Cell Surface最新文献

Pap1 is an adhesin involved in the interaction of Sporothrix schenckii and Sporothrix brasiliensis with the host Pap1是一种粘附素，参与申克孢子丝菌和巴西孢子丝菌与宿主的相互作用

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2026-06-01 Epub Date: 2025-12-08 DOI: 10.1016/j.tcsw.2025.100164

Leonardo Padró-Villegas , Julieta I. Aguilera-Domínguez , Luz A. López-Ramírez , Manuela Gómez-Gaviria , Iván Martínez-Duncker , Laura C. García-Carnero , Joaquín O. Chávez-Santiago , Patricia Ponce-Noyola , Héctor M. Mora-Montes

Sporothrix schenckii and Sporothrix brasiliensis are causative agents of sporotrichosis, a mycosis that affects humans and other mammals. Adhesins are considered among the primary virulence factors of these species; however, their molecular identities are currently scarce. Here, we generated silenced mutant strains in PAP1, encoding a peptidorhamnomannan-associated protein, in both fungal species and compared their phenotypical characterization. PAP1-silenced mutants had normal growth, dimorphism, and morphology, suggesting the gene is not essential. The silenced strains showed defects in adhesion to HeLa cells, laminin, fibronectin, fibrinogen, type-I collagen, and type-II collagen. The S. schenckii silenced mutants showed a significant reduction in the adhesion to elastin, whilst the S. brasiliensis mutant showed impaired ability to bind thrombospondin 1 and to form biofilms. Both sets of PAP1-silenced mutants displayed defects in the cell wall composition, with reduced levels of cell wall rhamnose. The S. schenckii mutants showed a compensatory mechanism increasing cell wall mannose content, while the S. brasiliensis mutants increased cell wall protein levels in compensation to PAP1 silencing. Both mutant sets changed their ability to stimulate cytokine production in human peripheral blood mononuclear cells and monocyte-derived macrophages. In addition, phagocytosis of S. schenckii PAP1-silenced strains was significantly increased, while the S. brasiliensis PAP1-silenced strains were poorly phagocytosed. Finally, PAP1 silencing affected virulence in both species.

These results suggest that S. schenckii and S. brasiliensis PAP1 code for a protein with adhesive properties to different ligands. This is a cell wall protein that contributes to Sporothrix virulence and the interaction with immune cells.

申克孢子丝菌和巴西孢子丝菌是孢子毛病的病原体，孢子毛病是一种影响人类和其他哺乳动物的真菌病。粘附素被认为是这些物种的主要毒力因素之一；然而，他们的分子身份目前是稀缺的。在这里，我们在这两种真菌中产生了编码肽hamnomannan相关蛋白的PAP1沉默突变株，并比较了它们的表型特征。pap1沉默突变体具有正常的生长、二态性和形态，表明该基因不是必需的。沉默菌株对HeLa细胞、层粘连蛋白、纤维连接蛋白、纤维蛋白原、i型胶原和ii型胶原的粘附存在缺陷。申氏葡萄球菌沉默突变体对弹性蛋白的粘附能力显著降低，而巴西葡萄球菌突变体对凝血反应蛋白1的结合能力和形成生物膜的能力受损。两组pap1沉默突变体在细胞壁组成上都表现出缺陷，细胞壁鼠李糖含量降低。申氏葡萄球菌突变体表现出增加细胞壁甘露糖含量的补偿机制，而巴西葡萄球菌突变体则表现出增加细胞壁蛋白水平的补偿机制。两组突变体都改变了它们刺激人外周血单核细胞和单核细胞源性巨噬细胞产生细胞因子的能力。此外，申克沙门氏菌pap1沉默菌株的吞噬能力显著增强，而巴西沙门氏菌pap1沉默菌株的吞噬能力较差。最后，PAP1沉默影响了两个物种的毒力。这些结果表明，申氏孢子和巴西孢子的PAP1编码了一种对不同配体具有粘附特性的蛋白质。这是一种细胞壁蛋白，有助于孢子菌的毒力和与免疫细胞的相互作用。

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引用次数: 0

Rho2-dependent cell wall remodeling boosts the fungistatic activity of manogepix against Aspergillus fumigatus rho2依赖性细胞壁重塑增强了mangepix对烟曲霉的抑菌活性

