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Study of excess manganese stress response highlights the central role of manganese exporter Mnx for holding manganese homeostasis in the cyanobacterium Synechocystis sp. PCC 6803. 对过量锰应激反应的研究凸显了锰输出器 Mnx 在蓝藻 Synechocystis sp. PCC 6803 中维持锰平衡的核心作用。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-11-01 DOI: 10.1099/mic.0.001515
Mara Reis, Sanja Zenker, Prisca Viehöver, Karsten Niehaus, Andrea Bräutigam, Marion Eisenhut
{"title":"Study of excess manganese stress response highlights the central role of manganese exporter Mnx for holding manganese homeostasis in the cyanobacterium <i>Synechocystis</i> sp. PCC 6803.","authors":"Mara Reis, Sanja Zenker, Prisca Viehöver, Karsten Niehaus, Andrea Bräutigam, Marion Eisenhut","doi":"10.1099/mic.0.001515","DOIUrl":"https://doi.org/10.1099/mic.0.001515","url":null,"abstract":"<p><p>Cellular levels of the essential micronutrient manganese (Mn) need to be carefully balanced within narrow borders. In cyanobacteria, a sufficient Mn supply is critical for ensuring the function of the oxygen-evolving complex as the central part of the photosynthetic machinery. However, Mn accumulation is fatal for the cells. The reason for the observed cytotoxicity is unclear. To understand the causality behind Mn toxicity in cyanobacteria, we investigated the impact of excess Mn on physiology and global gene expression in the model organism <i>Synechocystis</i> sp. PCC 6803. We compared the response of the WT and the knock-out mutant in the <i>Mn</i> e<i>x</i>porter (Mnx), ∆<i>mnx</i>, which is disabled in the export of surplus Mn and thus functions as a model for toxic Mn overaccumulation. While growth and pigment accumulation in ∆<i>mnx</i> were severely impaired 24 h after the addition of tenfold Mn, the WT was not affected and thus mounted an adequate transcriptional response. RNA-seq data analysis revealed that the Mn stress transcriptomes partly resembled an iron limitation transcriptome. However, the expression of iron limitation signature genes <i>isiABDC</i> was not affected by the Mn treatment, indicating that Mn excess is not accompanied by iron limitation in <i>Synechocystis</i>. We suggest that the ferric uptake regulator, Fur, gets partially mismetallated under Mn excess conditions and thus interferes with an iron-dependent transcriptional response. To encounter mismetallation and other Mn-dependent problems on a protein level, the cells invest in transcripts of ribosomes, proteases and chaperones. In the case of the ∆<i>mnx</i> mutant, the consequences of the disability to export excess Mn from the cytosol manifest in additionally impaired energy metabolism and oxidative stress transcriptomes with a fatal outcome. This study emphasizes the central importance of Mn homeostasis and the transporter Mnx's role in restoring and holding it.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Quantifying the fractal complexity of nutrient transport channels in Escherichia coli biofilms under varying cell shape and growth environment. 量化不同细胞形状和生长环境下大肠埃希菌生物膜中营养物质运输通道的分形复杂性。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-11-01 DOI: 10.1099/mic.0.001511
Beatrice Bottura, Liam Rooney, Morgan Feeney, Paul A Hoskisson, Gail McConnell
{"title":"Quantifying the fractal complexity of nutrient transport channels in <i>Escherichia coli</i> biofilms under varying cell shape and growth environment.","authors":"Beatrice Bottura, Liam Rooney, Morgan Feeney, Paul A Hoskisson, Gail McConnell","doi":"10.1099/mic.0.001511","DOIUrl":"https://doi.org/10.1099/mic.0.001511","url":null,"abstract":"<p><p>Recent mesoscopic characterization of nutrient-transporting channels in <i>Escherichia coli</i> has allowed the identification and measurement of individual channels in whole mature colony biofilms. However, their complexity under different physiological and environmental conditions remains unknown. Analysis of confocal micrographs of colony biofilms formed by cell shape mutants of <i>E. coli</i> shows that channels have high fractal complexity, regardless of cell phenotype or growth medium. In particular, colony biofilms formed by the mutant strain Δ<i>ompR</i>, which has a wide-cell phenotype, have a higher fractal dimension when grown on rich medium than when grown on minimal medium, with channel complexity affected by glucose and agar concentrations in the medium. Osmotic stress leads to a dramatic reduction in the Δ<i>ompR</i> cell size but has a limited effect on channel morphology. This work shows that fractal image analysis is a powerful tool to quantify the effect of phenotypic mutations and growth environment on the morphological complexity of internal <i>E. coli</i> biofilm structures. If applied to a wider range of mutant strains, this approach could help elucidate the genetic determinants of channel formation in <i>E. coli</i> colony biofilms.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Microbiome-derived metabolite effects on intestinal barrier integrity and immune cell response to infection. 微生物衍生代谢物对肠道屏障完整性和免疫细胞感染反应的影响。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001504
