共查询到20条相似文献，搜索用时 15 毫秒
1.
Isabella A. Joubert Michael Otto Tobias Strunk Andrew J. Currie 《International journal of molecular sciences》2022,23(2)
Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis, a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality. 相似文献
2.
Maria Beatriz Takahashi Aline Florencio Teixeira Ana Lucia Tabet Oller Nascimento 《International journal of molecular sciences》2022,23(24)
Leptospirosis is a neglected infectious disease with global impact on both humans and animals. The increase in urban development without sanitation planning is one of the main reasons for the disease spreading. The symptoms are similar to those of flu-like diseases, such as dengue, yellow fever, and malaria, which can result in a misleading clinical diagnosis. The characterization of host–pathogen interactions is important in the development of new vaccines, treatments, and diagnostics. However, the pathogenesis of leptospirosis is not well understood, and many gaps remain to be addressed. Here, we aimed to determine if Leptospira strains, virulent, culture-attenuated, and saprophytic, and the major outer membrane proteins OmpL37, OmpL1, LipL21, LipL41, and LipL46 are able to adhere to different endothelial, epithelial and fibroblast cell lines in vitro. We showed that virulent leptospires robustly bind to all cells compared to the culture-attenuated and saprophytic lines. The recombinant proteins exhibited certain adhesion, but only OmpL1 and LipL41 were able to bind to several cell lines, either in monolayer or in cell suspension. Blocking OmpL1 with polyclonal antibodies caused a decrease in bacterial binding to cells, contrasting with an increase observed when anti-LipL41 antibodies were used. The adhesion of OmpL1 to HMEC-1 and EA.hy926 was inhibited when cells were pre-incubated with collagen IV, suggesting that both compete for the same cell receptor. We present here for the first time the interaction of five leptospiral outer membrane proteins with several cell lines, and we conclude that LipL41 and OmpL1 may have an impact on leptospiral adhesion to mammalian cells and may mediate the colonization process in leptospiral pathogenesis. 相似文献
3.
Chuan-Jie Zhang Shi-Xing Wang Yan-Na Liang Sheng-Hui Wen Bao-Zhu Dong Zheng Ding Li-Yun Guo Xiao-Qiong Zhu 《International journal of molecular sciences》2021,22(2)
Fungal effectors play important roles in host–pathogen interactions. Botryosphaeria dothidea is an ascomycetous fungus that is responsible for the diseases of hundreds of woody plant species, including apple ring rot, which seriously affects apples worldwide. However, little is known about the effectors of B. dothidea. In this study, we analyzed the B. dothidea genome and predicted 320 candidate effector genes, 124 of which were successfully amplified and cloned. We investigated the effects of these genes on plant cell death in Nicotiana benthamiana while using a transient expression system. Twenty-four hours after initial inoculation with Agrobacterium tumefaciens cells carrying candidate effectors, the infiltrated leaves were challenged with A. tumefaciens cells carrying the BAX gene. In total, 116 candidate effectors completely inhibited, while one partially inhibited, the programmed cell death (PCD) of N. benthamiana induced by BAX, whereas seven candidate effectors had no effect. We then further tested seven candidate effectors able to suppress BAX-triggered PCD (BT-PCD) and found that they all completely inhibited PCD triggered by the elicitors INF1, MKK1, and NPK1. This result suggests that these effectors were activated in order to suppress pathogen-associated molecular pattern-triggered immunity. The signal peptides of these candidate effectors exhibited secretory activity in yeast (pSUC2 vector). Moreover, the respective deletion of Bdo_11198 and Bdo_12090 significantly reduced the virulence of B. dothidea. These results suggest that these effectors play important roles in the interaction of B. dothidea with its hosts. 相似文献
4.