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2026-06-01 Epub Date: 2025-12-14 DOI: 10.1016/j.tcsw.2025.100166

Sean Brazil , Isabel Kopp-Fouquet , Samuel Zen Kai Yap , Michael Carty , Johannes Wagener

Fosmanogepix is a new antifungal agent currently undergoing phase 3 clinical trials. Its active moiety, manogepix, inhibits Gwt1 which is an enzyme essential for the assembly and attachment of glycosylphosphatidylinositol anchors to cell wall proteins. Manogepix has a strong fungistatic activity against most human pathogenic fungal species. Here we characterized the activity of manogepix against the major human pathogenic mold Aspergillus fumigatus. We show that manogepix susceptibility is linked to the expression of gwt1, the gene encoding Gwt1, thereby demonstrating that overexpression of gwt1 can confer resistance. In agreement with a previous study conducted with a different fungal pathogen, we observed an increase of cell well chitin after manogepix treatment. Using a luciferase-based reporter assay, we show that manogepix activates the cell wall integrity stress response pathway. However, manogepix only occasionally causes cell lysis. Mutants that lack the cell wall stress sensor Wsc1 or the Rho GTPase Rho4, which is important for septum formation, are slightly more susceptible to manogepix. In contrast, mutants lacking the Rho GTPase Rho2 or, to a lesser extent, the cell wall stress sensor MidA, both of which are essential for A. fumigatus to survive attacks from granulocytes and other forms of cell wall stress, grow better than wild-type when exposed to manogepix. We show that both mutants, especially Δrho2 but also ΔmidA, fail to upregulate cell wall chitin to wild-type-like levels in response to manogepix. These results implicate a role for the Rho2-dependent stress response in the fungistatic activity of manogepix against A. fumigatus.

fosmangepix是一种新的抗真菌药物，目前正在进行3期临床试验。其活性部分manogepix抑制Gwt1， Gwt1是糖基磷脂酰肌醇锚定在细胞壁蛋白上组装和附着所必需的酶。对大多数人类病原真菌具有较强的抑菌活性。在这里，我们描述了mangepix对主要人类致病霉菌烟曲霉的活性。我们发现mangepix的易感性与编码gwt1的基因gwt1的表达有关，从而证明gwt1的过表达可以赋予抗性。在与先前的研究进行了不同的真菌病原体一致，我们观察到细胞孔几丁质的增加后，mangepix处理。使用基于荧光素酶的报告实验，我们发现manogepix激活细胞壁完整性应激反应途径。然而，manogepix只是偶尔引起细胞裂解。缺乏细胞壁应力传感器Wsc1或Rho GTPase Rho4的突变体（这对隔膜的形成很重要）更容易发生脱位。相比之下，缺乏Rho GTPase Rho2的突变体，或者在较小程度上缺乏细胞壁应激传感器MidA，这两种突变体都是烟状芽孢杆菌在粒细胞和其他形式的细胞壁应激中生存所必需的，当暴露于mangepix时，它们比野生型生长得更好。我们发现，这两种突变体，尤其是Δrho2和ΔmidA，都不能将细胞壁几丁质上调到野生型水平，以响应mangepix。这些结果暗示了rho2依赖的应激反应在马诺皮对烟曲霉的抑菌活性中的作用。

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引用次数: 0

Emerging evidence for a multitude of mechanisms and factors that determine amphotericin B resistance in pathogenic fungi 在致病真菌中决定两性霉素B耐药性的多种机制和因素的新证据

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2026-06-01 Epub Date: 2026-01-03 DOI: 10.1016/j.tcsw.2026.100168

