Kelvin Kian Long Chong, Eric D Hill, Pei Yi Choo, Cristina Colomer-Winter, Qingyan Chen, Caroline Manzano, Kevin Pethe, Kimberly A Kline
{"title":"An essential protease, FtsH, influences daptomycin resistance acquisition in Enterococcus faecalis.","authors":"Zeus Jaren Nair, Iris Hanxing Gao, Aslam Firras, Kelvin Kian Long Chong, Eric D Hill, Pei Yi Choo, Cristina Colomer-Winter, Qingyan Chen, Caroline Manzano, Kevin Pethe, Kimberly A Kline","doi":"10.1111/mmi.15253","DOIUrl":"10.1111/mmi.15253","url":null,"abstract":"<p><p>Daptomycin is a last-line antibiotic commonly used to treat vancomycin-resistant Enterococci, but resistance evolves rapidly and further restricts already limited treatment options. While genetic determinants associated with clinical daptomycin resistance (DAP<sup>R</sup>) have been described, information on factors affecting the speed of DAP<sup>R</sup> acquisition is limited. The multiple peptide resistance factor (MprF), a phosphatidylglycerol-modifying enzyme involved in cationic antimicrobial resistance, is linked to DAP<sup>R</sup> in pathogens such as methicillin-resistant Staphylococcus aureus. Since Enterococcus faecalis encodes two paralogs of mprF and clinical DAP<sup>R</sup> mutations do not map to mprF, we hypothesized that functional redundancy between the paralogs prevents mprF-mediated resistance and masks other evolutionary pathways to DAP<sup>R</sup>. Here, we performed in vitro evolution to DAP<sup>R</sup> in mprF mutant background. We discovered that the absence of mprF results in slowed DAP<sup>R</sup> evolution and is associated with inactivating mutations in ftsH, resulting in the depletion of the chaperone repressor HrcA. We also report that ftsH is essential in the parental, but not in the ΔmprF, strain where FtsH depletion results in growth impairment in the parental strain, a phenotype associated with reduced extracellular acidification and reduced ability for metabolic reduction. This presents FtsH and HrcA as enticing targets for developing anti-resistance strategies.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288521","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}
引用次数: 0
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