Jian Luo Jinzhi Xu Chaolu Xie Zuoming Zhao Junrui Guo Yuan Wen Tian Li Zeyang Zhou 《International journal of molecular sciences》2022,23(14)
Microsporidia are obligate intracellular parasites that infect a wide variety of hosts ranging from invertebrates to vertebrates. These parasites have evolved strategies to directly hijack host mitochondria for manipulating host metabolism and immunity. However, the mechanism of microsporidia interacting with host mitochondria is unclear. In the present study, we show that microsporidian Encephalitozoon greatly induce host mitochondrial fragmentation (HMF) in multiple cells. We then reveal that the parasites promote the phosphorylation of dynamin 1-like protein (DRP1) at the 616th serine (Ser616), and dephosphorylation of the 637th serine (Ser637) by highly activating mitochondrial phosphoglycerate mutase 5 (PGAM5). These phosphorylation modifications result in the translocation of DRP1 from cytosol to the mitochondrial outer membrane, and finally lead to HMF. Furthermore, treatment with mitochondrial division inhibitor 1 (Mdivi1) significantly reduced microsporidian proliferation, indicating that the HMF are crucial for microsporidian replication. In summary, our findings reveal the mechanism that microsporidia manipulate HMF and provide references for further understanding the interactions between these ubiquitous pathogens with host mitochondria. 相似文献
5.
Daniel H. Stones Anne-Marie Krachler 《International journal of molecular sciences》2015,16(2):2626-2640
The ability of bacterial species to colonize and infect host organisms is critically dependent upon their capacity to adhere to cellular surfaces of the host. Adherence to cell surfaces is known to be essential for the activation and delivery of certain virulence factors, but can also directly affect host cell signaling to aid bacterial spread and survival. In this review we will discuss the recent advances in the field of bacterial adhesion, how we are beginning to unravel the effects adhesins have on host cell signaling, and how these changes aid the bacteria in terms of their survival and evasion of immune responses. Finally, we will highlight how the exploitation of bacterial adhesins may provide new therapeutic avenues for the treatment of a wide range of bacterial infections. 相似文献
6.
Luis A. Arteaga-Blanco Dumith Chequer Bou-Habib 《International journal of molecular sciences》2021,22(19)
The nano-sized membrane enclosed extracellular vesicles (EVs) released by virtually all cell types play an essential role in intercellular communication via delivering bio-molecules, such as nucleic acids, proteins, lipids, and other molecules to recipient cells. By mediating an active and steady-state cell-to-cell communication, EVs contribute to regulating and preserving cellular homeostasis. On the other hand, EVs can also spread pathogen-derived molecules during infections, subverting the host immune responses during infections and thus worsening pathophysiological processes. In recent years, the biological functioning of EVs has become a widespread research field in basic and clinical branches of medical sciences due to their potential role in therapeutic applications for several diseases. This review aims to summarize the main recent findings regarding the implication of EVs shed by human macrophages (MΦ-EVs) and how they can modulate the host immune response to control or increase the damage caused by infectious agents. We will also present the methods used to describe MΦ-EVs, as well as the potential of these EVs as disease diagnostic tools for some human pathogens. We believe that an in-depth understanding of the host–pathogen interactions mediated by MΦ-EVs may trigger the development of innovative therapeutic strategies against infectious diseases. 相似文献
7.
Asahiro Morishita Kyoko Oura Tomoko Tadokoro Koji Fujita Joji Tani Tsutomu Masaki 《International journal of molecular sciences》2021,22(7)
The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host–pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens. 相似文献
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Kaluhannadige R. E. Padmathilake Wannakuwattewaduge Gerard Dilantha Fernando 《International journal of molecular sciences》2022,23(7)
Leptosphaeria maculans causes blackleg disease, which is one of the most destructive diseases of canola (Brassica napus L.). Due to the erosion of the current resistance in B. napus, it is pivotal to introduce new resistant genotypes to the growers. This study evaluated the potential of Rlm7 gene as resistance to its corresponding avirulence AvrLm7 gene is abundant. The Rlm7 line was inoculated with L. maculans isolate with AvrLm7; UMAvr7; and the CRISPR/Cas9 knockout AvrLm7 mutant, umavr7, of the same isolate to cause incompatible and compatible interactions, respectively. Dual RNA-seq showed differential gene expressions in both interactions. High expressions of virulence-related pathogen genes-CAZymes, merops, and effector proteins after 7-dpi in compatible interactions but not in incompatible interaction—confirmed that the pathogen was actively virulent only in compatible interactions. Salicyclic and jasmonic acid biosynthesis and signaling-related genes, defense-related PR1 gene (GSBRNA2T00150001001), and GSBRNA2T00068522001 in the NLR gene family were upregulated starting as early as 1- and 3-dpi in the incompatible interaction and the high upregulation of those genes after 7-dpi in compatible interactions confirmed the early recognition of the pathogen by the host and control it by early activation of host defense mechanisms in the incompatible interaction. 相似文献