Anshu Chauhan , Neil A.R. Gow , Rajendra Prasad

The fungicidal polyene amphotericin B (AMB) is the oldest antifungal for the treatment of systemic infections, and it remains a critical broad-spectrum therapeutic option, despite its well-documented nephrotoxicity. In many countries use of conventional amphotericin deoxycholate has been eclipsed by the introduction in the 1990s of the considerably more expensive but much less nephrotoxic lipid formulations. Amphotericin B is valued for its strong fungicidal activity at low doses and its rarity of resistance, as resistance usually carries a significant fitness cost for fungi. However, emerging pathogens such as Candidozyma auris (formerly Candida auris) often exhibit significant resistance levels, with >30 % of clinical isolates showing reduced AMB susceptibility. Like azoles, AMB targets ergosterol in the fungal membrane, but unlike azoles, it binds pre-existing ergosterol; however, reduced ergosterol alone does not fully explain emerging resistance. Recent studies have revealed novel, often sterol-independent mechanisms related to sphingolipid content that drive AMB resistance, particularly in yeast species. These findings broaden our understanding and emphasize critical knowledge gaps. We review these evolving mechanisms and the pressing need for further research into the evolution of AMB resistance pathways.

抗菌多烯两性霉素B （AMB）是治疗全系统感染的最古老的抗真菌药物，尽管其肾毒性有充分的证据，但它仍然是一个关键的广谱治疗选择。在许多国家，由于20世纪90年代采用了相当昂贵但肾毒性小得多的脂质制剂，传统两性霉素去氧胆酸盐的使用已经黯然失色。两性霉素B因其在低剂量下具有很强的杀真菌活性和罕见的耐药性而受到重视，因为耐药性通常对真菌具有显著的适应性成本。然而，新出现的病原体，如耳念珠菌（原耳念珠菌）往往表现出显著的耐药水平，30%的临床分离株表现出对AMB的敏感性降低。与唑类药物一样，AMB靶向真菌膜中的麦角甾醇，但与唑类药物不同的是，AMB与预先存在的麦角甾醇结合；然而，麦角甾醇的减少并不能完全解释新出现的耐药性。最近的研究揭示了与鞘脂含量相关的新颖的，通常不依赖于固醇的机制，这些机制驱动AMB耐药性，特别是在酵母物种中。这些发现拓宽了我们的理解，强调了关键的知识差距。我们回顾了这些进化机制，并迫切需要进一步研究AMB抗性途径的进化。

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引用次数: 0

Functions of the cell wall polysaccharide schizophyllan during vegetative growth of Schizophyllum commune 裂肉属植物营养生长过程中细胞壁多糖的作用

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2026-06-01 Epub Date: 2025-12-16 DOI: 10.1016/j.tcsw.2025.100167

Fleur E.L. Kleijburg , Ella M. Schunselaar , Adil A. Safeer , Ajit K. Bishoyi , Marc Baldus , Han A.B. Wösten

Schizophyllan, a β-(1,3)(1,6)-glucan, is part of the cell wall of the mushroom-forming fungus Schizophyllum commune and is also released into the culture medium. It has various commercial applications but the natural function of schizophyllan during growth of S. commune is largely unknown. The S. commune strain H4-8A was grown on minimal medium (MM-N) and medium containing 10-fold more KH₂PO₄/K₂HPO₄ buffer (MM-NKP). The addition of extra buffer resulted in a 4.2-fold decrease in water-soluble schizophyllan and a 8.8-fold decrease in rigid schizophyllan in the cell wall. This decrease in schizophyllan was associated with a 3.7 fold lower tensile strength and a 2.5-fold higher elasticity of the mycelium. Moreover, spores of S. commune, as well as cells of Escherichia coli and Pseudomonas putida, showed increased survival against heat treatment and freeze-thawing, and had a longer shelf-life in the presence of schizophyllan. Also, schizophyllan can be metabolized by S. commune but the tested bacteria were unable to do so. Together, schizophyllan provides rigidity to the cell wall, protects S. commune against temperature stress, and can be used as an external carbon storage. It may also form a selective barrier around the hyphae, protecting S. commune against attack by bacteria.

