Wenzhong Zhu , Yuan Hu , Yongping Shi , Haijun Bao , Xukai Cheng , Mi Jiang , Zuojie Peng , Jia Song , Feifei Fang , Chenxing Jian , Wenzheng Yuan , Jinghuang Chen , Xiaogang Shu
{"title":"Sleep deprivation accelerates Parkinson's disease via modulating gut microbiota associated microglial activation and oxidative stress","authors":"Wenzhong Zhu , Yuan Hu , Yongping Shi , Haijun Bao , Xukai Cheng , Mi Jiang , Zuojie Peng , Jia Song , Feifei Fang , Chenxing Jian , Wenzheng Yuan , Jinghuang Chen , Xiaogang Shu","doi":"10.1016/j.micres.2025.128077","DOIUrl":"10.1016/j.micres.2025.128077","url":null,"abstract":"<div><div>The interplay between Parkinson’s disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress. To test this hypothesis, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), then subjected the mice to SD. A battery of behavioral tests, including rotarod, pole, adhesive removal, and open field tests, were used to assess motor function. Our study showed that SD exacerbated motor deficits, loss of tyrosine hydroxylase (TH), microglial activation and oxidative stress damage in PD model mice. Fecal microbiota transplantation experiments revealed that SD mediated PD progression, microglial activation and oxidative stress via the gut microbiota. 16S rRNA sequencing analysis indicated that SD increased the abundances of bacteria such as Bacteroidaceae, while decreasing the abundances of bacteria including <em>Lactobacillus</em>. Non-targeted metabolomic analysis of gut microbiota-derived metabolites revealed that SD significantly increased the production of adenosine (ADO), a purine metabolite. Probiotic supplementation reversed the effects of SD on motor deficits, dopaminergic neuron loss, microglial activation and oxidative stress damage in PD mice; it also decreased SD-induced ADO production. Administration of Adenosine A2A receptor (A2AR) inhibitors, Istradefylline (Ist), attenuated the roles of SD and ADO in promoting microglial activation, oxidative stress and PD progression. Taken together, our findings indicate that SD accelerates PD progression via regulating microbiota associated microglial activation and oxidative stress, suggesting that efforts to improve sleep quality can be used to prevent and treat PD.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128077"},"PeriodicalIF":6.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanan Qu , Xuechen Yang , Minghao Zhang , Junda Chen , Yushu Sui , Xiaochong Zhang , Yizhu Zeng , Muping Huang , Yifan Gao , Raúl Ochoa-Hueso , Baoku Shi , Daiqi Zhao , Tianxue Yang , Wei Sun
{"title":"Bacterial and fungal diversity and species interactions inversely affect ecosystem functions under drought in a semi-arid grassland","authors":"Yanan Qu , Xuechen Yang , Minghao Zhang , Junda Chen , Yushu Sui , Xiaochong Zhang , Yizhu Zeng , Muping Huang , Yifan Gao , Raúl Ochoa-Hueso , Baoku Shi , Daiqi Zhao , Tianxue Yang , Wei Sun","doi":"10.1016/j.micres.2025.128075","DOIUrl":"10.1016/j.micres.2025.128075","url":null,"abstract":"<div><div>Extreme climatic events, such as drought, can significantly alter belowground microbial diversity and species interactions, leading to unknown consequences for ecosystem functioning. Here, we simulated a drought gradient by removing 30 %, 50 %, and 70 % of precipitation in a semi-arid grassland over five years. We assessed the effects of drought on bacterial and fungal diversity, as well as on their species interactions. We also evaluated the impact of drought on ecosystem individual functions (e.g., plant biomass and microbial activity), and on multifunctionality (EMF). Finally, we linked the drought-induced changes in microbial communities with the variations in EMF. Drought significantly increased fungal diversity and intensified species interactions, but it decreased bacterial diversity and species interactions. Both plant and microbial biomass significantly decreased with increasing drought severity, while microbial activity showed the opposite trend. Only the −50 % rainfall treatment notably reduced EMF. Bacterial diversity and species interactions positively correlated with most ecosystem functions. However, fungal parameters were negatively associated with these functions. Structural equation modeling indicated that bacterial diversity had a strong direct positive effect on EMF (standardized path coefficient: 0.52), and