Lauren Adams, Xiang Li, Richard Burchmore, Richard J A Goodwin, Daniel M Wall
{"title":"Microbiome-derived metabolite effects on intestinal barrier integrity and immune cell response to infection.","authors":"Lauren Adams, Xiang Li, Richard Burchmore, Richard J A Goodwin, Daniel M Wall","doi":"10.1099/mic.0.001504","DOIUrl":"10.1099/mic.0.001504","url":null,"abstract":"<p><p>The gut microbiota exerts a significant influence on human health and disease. While compositional changes in the gut microbiota in specific diseases can easily be determined, we lack a detailed mechanistic understanding of how these changes exert effects at the cellular level. However, the putative local and systemic effects on human physiology that are attributed to the gut microbiota are clearly being mediated through molecular communication. Here, we determined the effects of gut microbiome-derived metabolites l-tryptophan, butyrate, trimethylamine (TMA), 3-methyl-4-(trimethylammonio)butanoate (3,4-TMAB), 4-(trimethylammonio)pentanoate (4-TMAP), ursodeoxycholic acid (UDCA), glycocholic acid (GCA) and benzoate on the first line of defence in the gut. Using <i>in vitro</i> models of intestinal barrier integrity and studying the interaction of macrophages with pathogenic and non-pathogenic bacteria, we could ascertain the influence of these metabolites at the cellular level at physiologically relevant concentrations. Nearly all metabolites exerted positive effects on barrier function, but butyrate prevented a reduction in transepithelial resistance in the presence of the pathogen <i>Escherichia coli</i>, despite inducing increased apoptosis and exerting increased cytotoxicity. Induction of IL-8 was unaffected by all metabolites, but GCA stimulated increased intra-macrophage growth of <i>E. coli</i> and tumour necrosis-alpha (TNF-α) release. Butyrate, 3,4-TMAB and benzoate all increased TNF-α release independent of bacterial replication. These findings reiterate the complexity of understanding microbiome effects on host physiology and underline that microbiome metabolites are crucial mediators of barrier function and the innate response to infection. Understanding these metabolites at the cellular level will allow us to move towards a better mechanistic understanding of microbiome influence over host physiology, a crucial step in advancing microbiome research.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Investigating trends in antibiotic resistance of Escherichia coli isolated from clinical urine specimens in the Orkney Islands. 调查从奥克尼群岛临床尿液标本中分离出的大肠埃希菌的抗生素耐药性趋势。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001514
Lily Corse, Allison Cartwright
{"title":"Investigating trends in antibiotic resistance of <i>Escherichia coli</i> isolated from clinical urine specimens in the Orkney Islands.","authors":"Lily Corse, Allison Cartwright","doi":"10.1099/mic.0.001514","DOIUrl":"10.1099/mic.0.001514","url":null,"abstract":"<p><p>Urinary tract infections (UTIs) are extremely common, affecting people of all ages and health statuses. Although UTIs do not usually cause severe illness, in some cases they can lead to more serious complications, especially if their initial treatment is ineffective due to antimicrobial resistance (AMR). AMR is an increasing issue, exacerbated by misdiagnosis and inappropriate prescribing of antibiotics, thus facilitating further resistance. The aim of this study was to investigate the rates of AMR in <i>Escherichia coli</i> isolated from clinical urine specimens tested at the Balfour Hospital, Orkney, and determine trends related to patient risk factors. Antibiotic susceptibilities were tested for 100 isolates of uropathogenic <i>E. coli</i> using the VITEK 2 Compact (bioMérieux), and data were analysed using percentage resistance rates. Resistance rates were compared by patient sex, age and source (hospital versus community). The findings showed higher AMR in males compared with females, particularly for trimethoprim (TMP), with 52% in males and only 12% in females. AMR tended to be higher in <i>E. coli</i> isolated from hospital inpatients than from community specimens, except for amoxicillin (AMX) and co-amoxiclav. Finally, the study found that AMR of <i>E. coli</i> isolates was greater in patients aged over 50 than 18-50 years old, particularly for AMX and TMP. The highest resistance rates across all patient demographics were for AMX, implying that the use of this antibiotic for the treatment of <i>E. coli</i> UTIs is not appropriate.