Microbiological research最新文献_第10页

Citrus fruit microbiome changes under copper-based and biological alternative treatments and its biocontrol potential 铜基和生物替代处理下柑橘果实微生物组的变化及其生物防治潜力

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-23 DOI: 10.1016/j.micres.2025.128346

M.F. Lombardo , A. Abdelfattah , V. Catara , N. Wang , G. Cirvilleri

Citrus, a globally significant fruit crop, harbours a distinctive microbial community crucial for maintaining citrus health and enhancing disease resistance. While the structure and shaping factors, including phytosanitary treatments, of citrus root and leaf microbiomes are well documented, the carposphere (fruit surface) microbiome and its response to phytosanitary inputs remain poorly understood. In the present study, we combined culture independent (amplicon sequencing) and culture dependent techniques to analyse the citrus carposphere microbiome across three citrus hosts and its response to field-applied phytosanitary treatments (biologicals and copper-antimicrobials). Despite host-specific variation in the relative abundance of dominant taxa such as Proteobacteria, Firmicutes, and Basidiomycota, all three citrus hosts shared a core microbiome, consistently present across fruit samples. Bacterial diversity and composition were negatively influenced by copper treatments, whereas biological products (chitosan, sweet orange essential oils and their mixtures) had minimal or no negative impacts. Fungal communities, including potential pathogens, appeared less sensitive to treatments. Network analysis confirmed that copper altered microbial interactions, increasing mutual exclusion relationships between bacterial taxa compared to untreated or biologically treated samples, which were dominated by positive interactions. A parallel survey of cultivable microbiota from the same samples identified potential biocontrol agents (BCAs) against Colletotrichum gloeosporioides and Alternaria alternata. Notably, cross-referencing cultivable BCAs with core Amplicon Sequence Variants (ASVs) showed that 81.7 % of bacterial core members represent potential biocontrol agents. This study highlights the importance of management practices for sustaining beneficial microbiomes. Furthermore, it establishes a valuable resource of core-associated BCAs, offering promising avenues for the biological control of fungal pathogens.

柑橘是一种全球重要的水果作物，拥有独特的微生物群落，对维持柑橘健康和增强抗病性至关重要。虽然柑橘根和叶微生物组的结构和形成因素，包括植物检疫处理，已经有了很好的记录，但碳圈（果实表面）微生物组及其对植物检疫输入的响应仍然知之甚少。在本研究中，我们结合了培养独立（扩增子测序）和培养依赖技术，分析了三种柑橘宿主的柑橘圈微生物组及其对田间应用植物检疫处理（生物制剂和铜抗菌剂）的响应。尽管在变形菌门、厚壁菌门和担子菌门等优势类群的相对丰度上存在宿主特异性差异，但所有三种柑橘宿主都有一个核心微生物组，在水果样品中一致存在。铜处理对细菌多样性和组成有负面影响，而生物制品（壳聚糖、甜橙精油及其混合物）的负面影响很小或没有。真菌群落，包括潜在的病原体，似乎对治疗不太敏感。网络分析证实，与未处理或生物处理的样品相比，铜改变了微生物的相互作用，增加了细菌类群之间的互斥关系，而未处理或生物处理的样品以正相互作用为主。对同一样品的可培养菌群进行平行调查，确定了潜在的生物防治剂（bca）对炭疽菌（Colletotrichum gloeosporioides）和交替菌（Alternaria alternata）的作用。值得注意的是，与核心扩增子序列变异（asv）交叉比对的可培养bca显示，81.7 %的细菌核心成员代表潜在的生物防治剂。这项研究强调了管理实践对维持有益微生物群的重要性。此外，它建立了一个有价值的核心相关bca资源，为真菌病原体的生物防治提供了有希望的途径。

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引用次数: 0

c-di-GMP regulates the resistance of Pseudomonas aeruginosa to heat shock and aminoglycoside antibiotics by targeting the σ factor RpoH c-di-GMP通过调控σ因子RpoH调控铜绿假单胞菌对热休克和氨基糖苷类抗生素的耐药性