that bacterial diversity was indirectly suppressed by drought through decreasing soil water content and bacterial phospholipid fatty acids (PLFAs). In contrast, fungal species interactions had a significant direct negative effect on EMF with the highest standardized path coefficient (−0.6) and were directly enhanced by fungal diversity. Drought had indirect positive effects on fungal diversity by decreasing soil water content and stimulating fungal PLFAs. Our results highlight the importance of considering soil microbial species interactions when evaluating the ecological impacts of drought. Furthermore, the divergent regulatory pathways of bacterial and fungal communities to EMF suggest that improving ecosystem functionality may be achieved by enhancing bacterial diversity while mitigating fungal species interactions through reducing fungal diversity.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128075"},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silindile Maphosa , Mégan Steyn , Pedro H. Lebre , Jarishma K. Gokul , Peter Convey , Eugene Marais , Gillian Maggs-Kölling , Don A. Cowan
{"title":"Rhizosphere bacterial communities of Namib Desert plant species: Evidence of specialised plant-microbe associations","authors":"Silindile Maphosa , Mégan Steyn , Pedro H. Lebre , Jarishma K. Gokul , Peter Convey , Eugene Marais , Gillian Maggs-Kölling , Don A. Cowan","doi":"10.1016/j.micres.2025.128076","DOIUrl":"10.1016/j.micres.2025.128076","url":null,"abstract":"<div><div>Rhizosphere microbial communities are intimately associated with plant root surfaces. The rhizosphere microbiome is recruited from the surrounding soil and is known to impact positively on the plant host via enhanced resistance to pathogens, increased nutrient availability, growth stimulation and increased resistance to desiccation. Desert ecosystems harbour a diversity of perennial and annual plant species, generally exhibiting considerable physiological adaptation to the low-water environment. In this study, we explored the rhizosphere bacterial microbiomes associated with selected desert plant species. The rhizosphere bacterial communities of 11 plant species from the central Namib Desert were assessed using 16S rRNA gene-dependent phylogenetic analyses. The rhizosphere microbial community of each host plant species was compared with control soils collected from their immediate vicinity, and with those of all other host plants. Rhizosphere and control soil bacterial communities differed significantly and were influenced by both location and plant species. Rhizosphere-associated genera included 67 known plant growth-promoting taxa, including <em>Rhizobium</em>, <em>Bacillus</em>, <em>Microvirga</em>, <em>Kocuria</em> and <em>Paenibacillus</em>. Other than <em>Kocuria</em>, these genera constituted the ‘core’ rhizosphere bacterial microbiome, defined as being present in > 90 % of the rhizosphere communities. Nine of the 11 desert plant species harboured varying numbers and proportions of species-specific microbial taxa. Predictive analyses of functional pathways linked to rhizosphere microbial taxa showed that these were significantly enriched in the biosynthesis or degradation of a variety of substances such as sugars, secondary metabolites, phenolic compounds and antimicrobials. Overall, our data suggest that plant species in the Namib Desert recruit unique taxa to their rhizosphere bacterial microbiomes that may contribute to their resilience in this extreme environment.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128076"},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinqing Ou , Siyuan Zhang , Mingyang Zhang , Jingyuan Zhang , Jiahong Xu , Nan Zhang , Yantao Jia
{"title":"Responding to exogenous quorum-sensing signals promotes defense against phages by repressing OmpV expression in Pseudomonas syringae pv. actinidiae","authors":"Jinqing Ou , Siyuan Zhang , Mingyang Zhang , Jingyuan Zhang , Jiahong Xu , Nan Zhang , Yantao Jia","doi":"10.1016/j.micres.2025.128074","DOIUrl":"10.1016/j.micres.2025.128074","url":null,"abstract":"<div><div>Bacteriophages as viral predators can restrict host strains and shape the bacterial community. Conversely, bacteria also adopt diverse strategies for phage defense. <em>Pseudomonas syringae</em> pv. <em>actinidiae</em> (<em>Psa</em>) is the causal agent of bacterial canker on