Schizophyllan是一种β-(1,3)(1,6)-葡聚糖，是蘑菇形成真菌Schizophyllum commune细胞壁的一部分，也被释放到培养基中。它有各种各样的商业应用，但裂叶植物在生长过程中的自然功能在很大程度上是未知的。公社S. H4-8A菌株在最小培养基（MM-N）和含有10倍KH2PO4/K2HPO4缓冲液（MM-NKP）的培养基上生长。添加额外的缓冲液导致细胞壁中水溶性裂叶纲领物减少4.2倍，刚性裂叶纲领物减少8.8倍。裂叶植物的这种减少与菌丝的拉伸强度降低3.7倍和弹性提高2.5倍有关。此外，葡萄球菌孢子以及大肠杆菌和恶臭假单胞菌的细胞在热处理和冻融条件下的存活率更高，在裂叶植物存在下的保质期更长。另外，裂叶植物也能被s.g rcommune代谢，但被试细菌却不能。裂叶植物共同提供细胞壁的刚性，保护s.c org免受温度胁迫，并且可以用作外部碳储存。它也可能在菌丝周围形成一个选择性屏障，保护S. commune免受细菌的攻击。

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引用次数: 0

AmpC β-lactamases: A key to antibiotic resistance in ESKAPE pathogens AmpC β-内酰胺酶：ESKAPE病原菌耐药的关键

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2025-12-01 Epub Date: 2025-09-22 DOI: 10.1016/j.tcsw.2025.100154

Deeksha Pandey , Isha Gupta , Dinesh Gupta

Background

AmpC β-lactamases (blaAmpC) are essential drivers of antimicrobial resistance (AMR) in ESKAPE pathogens, bacteria that cause hospital-acquired infections. Understanding AmpC enzymes is essential for uncovering resistance mechanisms and guiding antimicrobial strategies. We analyzed blaAmpC presence, genomic location, copy number, sequence variability, and evolutionary traits in ESKAPE pathogens.

Results

We identified 1790 AmpC enzymes in 4713 complete genomes, classified into nine enzyme groups. Consistent with known taxonomic profiles, no class C β-lactamases were detected in Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecium). Acinetobacter baumannii exhibited the highest occurrence of class C β-lactamases, with Enterobacter spp. showing the second highest prevalence, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. The largest enzyme group, ADC was restricted to A. baumannii; similarly, ACC, ACT, CMH, and MIR to Enterobacter spp.; and PDC and PIB to P. aeruginosa. Phylogenetic analysis showed divergence among some groups and closer evolutionary relationships in others. Functional Motif analysis revealed conserved catalytic residues across all groups except PIB. Instead of the canonical YXN and KTG motifs, PIB contains YST and AQG variants, respectively. Because of these variations, PIB's ability to bind cephalosporins decreases while enhancing their activity against carbapenems.

Conclusions

We identified 1790 AmpC enzymes in nine distinct groups across ESKAPE pathogens, with species-specific distribution patterns and notable absence in Gram-positive bacteria. The PIB enzyme group demonstrated unique motif variants (YST/AQG) conferring carbapenem resistance, while other groups maintained conserved catalytic motifs. Phylogenetic analysis revealed evolutionary divergence and horizontal gene transfer potential, emphasizing the need for targeted therapeutic approaches against AmpC-mediated resistance.

背景dampc β-内酰胺酶（blaAmpC）是ESKAPE病原体（引起医院获得性感染的细菌）中抗菌素耐药性（AMR）的重要驱动因素。了解AmpC酶对于揭示耐药机制和指导抗菌策略至关重要。我们分析了blaAmpC在ESKAPE病原体中的存在、基因组位置、拷贝数、序列变异性和进化特征。结果在4713个完整基因组中鉴定出1790个AmpC酶，分为9个酶群。与已知的分类特征一致，革兰氏阳性菌（金黄色葡萄球菌和屎肠球菌）中未检测到C类β-内酰胺酶。C类β-内酰胺酶的发生率以鲍曼不动杆菌最高，其次为肠杆菌，其次为铜绿假单胞菌和肺炎克雷伯菌。最大的酶群ADC仅限于鲍曼不动杆菌；类似地，ACC， ACT， CMH和MIR对肠杆菌；铜绿假单胞菌的PDC和PIB。系统发育分析表明，一些群体之间存在分歧，而另一些群体的进化关系更密切。功能基序分析显示，除PIB外，所有基团都有保守的催化残基。PIB分别包含YST和AQG变体，而不是典型的YXN和KTG基序。由于这些变化，PIB结合头孢菌素的能力下降，同时增强其对碳青霉烯类的活性。结论在ESKAPE病原菌的9个不同类群中鉴定出1790种AmpC酶，具有种特异性分布模式，在革兰氏阳性菌中明显缺失。PIB酶组显示出独特的基序变异（YST/AQG），赋予碳青霉烯抗性，而其他组保持保守的催化基序。系统发育分析揭示了进化差异和水平基因转移潜力，强调了针对ampc介导的耐药性的靶向治疗方法的必要性。