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-23 DOI: 10.1016/j.micres.2025.128347

Xinyi Huo , Lianying Mao , Chenyu Dong, Wenguang Yang, Heng Zhang, Lei Zhang

Cyclic di-GMP (c-di-GMP) is a second messenger molecule that is widely distributed in bacteria and plays various physiologically important regulatory roles through interactions with a variety of effector molecules. Sigma (σ) factors are the predominant transcription factors involved in transcription regulation in bacteria. While c-di-GMP has been shown to bind to a range of transcription factors, c-di-GMP-binding σ factors have never been reported before. In a c-di-GMP/σ factors binding screen, we identified the σ factor RpoH as a c-di-GMP-responsive transcription factor in Pseudomonas aeruginosa PAO1. We further show that the binding of c-di-GMP to RpoH inhibits binding of RpoH to the promoters of its target genes such as asrA and dnaK, thereby downregulating the expression of these genes and reducing the resistance of P. aeruginosa to heat shock and aminoglycoside antibiotics. RpoH from Escherichia coli, Burkholderia thailandensis and Agrobacterium tumefaciens are also capable of binding c-di-GMP, suggesting that c-di-GMP-mediated control of the activity of RpoH is conserved in members of Proteobacteria.

环二gmp （c-di-GMP）是广泛分布于细菌体内的第二信使分子，通过与多种效应分子相互作用，发挥着多种重要的生理调节作用。Sigma因子是细菌中参与转录调控的主要转录因子。虽然c-di-GMP已被证明与一系列转录因子结合，但c-di-GMP结合的σ因子从未被报道过。在c-di-GMP/σ因子结合筛选中，我们发现σ因子RpoH是铜绿假单胞菌PAO1中c-di-GMP应答转录因子。我们进一步发现，c-di-GMP与RpoH结合可抑制RpoH与其靶基因如asrA和dnaK启动子的结合，从而下调这些基因的表达，降低P. aeruginosa对热休克和氨基糖苷类抗生素的抗性。来自大肠杆菌、泰国伯克霍尔德菌和农杆菌的RpoH也能够结合c-di-GMP，这表明c-di-GMP介导的RpoH活性控制在变形菌门成员中是保守的。

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引用次数: 0

Metabolic control of cytokinesis by glucose cAMP–PKA signaling in fission yeast 葡萄糖cAMP-PKA信号对裂变酵母细胞分裂的代谢控制

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-19 DOI: 10.1016/j.micres.2025.128345

Antonio Marín-Castillo, Sergio León-Zaragoza, Alejandro Franco, Jero Vicente-Soler, Andrés Núñez, Teresa Soto, Marisa Madrid, José Cansado

Cytokinesis, the final step of cell division, must be precisely coordinated with the cellular metabolic status, yet the underlying regulatory mechanisms remain poorly understood. Here we show that in Schizosaccharomyces pombe, glucose signaling promotes cytokinesis via the evolutionarily conserved cAMP–PKA signaling pathway. Loss of the Pka1 catalytic subunit delays assembly and constriction of the contractile actomyosin ring (CAR), whereas constitutive PKA activation enhances CAR integrity and accelerates cytokinesis. Mechanistically, Pka1 downregulates the basal activity of the stress-activated MAPK Sty1 under glucose-rich conditions, thereby stabilizing the formin For3 and its nucleated actin cables, which collaborate to regulate CAR dynamics. Remarkably, cAMP–PKA signaling also facilitates cytokinesis through a parallel, actin cable–independent mechanism. Additionally, mitochondrial respiration contributes to cytokinesis in the presence of glucose through a PKA-independent pathway. These findings reveal a multilayered network that links carbon source metabolism to cytoskeletal organization and underscore the importance of tight PKA activity control for robust cell division.