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Outer membrane barrier impairment by envC deletion reduces gut colonization of Crohn's disease pathobiont Escherichia coli. envC缺失导致外膜屏障受损,从而减少了克罗恩病致病大肠杆菌的肠道定植。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001509
Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim
{"title":"Outer membrane barrier impairment by <i>envC</i> deletion reduces gut colonization of Crohn's disease pathobiont <i>Escherichia coli</i>.","authors":"Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim","doi":"10.1099/mic.0.001509","DOIUrl":"10.1099/mic.0.001509","url":null,"abstract":"<p><p>Adherent-invasive <i>Escherichia coli</i> (AIEC) has been implicated in the aetiology of Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract. The presence of <i>Enterobacteriaceae</i>, including AIEC, is heightened in the intestines of CD patients. Therefore, inhibiting AIEC colonization in the gastrointestinal tract could be a promising therapeutic intervention for CD. This study aims to assess the potential of EnvC as a novel therapeutic target, examining how disrupting EnvC activity through the deletion of the <i>envC</i> gene decreases AIEC gut colonization levels. EnvC serves as a catalyst for peptidoglycan (also called murein) amidases, facilitating bacterial cell division. An AIEC mutant lacking the <i>envC</i> gene exhibited impaired cell division. Furthermore, <i>envC</i> deletion led to a diminished outer membrane barrier, as seen in our finding that the <i>envC</i> mutant became susceptible to vancomycin. Finally, we found that the <i>envC</i> mutant is impaired in competitive gut colonization in a dysbiotic mouse model. The colonization defects might be attributable to reduced resistance to colonic bile acids, as evidenced by our finding that increased colonic levels of bile acids inhibited the colonization of the gastrointestinal tract by AIEC strains. The present findings suggest that targeting bacterial cell division through the inhibition of EnvC activity could represent a promising intervention for CD.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 current riboswitch landscape in Clostridioides difficile. 艰难梭菌目前的核糖开关状况。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001508
Adriana Badilla Lobo, Olga Soutourina, Johann Peltier
{"title":"The current riboswitch landscape in <i>Clostridioides difficile</i>.","authors":"Adriana Badilla Lobo, Olga Soutourina, Johann Peltier","doi":"10.1099/mic.0.001508","DOIUrl":"https://doi.org/10.1099/mic.0.001508","url":null,"abstract":"<p><p>Riboswitches are 5' RNA regulatory elements that are capable of binding to various ligands, such as small metabolites, ions and tRNAs, leading to conformational changes and affecting gene transcription or translation. They are widespread in bacteria and frequently control genes that are essential for the survival or virulence of major pathogens. As a result, they represent promising targets for the development of new antimicrobial treatments. <i>Clostridioides difficile</i>, a leading cause of antibiotic-associated nosocomial diarrhoea in adults, possesses numerous riboswitches in its genome. Accumulating knowledge of riboswitch-based regulatory mechanisms provides insights into the potential therapeutic targets for treating <i>C. difficile</i> infections. This review offers an in-depth examination of the current state of knowledge regarding riboswitch-mediated regulation in <i>C. difficile</i>, highlighting their importance in bacterial adaptability and pathogenicity. Particular attention is given to the ligand specificity and function of known riboswitches in this bacterium. The review also discusses the recent progress that has been made in the development of riboswitch-targeting compounds as potential treatments for <i>C. difficile</i> infections. Future research directions are proposed, emphasizing the need for detailed structural and functional analyses of riboswitches to fully harness their regulatory capabilities for developing new antimicrobial strategies.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Biotin concentration affects anaplerotic reactions functioning in glutamic acid production in Corynebacterium glutamicum. 生物素浓度会影响谷氨酸棒状杆菌产生谷氨酸的无机反应。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001507