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引用次数: 0

Growth conditions shape the proteome and diversity of Neurospora crassa extracellular vesicles 生长条件塑造粗神经孢子虫细胞外囊泡的蛋白质组和多样性

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2025-12-01 Epub Date: 2025-09-12 DOI: 10.1016/j.tcsw.2025.100152

Daniel A. Salgado-Bautista, Meritxell Riquelme

Extracellular vesicles (EVs) are nanosized, lipid bilayer-enclosed particles secreted by all living organisms. While EV research has primarily focused on mammalian systems, fungal EVs are gaining attention for their biological significance. Here, we investigated how growth conditions influence the protein cargo of EVs produced by Neurospora crassa, a non-pathogenic filamentous fungus and well-established model organism. EVs were isolated from cultures grown on glucose for 16 h (G16) and on sucrose for 16 (S16) and 24 h (S24). Dynamic light scattering (DLS) revealed similar size distributions for S16 and S24 EVs (24–165 nm), whereas G16 EVs exhibited a broader range (32–825 nm). Across all conditions, particles <50 nm were detected, potentially corresponding to mitochondrial-derived vesicles (MDVs) or exomeres, EV subtypes described in mammalian systems. Proteomic profiling identified 682 proteins in G16, 668 in S16, and a reduced set of 367 proteins in S24. Regardless of condition, EVs were enriched in proteins related to cell wall remodeling, protein synthesis, and carbohydrate metabolism. A high proportion of intracellular proteins confirms that fungal EVs participate in unconventional secretion. In addition, the detection of proteins involved in vesicle biogenesis and trafficking suggests that EV formation may also involve the classical secretory pathway. These findings demonstrate that EV composition and biogenesis in N. crassa are modulated by growth conditions and highlight the importance of physiological context in fungal EV research. Notably, the data reveal a diversity of EV types, including forms potentially unrelated to exosomes, expanding our understanding of fungal EV complexity.

细胞外囊泡（EVs）是由所有生物分泌的纳米级脂质双层封闭颗粒。虽然EV研究主要集中在哺乳动物系统，但真菌EV因其生物学意义而受到关注。在这里，我们研究了生长条件如何影响粗神经孢子菌（一种非致病性丝状真菌和成熟的模式生物）产生的电动汽车的蛋白质货物。从葡萄糖培养16 h （G16）、蔗糖培养16 h （S16）和24 h （S24）中分离出ev。S16和S24电动汽车的动态光散射（DLS）尺寸分布相似（24 ~ 165 nm），而G16电动汽车的动态光散射范围更广（32 ~ 825 nm）。在所有条件下，检测到50 nm的颗粒，可能对应于线粒体衍生囊泡（mdv）或外显子，哺乳动物系统中描述的EV亚型。蛋白质组学分析在G16中鉴定了682个蛋白，在S16中鉴定了668个蛋白，在S24中鉴定了367个蛋白。无论在何种情况下，EVs都富含与细胞壁重塑、蛋白质合成和碳水化合物代谢相关的蛋白质。高比例的细胞内蛋白证实真菌EVs参与非常规分泌。此外，对参与囊泡生物发生和运输的蛋白质的检测表明，EV的形成也可能涉及经典的分泌途径。这些研究结果表明，生长条件可调节草单胞菌的组成和生物发生，并强调了生理环境在真菌EV研究中的重要性。值得注意的是，这些数据揭示了EV类型的多样性，包括可能与外泌体无关的形式，扩大了我们对真菌EV复杂性的理解。

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引用次数: 0

Salmonella encodes murein lipoproteins differing in the anchoring to peptidoglycan and intermolecular association 沙门氏菌编码的小鼠脂蛋白在肽聚糖锚定和分子间结合方面存在差异

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2025-12-01 Epub Date: 2025-11-15 DOI: 10.1016/j.tcsw.2025.100161