细胞质分裂是细胞分裂的最后一步，必须与细胞代谢状态精确协调，但其潜在的调节机制尚不清楚。本研究表明，在pombe Schizosaccharomyces中，葡萄糖信号通过进化保守的cAMP-PKA信号通路促进细胞分裂。Pka1催化亚基的缺失延迟了收缩肌动球蛋白环（CAR）的组装和收缩，而组成型PKA激活增强了CAR的完整性并加速了细胞分裂。在机制上，Pka1在富含葡萄糖的条件下下调应激激活的MAPK Sty1的基础活性，从而稳定formin For3及其有核肌动蛋白电缆，这些电缆共同调节CAR动力学。值得注意的是，cAMP-PKA信号也通过平行的、肌动蛋白电缆无关的机制促进细胞分裂。此外，在葡萄糖存在的情况下，线粒体呼吸通过不依赖pka的途径促进细胞分裂。这些发现揭示了将碳源代谢与细胞骨架组织联系起来的多层网络，并强调了严格控制PKA活性对稳健细胞分裂的重要性。

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引用次数: 0

Corrigendum to “A molecular overview of the polymyxin-LPS interaction in the context of its mode of action and resistance development” [Microbiol. Res. 283 (2024) 127679] “多粘菌素- lps相互作用在其作用模式和耐药性发展背景下的分子概述”[微生物杂志]的更正。[Res. 283(2024) 127679]。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-09 DOI: 10.1016/j.micres.2025.128335

Indira Padhy, Sambit K. Dwibedy, Saswat S. Mohapatra

引用次数: 0

Dual roles of MWCNTs on plant growth and remediation efficiency during PGPR-assisted phytoremediation of Cd-Ni contaminated soil 在pgpr辅助镉镍污染土壤的植物修复中，MWCNTs对植物生长和修复效率的双重作用

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-10 DOI: 10.1016/j.micres.2025.128339

Wenqing Zhou, Xiaoxian Cai, Ke Chen, Lixue Zheng, Huijun Guan, Tianlong Hao, Jingjing Yang, Lihua Qi, Chunfeng Guan

As the main elements causing soil heavy metals (HMs) pollution, cadmium (Cd) and nickel (Ni) can cause irreversible harm to crops and ecosystems. Currently, research on plant growth-promoting rhizobacteria (PGPR)-assisted phytoremediation techniques for contaminated soil has received more attention. Meanwhile, multi-walled carbon nanotubes (MWCNTs) have also been explored for HMs pollution remediation in recent years due to their high specific surface area and strong adsorption. MWCNTs might improve phytoremediation efficiency of HMs-contaminated soil by directly immobilizing HMs and indirectly promoting plant growth, but less research has been devoted to the possible dual-enhancing roles of MWCNTs in PGPR-assisted phytoremediation process. Therefore, this study innovatively investigated the potential role of MWCNTs application in PGPR-assisted phytoremediation with Cd-Ni contaminated soil by rice. The results indicated that the presence of MWCNTs further improved the remediation efficiency of PGPR in assisting phytoremediation, reducing soil Cd^2 + and Ni²⁺ contents by 20.4 % and 13.7 %, respectively, superior to strain BT treatment individually. Scanning electron microscopy micrographs demonstrated that PGPR could attach to MWCNTs surface and be immobilized in MWCNTs. Meanwhile, MWCNTs application in PGPR-assisted phytoremediation could enhance rice survival under Cd and Ni stresses by stimulating antioxidant system and regulating Na⁺/K⁺ level in rice. Moreover, the increase in soil enzyme activities and relative abundance of beneficial microorganisms accelerated nitrogen and phosphorus nutrient cycling in the soil. In conclusion, MWCNTs might be used as adsorbent materials to directly immobilize Cd²⁺ and Ni²⁺ in soil, and also synergized with rice or PGPR to indirectly improve the phytoremediation efficiency of HMs.