kiwifruit. Though <em>Psa</em> lacks quorum sensing signaling molecule synthase LuxI, two (PsaR1 and PsaR3) of three LuxR homologous were confirmed to bind with exogenous N-acyl homoserine lactone (AHL), OXO-C8-HSL. The adsorption and infection efficiency of phage KBC54 to <em>Psa</em> significantly reduced by adding OXO-C8-HSL or heterologous expression of <em>traI</em> of <em>Agrobacterium tumefaciens</em> in <em>Psa</em>. By generating <em>PsaR1</em> and <em>PsaR3</em> mutants, as well as PsaR-AHL MST assays, we specified that the two PsaRs can recruit AHL to enhance bacterial resistance against phage. Absence of <em>PsaR1</em> and <em>PsaR3</em> resulted in up-regulation of the outer membrane protein OmpV, and knockout of <em>ompV</em> led to impaired phage adsorption efficiency. Given that OmpV specifically interacted with the phage tail fiber protein Tp3 in pull-down assay, we deduced that OmpV serves as a cell surface receptor recognized by phage. This study highlights the remarkable ability of <em>Psa</em> recruiting QS signals to inhibit phage infection. This may be a common strategy for non-AHL producing bacteria that evolved to take control of phage infection and promote host fitness by orchestrating QS signals in living niches.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128074"},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qianwei Qu , Mengmeng Zhao , Haixin Peng , Zhenxin Zhu , Long Chen , Haojie Wu , Xiaona Liu , Yue Dong , Kang An , Yadan Zheng , Zhiyun Zhang , Yanyan Liu , Haoran Wang , Na Dong , Chunliu Dong , Yanhua Li
{"title":"Glabridin restore the sensitivity of colistin against mcr-1-positive Escherichia coli by polypharmacology mechanism","authors":"Qianwei Qu , Mengmeng Zhao , Haixin Peng , Zhenxin Zhu , Long Chen , Haojie Wu , Xiaona Liu , Yue Dong , Kang An , Yadan Zheng , Zhiyun Zhang , Yanyan Liu , Haoran Wang , Na Dong , Chunliu Dong , Yanhua Li","doi":"10.1016/j.micres.2025.128070","DOIUrl":"10.1016/j.micres.2025.128070","url":null,"abstract":"<div><div>The clinical effectiveness of colistin against multidrug-resistant Gram-negative pathogen infections has been threatened by the emergence of the plasmid-mediated colistin-resistant gene <em>mcr-1</em>. This development underscores the urgent need for innovative therapeutic strategies that target resistance mechanisms. In this study, we demonstrated that glabridin can restore the sensitivity of colistin to <em>mcr</em>-<em>1</em>-positive <em>Escherichia coli</em> (<em>E. coli</em>) and exhibits a reduced propensity for resistance development. Our investigation into the underlying mechanisms revealed that glabridin may re-sensitize <em>E. coli</em> to colistin by targeting MCR-1 to inhibit its activity, regulating the expression of <em>mcr</em>-<em>1</em>, and restoring the Zeta potential at the cell membrane surface. Furthermore, the combination of glabridin and colistin increased bacterial membrane permeability, decreased membrane fluidity, disrupted transmembrane proton motive force (PMF), reduced the ratios of NAD<sup>+</sup>/NADH and FAD/FADH<sub>2</sub>, facilitated the tricarboxylic acid (TCA) cycle, and led to the accumulation of reactive oxygen species (ROS) in <em>E. coli</em> cells, ultimately resulting in bacterial death. In animal models, glabridin significantly enhanced the efficacy of colistin in treating <em>E. coli</em> infections. Our findings suggest that glabridin is a promising polypharmacological antibiotic adjuvant for addressing infections associated with colistin-resistant <em>E. coli</em>.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128070"},"PeriodicalIF":6.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Sun , Dandan Wang , Xiaolin Liu , Yanan Zhou , Shuaibing Wang , Xin Guan , Weiwei Huang , Chao Wang , Biao Gong , Zhihong Xie