Marcos Peñalver , Juan J. Cestero , Alberto Paradela , Felipe Cava , Francisco García-del Portillo

Murein lipoprotein (Lpp), also known as Braun's lipoprotein, stabilizes the cell wall of Escherichia coli by covalently tethering the outer membrane to the peptidoglycan (PG). Unlike E. coli, Salmonella enterica serovar Typhimurium encodes two murein lipoproteins, LppA and LppB, with LppB bearing an unusual C-terminal sequence, -RICK_COOH. Here, we investigated how LppA and LppB bind to the PG. Both lipoproteins were detected in pure PG material in a ∼ 400:1 LppA:LppB ratio with some LppB molecules forming a cysteine 78 (C78)-C78 intermolecular disulphide bridge. LppA and LppB anchor covalently to uncross-linked and cross-linked muropeptides. However, unlike LppA, which binds to 4,3- and 3,3-cross-linked muropeptides, LppB shows preferred binding to 4,3-cross-linked muropeptides. Mass spectrometry data revealed O-methylation at the terminal K79 residue in some PG-bound LppB molecules. The apparent selective anchoring of LppB to the PG and the K79 modification require the presence of the C78 residue. Anchoring of LppB to PG is mediated by the L,D-transpeptidase LdtB. A survey in more than 158,000 Salmonella genomes identified up to 31 murein Lpp variants differing in the C-terminal region that cluster in three phylogenetic groups. Most serovars of S. enterica subspecies enterica, responsible for infections in warm blooded animals, encode two or even three murein Lpp variants. Altogether, our data are consistent with subtle differences in the mode that LppB anchors to the PG and uncover an unprecedented diversity of murein lipoproteins within the Salmonella genus. The possibility that this variability evolved as strategy to evade host innate immunity, is also discussed.

鼠蛋白脂蛋白（Lpp），也被称为博朗氏脂蛋白，通过将外膜与肽聚糖（PG）共价系在一起来稳定大肠杆菌的细胞壁。与大肠杆菌不同，肠炎沙门氏菌血清型鼠伤寒沙门氏菌编码两种小鼠脂蛋白LppA和LppB，其中LppB含有一个不寻常的c端序列-RICKCOOH。在此，我们研究了LppA和LppB如何与PG结合。两种脂蛋白在纯PG材料中以约400:1的比例被检测到，一些LppB分子形成半胱氨酸78 (C78)-C78分子间二硫桥。LppA和LppB共价锚定在非交联和交联的多肽上。然而，与LppA结合4,3-和3,3-交联多肽不同，LppB更倾向于与4,3-交联多肽结合。质谱数据显示，在一些pg结合的LppB分子中，末端K79残基存在o -甲基化。LppB在PG上的明显选择性锚定和K79修饰需要C78残基的存在。LppB锚定在PG上是由L， d转肽酶LdtB介导的。一项对超过158,000个沙门氏菌基因组的调查确定了多达31个在c端区域不同的鼠Lpp变体，这些变体聚集在三个系统发育组中。引起温血动物感染的肠球菌亚种肠球菌的大多数血清型编码两个甚至三个鼠蛋白Lpp变体。总之，我们的数据与LppB锚定在PG上的模式的细微差异是一致的，并揭示了沙门氏菌属中小鼠脂蛋白的前所未有的多样性。还讨论了这种变异性作为逃避宿主先天免疫的策略而进化的可能性。

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引用次数: 0

Revealing structure and shaping priorities in plant and fungal cell wall architecture via solid-state NMR 通过固态核磁共振揭示植物和真菌细胞壁结构的结构和塑造优先级

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2025-12-01 Epub Date: 2025-10-31 DOI: 10.1016/j.tcsw.2025.100159

Peng Xiao , Priya Sahu , Sarah A. Pfaff , Ankur Ankur , Yohara K. Ranasinghe , Neil A.R. Gow , Jean-Paul Latgé , Daniel J. Cosgrove , Tuo Wang