镉（Cd）和镍（Ni）是造成土壤重金属污染的主要元素，对作物和生态系统造成不可逆转的危害。目前，植物促生根瘤菌（PGPR）辅助植物修复污染土壤的技术研究越来越受到重视。同时，近年来，多壁碳纳米管（MWCNTs）因其高比表面积和强吸附性也被探索用于HMs污染修复。MWCNTs可能通过直接固定HMs和间接促进植物生长来提高HMs污染土壤的植物修复效率，但关于MWCNTs在pgpr辅助植物修复过程中可能的双重增强作用的研究较少。因此，本研究创新性地探讨了MWCNTs在水稻镉镍污染土壤的pgpr辅助植物修复中的潜在作用。结果表明，MWCNTs的存在进一步提高了PGPR协助植物修复的修复效率，使土壤Cd2 +和Ni2+含量分别降低20.4 %和13.7 %，优于菌株BT单独处理。扫描电镜结果表明，PGPR可以附着在MWCNTs表面并固定在MWCNTs中。同时，在pgpr辅助植物修复中应用MWCNTs可通过刺激抗氧化系统和调节水稻Na+/K+水平，提高水稻在Cd和Ni胁迫下的存活率。此外，土壤酶活性和有益微生物相对丰度的增加加速了土壤氮磷养分循环。综上所述，MWCNTs可作为吸附材料直接固定土壤中的Cd2+和Ni2+，也可与水稻或PGPR协同作用，间接提高HMs的植物修复效率。

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引用次数: 0

Biologically functional and regulatory analysis of a two-component signal transduction system CgtSR1 in Corynebacterium glutamicum 谷氨酸棒状杆菌双组分信号转导系统CgtSR1的生物学功能及调控分析

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-10-09 DOI: 10.1016/j.micres.2025.128359

Tao Su , Qimiao Shi , Liyao Bai , Xueru Xu , Xueyan Li , Shanshan Li , Can Chen , Mengdie Hu

The two-component systems (TCSs) are crucial for bacterial adaptation to environmental stresses and growth conditions. In Corynebacterium glutamicum, a model organism of Corynebacteriales, 13 TCSs have been identified, but only five of them have been characterized previously. The ncgl0269-ncgl0268 gene cluster, annotated as a putative TCS (designated as CgtSR1), remains unexplored in terms of its regulatory role and mechanism. In this study, we revealed that CgtSR1 might regulate the expression of antimicrobial efflux transporters (including secondary transporters and primary transporters-ATP-binding cassette (ABC)) by transcriptomic analysis. EMSA experiments confirmed that CgtR1 directly binds to the promoter regions of three secondary transporter genes (ncgl0887, ncgl1020, and ncgl1445). Phenotypic assays demonstrated that the deletion of cgtSR1 increased susceptibility to gentamicin and spectinomycin, whereas its overexpression conferred resistance. Additionally, overexpression of cgtSR1 enhanced tolerance of cells to resorcinol and 2,4-dihydroxybenzoate. This study elucidates the regulatory network of CgtSR1 and deepens the understanding of TCS-mediated stress adaptation in C. glutamicum, providing a basis for further mechanistic investigations.

双组分系统（TCSs）对细菌适应环境胁迫和生长条件至关重要。谷氨酰胺棒状杆菌是棒状杆菌的一种模式生物，目前已鉴定出13个tcs，但仅有5个已被鉴定。ncgl0269-ncgl0268基因簇被标注为假定的TCS（指定为CgtSR1），其调控作用和机制尚不清楚。本研究通过转录组学分析发现，CgtSR1可能调控抗菌外排转运体（包括二级转运体和一级转运体- atp结合盒（ABC））的表达。EMSA实验证实，CgtR1直接结合3个二级转运基因（ncgl0887、ncgl1020和ncgl1445）的启动子区域。表型分析表明，cgtSR1的缺失增加了对庆大霉素和大观霉素的敏感性，而其过表达则赋予耐药性。此外，cgtSR1的过表达增强了细胞对间苯二酚和2,4-二羟基苯甲酸盐的耐受性。本研究阐明了CgtSR1的调控网络，加深了对tcs介导的谷氨酰胺胁迫适应的认识，为进一步的机制研究提供了基础。