{"title":"The GlnE protein of Azorhizobium caulinodans ORS571 plays a crucial role in the nodulation process of the legume host Sesbania rostrata","authors":"Li Sun , Dandan Wang , Xiaolin Liu , Yanan Zhou , Shuaibing Wang , Xin Guan , Weiwei Huang , Chao Wang , Biao Gong , Zhihong Xie","doi":"10.1016/j.micres.2025.128072","DOIUrl":"10.1016/j.micres.2025.128072","url":null,"abstract":"<div><div>The GlnE enzyme, functioning as an adenylyltransferase/adenylyl-removing enzyme, plays a crucial role in reversible adenylylation of glutamine synthetase (GS), which in turn regulates bacterial nitrogen assimilation. Genomic analysis of <em>Azorhizobium caulinodans</em> ORS571 revealed an open reading frame encoding a GlnE protein, whose function in the free-living and symbiotic states remains to be elucidated. A <em>glnE</em> deletion mutant retained high GS activity even under nitrogen-rich conditions. However, a reduction in growth was observed for the mutant strain at lower NH<sub>4</sub><sup>+</sup> concentrations than for the wild-type strain. Furthermore, the Δ<em>glnE</em> mutant strain showed reduced motility on ammonium-containing media. Inactivation of GlnE led to an increase in root adhesion, biofilm formation, and nodulation on <em>Sesbania rostrata</em>. Nevertheless, the nodules induced by the <em>glnE</em> mutant strain were ineffective. In addition, <em>A. caulinodans</em> GlnE played a significant role in enhancing resistance against environmental stresses, such as heat, heavy metals, and cumene hydroperoxide. This study demonstrates that GlnE plays multiple regulatory roles in <em>A. caulinodans</em> beyond nitrogen metabolism and is essential for establishing symbiotic relationships with host plants.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128072"},"PeriodicalIF":6.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaili Jiang , Pan Luo , Xinxin Wang , Ping Song , Jingjing Chen , Ling Lu
{"title":"Clarification of the biosynthetic gene cluster involved in the antifungal prodrug echinocandin B and its robust production in engineered Aspergillus pachycristatus","authors":"Kaili Jiang , Pan Luo , Xinxin Wang , Ping Song , Jingjing Chen , Ling Lu","doi":"10.1016/j.micres.2025.128069","DOIUrl":"10.1016/j.micres.2025.128069","url":null,"abstract":"<div><div>Echinocandin antifungals exhibit high efficacy against drug-resistant strains due to their unique mechanism of action. The production of their semi-synthetic precursors relies solely on microbial metabolism, leading to elevated production costs. Anidulafungin, an excellent echinocandin drug, is derived from echinocandin B (ECB), which is industrially produced by <em>Aspergillus pachycristatus</em>. However, the genes involved in the actual ECB biosynthesis remain unclear, which hinders yield improvements through engineered strains. This study systematically investigated the putative ECB biosynthetic gene cluster using genomic and transcriptomic profiling combined with gene editing. Among the 18 putative genes previously reported, only a 13-gene cluster (<em>ecdA</em>, <em>ecdG</em>-<em>J</em>, <em>htyA</em>-<em>F</em>) was found to be actively involved in ECB biosynthesis, while the remaining 5 genes (<em>ecdB</em>-<em>F</em>) were non-essential and functioned independently. Notably, we identified that <em>htyC</em> and <em>htyD</em> were involved in L-homotyrosine biosynthesis, while HtyF catalyzed the C4 hydroxylation of 3S-hydroxyl-L-homotyrosine. Most importantly, EcdJ was identified as a crucial global transcriptional activator regulating the ECB gene cluster. Deletion of <em>ecdJ</em> silenced all related genes and abolished ECB production. Accordingly, overexpressing <em>ecdJ</em> alone or combining <em>ecdA</em> and <em>htyF</em> together significantly enhanced ECB yield. Under optimized liquid fermentation conditions, ECB production in the OE<em>ecdJ</em> strain achieved 841 ± 23.11 mg/L. Solid-state fermentation further enhanced the ECB yield to 1.5 g/L, which is 7.7-fold higher than that of the wild-type strain under initial liquid fermentation conditions. This study has thoroughly elucidated the functions of key genes involved in the ECB biosynthesis and provided effective strategies for enhancing antifungal prodrug-ECB production, achieving the highest ECB production in an engineering <em>A. pachycristatus</em> strain.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128069"},"PeriodicalIF":6.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miloud Sabri , Kaoutar El Handi , Cosima Damiana Calvano , Mariachiara Bianco , Angelo De Stradis , Franco Valentini , Toufic Elbeaino