Plant and fungal cell walls are essential for growth, adaptation, and survival, with their intricate architectures dictating both resistance to stress and susceptibility to antifungal or biomass-degrading strategies. Understanding how these walls are built, remodeled, and function at the molecular level is therefore central to both clinical and biotechnological applications. Solid-state nuclear magnetic resonance (ssNMR) has emerged as a uniquely powerful tool for this purpose, as it reveals the structure, dynamics, and interactions of intact biopolymers without disrupting their native organization. Using this approach, recent studies have shown how structural polymorphism, polymer-polymer interactions, and species-specific remodeling govern mechanical integrity, drug resistance, and stress adaptation. Applications highlighted here include lignin-carbohydrate packing during plant stem maturation, fungal wall reorganization under treatment by wall-targeting antifungals such as echinocandin and nikkomycin, and the functional diversity of glucans, chitins, and mannans. Together, these insights uncover conserved principles of polymer assembly across kingdoms while informing new opportunities for antifungal development and biomass utilization. Ongoing advances in sensitivity and resolution are expected to broaden the reach of ssNMR and further accelerate its role in linking structural heterogeneity to biosynthetic complexity and biological function.

植物和真菌细胞壁对生长、适应和生存至关重要，它们复杂的结构决定了它们对压力的抵抗力和对抗真菌或生物量降解策略的敏感性。因此，了解这些壁是如何在分子水平上构建、重塑和发挥作用的，对于临床和生物技术应用都是至关重要的。固态核磁共振（ssNMR）已经成为实现这一目的的独特有力的工具，因为它揭示了完整生物聚合物的结构、动力学和相互作用，而不会破坏它们的天然组织。利用这种方法，最近的研究显示了结构多态性、聚合物-聚合物相互作用和物种特异性重塑如何控制机械完整性、耐药性和应激适应。这里强调的应用包括植物茎成熟过程中的木质素-碳水化合物包装，壁靶抗真菌剂（如棘白菌素和尼克霉素）处理下的真菌壁重组，以及葡聚糖、几丁质和甘露聚糖的功能多样性。总之，这些见解揭示了跨王国聚合物组装的保守原理，同时为抗真菌开发和生物质利用提供了新的机会。灵敏度和分辨率的持续进步有望扩大ssNMR的范围，并进一步加速其在将结构异质性与生物合成复杂性和生物学功能联系起来方面的作用。

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引用次数: 0

Bacteriophages as an alternative strategy for the treatment of drug resistant bacterial infections: Current approaches and future perspectives 噬菌体作为治疗耐药细菌感染的替代策略：目前的方法和未来的展望

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2025-12-01 Epub Date: 2025-07-03 DOI: 10.1016/j.tcsw.2025.100149

Abayeneh Girma

A persistent increase in antimicrobial resistance presents a significant danger to global public health. The application of bactericidal phages that do not interfere with the body's natural flora becomes a promising approach to alternative treatments. This section offers an in-depth examination of the use of bacteriophage therapy in both laboratory and human trials for the treatment of specific bacterial infections. The benefits and hurdles of increasing the use of bacteriophages as a supplemental or alternative treatment for bacterial infections resistant to antibiotics are examined. The use of highly adaptable bacteriophage populations, combined with antibiotic chemical compounds, as molecular tools to combat rapidly evolving pathogenic bacteria in the host environment, presents significant virologic complexities. Pre-clinical studies, isolated clinical reports and a few randomized clinical trials have demonstrated that bacteriophages can be effective for treating bacterial infections that are resistant to multiple drugs. The capability of certain bacteriophages to reverse antibiotic resistance, as well as resistance to human complement and other bacteriophages seems to be a significant benefit of bacteriophage therapy, despite the predictable appearance of bacteriophage-resistant strains. Bacteriophages or specific products derived from them can improve antimicrobial effectiveness by decreasing bacteria's harmful properties through changes to fundamental bacterial structures, mainly their cell walls and membranes. Despite several ongoing issues regarding their practical use, it seems that bacteriophage-based treatments combined with antibiotics can serve as an effective solution to addressing the spread of antimicrobial resistance.