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引用次数: 0

Lactococcus formosensis and its metabolite 4-acetamidobutanoic acid induced caspase-11 dependent myenteric neuronal pyroptosis in intractable functional constipation 台湾乳球菌及其代谢物4-乙酰氨基丁酸诱导难固性功能性便秘患者半胱天冬酶-11依赖性肌内神经元焦凋亡

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-03 DOI: 10.1016/j.micres.2025.128328

Xiaoqian Dong , Mengshi Chen , Haifeng Liu , Simin Zhou , Menglin Sun , Liwei Wang , Yuwei Li , Hao Zhang , Chen Xu , Bangmao Wang , Weilong Zhong

Intractable functional constipation (IFC), a severe form of chronic constipation characterized by slow transit and resistance to conventional treatments, posed a significant clinical challenge. Here, we identified Lactococcus formosensis (Lf), a Gram-positive bacterium prevalent in IFC patients, as a novel contributor to intestinal motility impairment. Clinically, IFC patients exhibited increased colonic mucosal colonization of Lf and significant myenteric neuronal loss and pyroptosis, particularly in excitatory choline acetyltransferase (ChAT)⁺ neurons, but not inhibitory neuronal nitric oxide synthase (nNOS)⁺ neurons. In mice, Lf and its supernatant impaired intestinal motility, reducing fecal water content, prolonging transit times, and inhibiting spontaneous contractions and maximum contractile force in isolated intestinal segments. RNA sequencing revealed that Lf disrupted neurochemical signaling, implicating neuronal damage in its pathogenic effects. Mechanistically, Lf and its supernatant selectively induced pyroptosis in ChAT⁺ neurons via caspase-1 activation. Metabolomic profiling identified 4-acetamidobutanoic acid (4-ABA) as a key metabolite shared between Lf supernatant and IFC patient feces. 4-ABA induced ChAT⁺ neuronal pyroptosis through a caspase-11-dependent pathway, further impairing intestinal motility, which was confirmed in Casp11⁻/⁻ mice. This study uncovered a previously unrecognized pathway of single microbiota-induced neuronal damage in IFC and provided a foundation for novel diagnostic and therapeutic strategies targeting gut microbiota-ENS interactions

顽固性功能性便秘（IFC）是一种严重的慢性便秘形式，其特点是转运缓慢且对常规治疗有耐药性，是一项重大的临床挑战。在这里，我们发现台湾乳球菌（Lf），一种在IFC患者中普遍存在的革兰氏阳性细菌，作为肠道运动障碍的新贡献者。在临床上，IFC患者表现出结肠粘膜Lf定植增加和明显的肌肠神经元丢失和焦亡，特别是在兴奋性胆碱乙酰转移酶(ChAT)+神经元中，但没有抑制性神经元一氧化氮合酶(nNOS)+神经元。在小鼠中，Lf及其上清液损害肠道运动，减少粪便含水量，延长运输时间，抑制离体肠段的自发收缩和最大收缩力。RNA测序显示，Lf破坏神经化学信号，暗示其致病作用中的神经元损伤。在机制上，Lf及其上清通过caspase-1激活选择性诱导ChAT+神经元焦亡。代谢组学分析发现，4-乙酰氨基丁酸（4-ABA）是Lf上清液和IFC患者粪便共享的关键代谢物。4-ABA通过caspase-11依赖性途径诱导ChAT+神经元焦亡，进一步损害肠道运动能力，这在Casp11（毒血症）/⁻（毒血症）中得到证实。本研究揭示了IFC中单一微生物群诱导的神经元损伤的一个以前未被认识的途径，并为针对肠道微生物群- ens相互作用的新型诊断和治疗策略提供了基础

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引用次数: 0

The oxidative stress-related peroxiredoxin Tsa1b of Candidozyma (Candida) auris contributes to virulence and infection 假丝酵母（念珠菌）耳的氧化应激相关的过氧化物还氧化物蛋白Tsa1b有助于毒力和感染。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-25 DOI: 10.1016/j.micres.2025.128353