Takako Ochiai, Masaaki Wachi, Takashi Hirasawa
{"title":"Biotin concentration affects anaplerotic reactions functioning in glutamic acid production in <i>Corynebacterium glutamicum</i>.","authors":"Takako Ochiai, Masaaki Wachi, Takashi Hirasawa","doi":"10.1099/mic.0.001507","DOIUrl":"10.1099/mic.0.001507","url":null,"abstract":"<p><p>The study investigates the effect of biotin concentration on the role of anaplerotic reactions catalysed by pyruvate carboxylase (PC) and phosphoenolpyruvate carboxylase (PEPC) in glutamic acid production by <i>Corynebacterium glutamicum. C. glutamicum</i> requires biotin for its growth, and its glutamic acid production can be induced by the addition of Tween 40 or penicillin or by biotin limitation. The biotin enzyme PC and the non-biotin enzyme PEPC catalyse two anaplerotic reactions to supply oxaloacetic acid to the TCA cycle in <i>C. glutamicum</i>. Therefore, they are crucial for glutamic acid production in this bacterium. In this study, we investigated the contribution of each anaplerotic reaction to Tween 40- and penicillin-induced glutamic acid production using disruptants of PEPC and PC. In the presence of 20 µg l<sup>-1</sup> biotin, which is sufficient for growth, the PEPC-catalysed anaplerotic reaction mainly contributed to Tween 40- and penicillin-induced glutamic acid production. However, when increasing biotin concentration 10-fold (i.e. 200 µg l<sup>-1</sup>), both PC- and PEPC-catalysed reactions could function in glutamic acid production. Western blotting revealed that the amount of biotin-bound PC was reduced by the addition of Tween 40 and penicillin in the presence of 20 µg l<sup>-1</sup>. However, these induction treatments did not change the amount of biotin-bound PC in the presence of 200 µg l<sup>-1</sup> biotin. These results indicate that both anaplerotic reactions are functional during glutamic acid production in <i>C. glutamicum</i> and that biotin concentration mainly affects which anaplerotic reactions function during glutamic acid production.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Selective colonization of microplastics, wood and glass by antimicrobial-resistant and pathogenic bacteria. 抗菌细菌和致病细菌在微塑料、木材和玻璃上的选择性定殖。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001506
Emily M Stevenson, Owen Rushby-Jones, Angus Buckling, Matthew Cole, Penelope K Lindeque, Aimee K Murray
{"title":"Selective colonization of microplastics, wood and glass by antimicrobial-resistant and pathogenic bacteria.","authors":"Emily M Stevenson, Owen Rushby-Jones, Angus Buckling, Matthew Cole, Penelope K Lindeque, Aimee K Murray","doi":"10.1099/mic.0.001506","DOIUrl":"https://doi.org/10.1099/mic.0.001506","url":null,"abstract":"<p><p>The Plastisphere is a novel niche whereby microbial communities attach to plastic debris, including microplastics. These communities can be distinct from those found in the surrounding environment or those attached to natural substrates and may serve as a reservoir of both pathogenic and antimicrobial-resistant (AMR) bacteria. Owing to the frequent omission of appropriate comparator particles (e.g. natural substrates) in previous studies, there is a lack of empirical evidence supporting the unique risks posed by microplastics in terms of enrichment and spread of AMR pathogens. This study investigated selective colonization by a sewage community on environmentally sampled microplastics with three different polymers, sources and morphologies, alongside natural substrate (wood), inert substrate (glass) and free-living/planktonic community controls. Culture and molecular methods (quantitative polymerase chain reaction (qPCR)) were used to ascertain phenotypic and genotypic AMR prevalence, respectively, and multiplex colony PCR was used to identify extra-intestinal pathogenic <i>Escherichia coli</i> (ExPECs). From this, polystyrene and wood particles were found to significantly enrich AMR bacteria, whereas sewage-sourced bio-beads significantly enriched ExPECs. Polystyrene and wood were the least smooth particles, and so the importance of particle roughness on AMR prevalence was then directly investigated by comparing the colonization of virgin vs artificially weathered polyethylene particles. Surface weathering did not have a significant effect on the AMR prevalence of colonized particles. Our results suggest that the colonization of plastic and non-plastic particles by AMR and pathogenic bacteria may be enhanced by substrate-specific traits.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Understanding the clinical and environmental drivers of antifungal resistance in the One Health context. 了解 "一体健康 "背景下抗真菌耐药性的临床和环境驱动因素。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001512