抗菌素耐药性持续增加对全球公共卫生构成重大威胁。应用不干扰人体自然菌群的杀菌噬菌体成为一种有前途的替代治疗方法。本节提供了在实验室和人体试验中使用噬菌体疗法治疗特定细菌感染的深入检查。增加使用噬菌体作为对抗生素耐药的细菌感染的补充或替代治疗的好处和障碍进行了审查。使用适应性强的噬菌体群体，结合抗生素化合物，作为分子工具来对抗宿主环境中快速进化的致病菌，呈现出显著的病毒学复杂性。临床前研究、孤立的临床报告和一些随机临床试验表明，噬菌体可有效治疗对多种药物具有耐药性的细菌感染。某些噬菌体逆转抗生素耐药性的能力，以及对人类补体和其他噬菌体的耐药性，似乎是噬菌体治疗的一个重要益处，尽管可以预测噬菌体耐药菌株的出现。噬菌体或由其衍生的特定产物可以通过改变细菌的基本结构（主要是细胞壁和细胞膜）来减少细菌的有害特性，从而提高抗菌效果。尽管在实际应用中存在一些问题，但基于噬菌体的治疗与抗生素相结合似乎可以作为解决抗菌素耐药性传播的有效解决方案。

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引用次数: 0

Pathogenic diversity of Cryptococcus in Galleria mellonella extends beyond classical virulence factors mellonella隐球菌的致病多样性超出了经典的毒力因素

IF 6.2 Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.tcsw.2025.100153

Bianca A.G. Sena , Marlon D.M. Santos , Cassia M. Souza , Amanda C. Camillo-Andrade , Haroldo C. de Oliveira , Flavia C.G. Dos Reis , Rafael F. Castelli , Diogo Kuczera , Henrique R.M. Antoniolli , Hellen G.G. Santos , Charley C. Staats , Guilherme L. Sassaki , Paulo C. Carvalho , Marcio L. Rodrigues

Pathogenic determinants in the Cryptococcus genus have been extensively studied, often using standard laboratory isolates. Here, we analyzed the virulence of ten Cryptococcus isolates from diverse sources, species, and genotypes. These isolates exhibited marked differences in their ability to colonize and kill the invertebrate host Galleria mellonella, as well as in their interactions with hemocytes. Capsule formation also varied widely among isolates, with no clear correlation between virulence in G. mellonella and source of isolation, species, fungal burden, capsule size, or interaction with larval hemocytes. To further investigate the basis of this pathogenic diversity, we selected two hypervirulent isolates (C. deuterogattii and C. neoformans) and two hypovirulent isolates (C. gattii and C. neoformans) for in-depth analysis. Differences in the induction of antimicrobial peptides during infection did not account for the observed variation in virulence. Genomic analysis of capsule-related genes, scanning electron microscopy of capsule morphology in vitro and in vivo, and nuclear magnetic resonance of the major capsular polysaccharide all revealed high variability among isolates, but none of these features correlated with virulence. Proteomic profiling of cellular extracts showed that virulent strains were enriched in proteins associated with oxidative processes. Supplementation with an antioxidant during infection increased the virulence of hypovirulent isolates in G. mellonella. These results reveal a high pathogenic diversity in Cryptococcus that goes beyond its classical virulence factors.

隐球菌属的致病决定因素已被广泛研究，通常使用标准的实验室分离物。在这里，我们分析了来自不同来源、种类和基因型的10株隐球菌的毒力。这些分离株在定植和杀死无脊椎宿主mellonella Galleria的能力以及与血细胞的相互作用方面表现出明显的差异。不同菌株的荚膜形成也有很大的差异，在大黄蜂的毒力与分离来源、种类、真菌负荷、荚膜大小或与幼虫血细胞的相互作用之间没有明确的相关性。为了进一步研究这种致病多样性的基础，我们选择了两个高毒分离株（C. deuterogattii和C. neoformans）和两个低毒分离株（C. gatii和C. neoformans）进行深入分析。感染期间抗菌肽诱导的差异并不能解释观察到的毒力变化。荚膜相关基因的基因组分析、体外和体内荚膜形态的扫描电镜以及主要荚膜多糖的核磁共振都显示出菌株之间的高度变异，但这些特征都与毒力无关。细胞提取物的蛋白质组学分析表明，毒性菌株富含与氧化过程相关的蛋白质。在感染期间补充抗氧化剂增加了低毒力菌株的毒力。这些结果揭示了隐球菌的高致病性多样性，超出了其经典的毒力因素。

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引用次数: 0