Maialen Areitio , Oier Rodriguez-Erenaga , Leire Aparicio-Fernandez , Lucía Abio-Dorronsoro , Leire Martin-Souto , Uxue Perez-Cuesta , Idoia Buldain , Beñat Zaldibar , Alba Ruiz-Gaitan , Javier Pemán , Salomé LeibundGut-Landmann , Aitor Rementeria , Aitziber Antoran , Andoni Ramirez-Garcia

The difficulty of accurately identifying Candidozyma auris (formerly Candida auris) and the high resistance rates presented have increased the concern in the healthcare setting. Due to this, the aim of this study was to analyse the fungal response to oxidative stress. To achieve this goal, gene and protein expression were examined using qPCR and two-dimensional electrophoresis, respectively, peroxiredoxin Tsa1b being found to be upregulated under oxidative stress. Subsequently, the significance of Tsa1b was next investigated by characterizing the C. auris Δtsa1b and C. auris Δtsa1b::TSA1B strains generated by CRISPR-Cas9. The findings demonstrated that the Δtsa1b strain was more susceptible to oxidative and cell wall stressors than the wild-type strain, which was consistent with an increase in the cell wall β-glucan amounts when grown in the presence of oxidative stress. Importantly, Tsa1b has also been detected as an antigen by patient sera. Furthermore, the Δtsa1b strain was also more vulnerable to the presence of dendritic cells and bone marrow-derived macrophages. Finally, in vivo infections performed in Galleria mellonella and mice showed a slower progression of the disease in animals infected with the mutant strain. In conclusion, the peroxiredoxin Tsa1b has been identified as a potential candidate to be studied as a virulence factor implicated in the oxidative stress response of C. auris. These findings advance the knowledge of the pathobiology of C. auris and point out the potential of Tsa1b for the development of new diagnostic and therapeutic approaches.

准确识别耳念珠菌（原耳念珠菌）的困难和呈现的高耐药率增加了卫生保健机构的关注。因此，本研究的目的是分析真菌对氧化应激的反应。为了实现这一目标，我们分别使用qPCR和双向电泳检测了基因和蛋白的表达，发现过氧化氧还蛋白Tsa1b在氧化应激下上调。随后，通过对CRISPR-Cas9生成的C. auris Δtsa1b和C. auris Δtsa1b:: Tsa1b菌株进行表征，进一步研究Tsa1b的意义。结果表明，Δtsa1b菌株比野生型菌株更容易受到氧化和细胞壁应激源的影响，这与在氧化应激存在下生长时细胞壁β-葡聚糖含量增加一致。重要的是，Tsa1b也可以作为抗原在患者血清中检测到。此外，Δtsa1b菌株也更容易受到树突状细胞和骨髓源性巨噬细胞的存在。最后，在小鼠和mellonella Galleria中进行的体内感染显示，感染突变菌株的动物的疾病进展较慢。综上所述，过氧化物还氧蛋白Tsa1b已被确定为一个潜在的候选毒力因子，与金黄色葡萄球菌的氧化应激反应有关。这些发现促进了对金黄色葡萄球菌病理生物学的认识，并指出了Tsa1b在开发新的诊断和治疗方法方面的潜力。

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引用次数: 0

Advances in the interaction between gut microbiota and post-translational modifications of proteins 肠道微生物群与蛋白质翻译后修饰相互作用的研究进展。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-24 DOI: 10.1016/j.micres.2025.128349

Lingling Zhao , Hengqi He , Zhaohui Luo , Liwen Jin , Bo Xiao

Gut microbiota intricately regulate host cells through diverse mechanisms, with numerous pathways involving protein post-translational modifications (PTMs). This review comprehensively summarizes the impacts of the gut microbiota on various PTMs in host cells. It elaborates on how these modifications contribute to the development of host diseases, delving into mediating pathways, including changes in microbial metabolites, key enzymes, and the microenvironment. Conversely, it also explores how PTMs influence gut microbiota abundance. To overcome current research limitations, such as narrow perspectives and monotonous methods, novel strategies are proposed. Applying single-cell/spatial omics could reveal cell-type-specific and spatial PTM responses to microbial signals, while integrating AI algorithms with traditional experiments may predict PTM regulatory networks using microbial and host data. These strategies aim to expand research approaches and promote the clinical translation of findings in this field.