Catrin C Williams, Jack B Gregory, Jane Usher
{"title":"Understanding the clinical and environmental drivers of antifungal resistance in the One Health context.","authors":"Catrin C Williams, Jack B Gregory, Jane Usher","doi":"10.1099/mic.0.001512","DOIUrl":"10.1099/mic.0.001512","url":null,"abstract":"<p><p>Antifungal drugs have had a tremendous impact on human health and the yields of crops. However, in recent years, due to usage both in a health setting and in agriculture, there has been a rapid emergence of antifungal drug resistance that has outpaced novel compound discovery. It is now globally recognized that new strategies to tackle fungal infection are urgently needed, with such approaches requiring the cooperation of both sectors and the development of robust antifungal stewardship rationales. In this review, we examine the current antifungal regimes in clinical and agricultural settings, focusing on two pathogens of importance, <i>Candida auris</i> and <i>Aspergillus fumigatus,</i> examining their drivers of antifungal resistance, the impact of dual-use azoles and the impact agricultural practices have on driving the emergence of resistance. Finally, we postulate that a One Health approach could offer a viable alternative to prolonging the efficacy of current antifungal agents.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Cryo-electron microscopy structure of the di-domain core of Mycobacterium tuberculosis polyketide synthase 13, essential for mycobacterial mycolic acid synthesis. 结核分枝杆菌多酮合成酶 13 的二域核心的冷冻电子显微镜结构,该酶对分枝杆菌霉菌酸的合成至关重要。
IF 2.6 4区 生物学
Microbiology-Sgm Pub Date : 2024-10-01 DOI: 10.1099/mic.0.001505
Hannah E Johnston, Sarah M Batt, Alistair K Brown, Christos G Savva, Gurdyal S Besra, Klaus Fütterer
{"title":"Cryo-electron microscopy structure of the di-domain core of <i>Mycobacterium tuberculosis</i> polyketide synthase 13, essential for mycobacterial mycolic acid synthesis.","authors":"Hannah E Johnston, Sarah M Batt, Alistair K Brown, Christos G Savva, Gurdyal S Besra, Klaus Fütterer","doi":"10.1099/mic.0.001505","DOIUrl":"https://doi.org/10.1099/mic.0.001505","url":null,"abstract":"<p><p>Mycobacteria are known for their complex cell wall, which comprises layers of peptidoglycan, polysaccharides and unusual fatty acids known as mycolic acids that form their unique outer membrane. Polyketide synthase 13 (Pks13) of <i>Mycobacterium tuberculosis</i>, the bacterial organism causing tuberculosis, catalyses the last step of mycolic acid synthesis prior to export to and assembly in the cell wall. Due to its essentiality, Pks13 is a target for several novel anti-tubercular inhibitors, but its 3D structure and catalytic reaction mechanism remain to be fully elucidated. Here, we report the molecular structure of the catalytic core domains of <i>M. tuberculosis</i> Pks13 (Mt-Pks13), determined by transmission cryo-electron microscopy (cryoEM) to a resolution of 3.4 Å. We observed a homodimeric assembly comprising the ketoacyl synthase (KS) domain at the centre, mediating dimerization, and the acyltransferase (AT) domains protruding in opposite directions from the central KS domain dimer. In addition to the KS-AT di-domains, the cryoEM map includes features not covered by the di-domain structural model that we predicted to contain a dimeric domain similar to dehydratases, yet likely lacking catalytic function. Analytical ultracentrifugation data indicate a pH-dependent equilibrium between monomeric and dimeric assembly states, while comparison with the previously determined structures of <i>M. smegmatis</i> Pks13 indicates architectural flexibility. Combining the experimentally determined structure with modelling in AlphaFold2 suggests a structural scaffold with a relatively stable dimeric core, which combines with considerable conformational flexibility to facilitate the successive steps of the Claisen-type condensation reaction catalysed by Pks13.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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