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Svetlana Kononova Ekaterina Litvinova Timur Vakhitov Maria Skalinskaya Stanislav Sitkin 《International journal of molecular sciences》2021,22(8)
The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed. 相似文献
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Alfalfa has emerged as one of the most important forage crops, owing to its wide adaptation and high biomass production worldwide. In the last decade, the emergence of bacterial stem blight (caused by Pseudomonas syringae pv. syringae ALF3) in alfalfa has caused around 50% yield losses in the United States. Studies are being conducted to decipher the roles of the key genes and pathways regulating the disease, but due to the sparse knowledge about the infection mechanisms of Pseudomonas, the development of resistant cultivars is hampered. The database alfaNET is an attempt to assist researchers by providing comprehensive Pseudomonas proteome annotations, as well as a host–pathogen interactome tool, which predicts the interactions between host and pathogen based on orthology. alfaNET is a user-friendly and efficient tool and includes other features such as subcellular localization annotations of pathogen proteins, gene ontology (GO) annotations, network visualization, and effector protein prediction. Users can also browse and search the database using particular keywords or proteins with a specific length. Additionally, the BLAST search tool enables the user to perform a homology sequence search against the alfalfa and Pseudomonas proteomes. With the successful implementation of these attributes, alfaNET will be a beneficial resource to the research community engaged in implementing molecular strategies to mitigate the disease. alfaNET is freely available for public use at http://bioinfo.usu.edu/alfanet/. 相似文献
14.
Shengjie Sun Pitambar Poudel Emil Alexov Lin Li 《International journal of molecular sciences》2022,23(18)
This review outlines the role of electrostatics in computational molecular biophysics and its implication in altering wild-type characteristics of biological macromolecules, and thus the contribution of electrostatics to disease mechanisms. The work is not intended to review existing computational approaches or to propose further developments. Instead, it summarizes the outcomes of relevant studies and provides a generalized classification of major mechanisms that involve electrostatic effects in both wild-type and mutant biological macromolecules. It emphasizes the complex role of electrostatics in molecular biophysics, such that the long range of electrostatic interactions causes them to dominate all other forces at distances larger than several Angstroms, while at the same time, the alteration of short-range wild-type electrostatic pairwise interactions can have pronounced effects as well. Because of this dual nature of electrostatic interactions, being dominant at long-range and being very specific at short-range, their implications for wild-type structure and function are quite pronounced. Therefore, any disruption of the complex electrostatic network of interactions may abolish wild-type functionality and could be the dominant factor contributing to pathogenicity. However, we also outline that due to the plasticity of biological macromolecules, the effect of amino acid mutation may be reduced, and thus a charge deletion or insertion may not necessarily be deleterious. 相似文献
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Quanhui Yan Xiaodi Liu Yawei Sun Weijun Zeng Yuwan Li Feifan Zhao Keke Wu Shuangqi Fan Mingqiu Zhao Jinding Chen Lin Yi 《International journal of molecular sciences》2022,23(7)
Swine enteric coronavirus (SeCoV) causes acute gastroenteritis and high mortality in newborn piglets. Since the last century, porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) have swept farms all over the world and caused substantial economic losses. In recent years, porcine delta coronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) have been emerging SeCoVs. Some of them even spread across species, which made the epidemic situation of SeCoV more complex and changeable. Recent studies have begun to reveal the complex SeCoV–host interaction mechanism in detail. This review summarizes the current advances in autophagy, apoptosis, and innate immunity induced by SeCoV infection. These complex interactions may be directly involved in viral replication or the alteration of some signal pathways. 相似文献
17.