肠道微生物群通过多种机制复杂地调节宿主细胞，其中包括许多涉及蛋白质翻译后修饰（PTMs）的途径。本文综述了肠道菌群对宿主细胞中各种ptm的影响。它详细阐述了这些修饰如何促进宿主疾病的发展，深入研究了介导途径，包括微生物代谢物、关键酶和微环境的变化。相反，它还探讨了PTMs如何影响肠道微生物群的丰度。为了克服目前研究的局限，如狭隘的视角和单一的方法，提出了新的策略。应用单细胞/空间组学可以揭示细胞类型特异性和空间PTM对微生物信号的响应，而将AI算法与传统实验相结合可以利用微生物和宿主数据预测PTM调控网络。这些策略旨在拓展研究方法，促进该领域研究成果的临床转化。

引用次数: 0

DL-propargylglycine reverses beta-lactam resistance in Streptococcus agalactiae dl -丙基甘氨酸逆转无乳链球菌的β -内酰胺耐药性

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2026-01-01 Epub Date: 2025-09-24 DOI: 10.1016/j.micres.2025.128350

Xuan-wei Chen , Xiao-lin Zhang , Zhi-han Wang , Jia-yao Wu , Si-qi Tian , Zi-long Huang , Bo Peng

Streptococcus agalactiae (GBS) is a major pathogen causing severe infections in human and economic loss in animal farming, where β-lactams remain first-line therapy. However, emerging β-lactam resistance, including WHO-priority penicillin-resistant strains, threatens clinical efficacy, creating an urgent need for resistance-breaking adjuvants. In this study, we demonstrate that DL-Propargylglycine (PAG), an inhibitor of cystathionine-γ-lyase inhibitor, exclusively synergizes with β-lactams to reverse resistance in ampicillin-resistant GBS (AR-GBS) and other streptococci, overcoming tolerance in persisters and biofilms. Mechanistically, PAG potentiates antibiotic lethality through dual pathways: metabolic activation via enhanced central carbon metabolism for ROS production and cell envelope remodeling via concurrent downregulation of peptidoglycan biosynthesis genes and upregulation of capsular polysaccharide synthesis. This disrupts cell wall architecture, increases membrane permeability and accelerates antibiotic influx. While in vivo therapeutic efficacy in zebrafish was limited, PAG represents an adjuvant that overcomes β-lactam resistance through metabolic and membrane remodeling, paving the way for optimized derivatives.

无乳链球菌（GBS）是造成人类严重感染和畜牧业经济损失的主要病原体，β-内酰胺类药物仍然是畜牧业的一线治疗方法。然而，新出现的β-内酰胺耐药，包括世卫组织重点关注的青霉素耐药菌株，威胁到临床疗效，因此迫切需要破药佐剂。在这项研究中，我们证明了dl -丙氨酸甘氨酸（PAG）是一种半胱硫氨酸-γ-裂解酶抑制剂的抑制剂，它与β-内酰胺协同作用，逆转耐氨苄西林GBS （AR-GBS）和其他链球菌的耐药性，克服持久性和生物膜的耐受性。从机制上说，PAG通过双重途径增强抗生素的致死率：通过增强ROS产生的中央碳代谢来激活代谢，通过同时下调肽聚糖生物合成基因和上调荚膜多糖合成基因来重塑细胞包膜。这会破坏细胞壁结构，增加细胞膜通透性，加速抗生素的流入。虽然斑马鱼体内的治疗效果有限，但PAG代表了一种通过代谢和膜重塑克服β-内酰胺抗性的佐剂，为优化衍生物铺平了道路。

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引用次数: 0