{"title":"Leuconostoc mesenteroides strain MS4-derived bacteriocins: A potent antimicrobial arsenal for controlling Xylella fastidiosa infection","authors":"Miloud Sabri , Kaoutar El Handi , Cosima Damiana Calvano , Mariachiara Bianco , Angelo De Stradis , Franco Valentini , Toufic Elbeaino","doi":"10.1016/j.micres.2025.128071","DOIUrl":"10.1016/j.micres.2025.128071","url":null,"abstract":"<div><div><em>Xylella fastidiosa</em> subsp. <em>pauca</em> (<em>Xfp</em>) currently presents a serious threat to agriculture in Europe and in the Mediterranean, following its discovery in several countries. Addressing this bacterial plant disease with traditional agricultural practices and management strategies has proven inadequate, highlighting the urgent need for effective and environmentally safe antibacterial solutions. In this study, we explored the antibacterial activity of the lactic acid bacterium <em>Leuconostoc mesenteroides</em> strain MS4-derived bacteriocins against <em>Xfp,</em> utilizing a combination of <em>in vitro</em> and <em>in planta</em> experiments. In particular, the cell-free precipitate (CFP) derived from strain MS4 culture in MRS broth, suppressed <em>Xfp</em> growth on BCYE agar plate<em>,</em> whereas protease K-treated CFP was inactive, highlighting the presence of antimicrobial compounds of proteinaceous nature. Additionally, fluorescence and transmission electron microscopy analyses showed that the CFP exhibits a bactericidal effect on <em>Xfp</em> cells, characterized by membrane disruption and subsequent cellular damage. The whole-genome sequencing and bioinformatic analysis revealed that MS4 genome consists of a circular chromosome of 1860,891 bp and a circular plasmid of 37,317 bp and most importantly to encompass six bacteriocin-encoding genes, with a peptide size ranging from 45 to 59 amino acids. MALDI-TOF/TOF MS and RPLC-ESI-MS assays performed on cell-free supernatant (CFS) confirmed the secretion of four (out of 6) bacteriocins (denoted MK-45, MR-53, MW-56, and MG-58) by MS4 in MRS broth. In spot assays, these bacteriocins displayed significant lethality against <em>Xfp</em>, with a minimum lethal concentration between 0.2 and 0.4 mg/mL. The application of CFP on <em>Xfp</em>-infected <em>Nicotiana benthamiana</em> plants, implemented both as preventive and curative approach, successfully controlled the infection, resulting in no visible symptoms 40 days post-inoculation. The finding of MS4 as a natural source of various potent bacteriocins against <em>Xfp</em>, coupled with a significant production under low-cost and uncomplicated laboratory conditions, make of MS4 a cost-effective and realistic option for sustainable management of <em>Xf</em>-related diseases.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128071"},"PeriodicalIF":6.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farhan R. Chowdhury , Laura Domínguez Mercado , Katya Kharitonov , Brandon L. Findlay
{"title":"De novo evolution of antibiotic resistance to Oct-TriA1","authors":"Farhan R. Chowdhury , Laura Domínguez Mercado , Katya Kharitonov , Brandon L. Findlay","doi":"10.1016/j.micres.2025.128056","DOIUrl":"10.1016/j.micres.2025.128056","url":null,"abstract":"<div><div>The rise of antimicrobial resistance as a global health concern has led to a strong interest in compounds able to inhibit the growth of bacteria without detectable levels of resistance evolution. A number of these compounds have been reported in recent years, including the tridecaptins, a small family of lipopeptides typified by the synthetic analogue octyl-tridecaptin A<sub>1</sub>. Hypothesizing that prior reports of negligible resistance evolution have been due in part to limitations in the laboratory evolution systems used, we have attempted to select for resistant mutants using a soft agar gradient evolution (SAGE) system developed by our lab. Following optimization of the media conditions by incorporation of the anti-synaeresis agent xanthan gum into the agar matrix, we successfully evolved high-level resistance to both octyl-tridecaptin A<sub>1</sub> as well as the challenging lipopeptide antibiotic polymyxin B. Decreased tridecaptin susceptibility was linked to mutations in outer membrane proteins <em>ompC</em>, <em>lptD</em> and <em>mlaA</em>, with the effect of these genes confirmed through a mix of allelic replacement and knockout studies. Overall, this work demonstrates the robust evolutionary potential of bacteria, even in the face of challenging antimicrobial agents.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"293 ","pages":"Article 128056"},"PeriodicalIF":6.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}