Anna Helena Mazurek &#x;ukasz Szeleszczuk Tomasz Gubica 《International journal of molecular sciences》2021,22(17)
Cyclodextrins (CDs) are highly respected for their ability to form inclusion complexes via host–guest noncovalent interactions and, thus, ensofance other molecular properties. Various molecular modeling methods have found their applications in the analysis of those complexes. However, as showed in this review, molecular dynamics (MD) simulations could provide the information unobtainable by any other means. It is therefore not surprising that published works on MD simulations used in this field have rapidly increased since the early 2010s. This review provides an overview of the successful applications of MD simulations in the studies on CD complexes. Information that is crucial for MD simulations, such as application of force fields, the length of the simulation, or solvent treatment method, are thoroughly discussed. Therefore, this work can serve as a guide to properly set up such calculations and analyze their results. 相似文献
18.
Izabela Perkowska Marta Potrykus Joanna Siwinska Dominika Siudem Ewa Lojkowska Anna Ihnatowicz 《International journal of molecular sciences》2021,22(12)
Coumarins belong to a group of secondary metabolites well known for their high biological activities including antibacterial and antifungal properties. Recently, an important role of coumarins in plant resistance to pathogens and their release into the rhizosphere upon pathogen infection was discovered. It is also well documented that coumarins play a crucial role in the Arabidopsis thaliana growth under Fe-limited conditions. However, the mechanisms underlying interplay between plant resistance, accumulation of coumarins and Fe status, remain largely unknown. In this work, we investigated the effect of both mentioned factors on the disease severity using the model system of Arabidopsis/Dickeya spp. molecular interactions. We evaluated the disease symptoms in Arabidopsis plants, wild-type Col-0 and its mutants defective in coumarin accumulation, grown in hydroponic cultures with contrasting Fe regimes and in soil mixes. Under all tested conditions, Arabidopsis plants inoculated with Dickeya solani IFB0099 strain developed more severe disease symptoms compared to lines inoculated with Dickeya dadantii 3937. We also showed that the expression of genes encoding plant stress markers were strongly affected by D. solani IFB0099 infection. Interestingly, the response of plants to D. dadantii 3937 infection was genotype-dependent in Fe-deficient hydroponic solution. 相似文献
19.
Magda Teixeira-Nunes Pascal Retailleau Martine Comisso Vincent Deruelle Undine Mechold Louis Renault 《International journal of molecular sciences》2022,23(12)
Many pathogens manipulate host cell cAMP signaling pathways to promote their survival and proliferation. Bacterial Exoenzyme Y (ExoY) toxins belong to a family of invasive, structurally-related bacterial nucleotidyl cyclases (NC). Inactive in bacteria, they use proteins that are uniquely and abundantly present in eukaryotic cells to become potent, unregulated NC enzymes in host cells. Other well-known members of the family include Bacillus anthracis Edema Factor (EF) and Bordetella pertussis CyaA. Once bound to their eukaryotic protein cofactor, they can catalyze supra-physiological levels of various cyclic nucleotide monophosphates in infected cells. Originally identified in Pseudomonas aeruginosa, ExoY-related NC toxins appear now to be more widely distributed among various γ- and β-proteobacteria. ExoY-like toxins represent atypical, poorly characterized members within the NC toxin family. While the NC catalytic domains of EF and CyaA toxins use both calmodulin as cofactor, their counterparts in ExoY-like members from pathogens of the genus Pseudomonas or Vibrio use actin as a potent cofactor, in either its monomeric or polymerized form. This is an original subversion of actin for cytoskeleton-targeting toxins. Here, we review recent advances on the different members of the NC toxin family to highlight their common and distinct functional characteristics at the molecular, cytotoxic and enzymatic levels, and important aspects that need further characterizations. 相似文献
20.
Mateusz Kurcinski Sebastian Kmiecik Mateusz Zalewski Andrzej Kolinski 《International journal of molecular sciences》2021,22(14)
Most of the protein–protein docking methods treat proteins as almost rigid objects. Only the side-chains flexibility is usually taken into account. The few approaches enabling docking with a flexible backbone typically work in two steps, in which the search for protein–protein orientations and structure flexibility are simulated separately. In this work, we propose a new straightforward approach for docking sampling. It consists of a single simulation step during which a protein undergoes large-scale backbone rearrangements, rotations, and translations. Simultaneously, the other protein exhibits small backbone fluctuations. Such extensive sampling was possible using the CABS coarse-grained protein model and Replica Exchange Monte Carlo dynamics at a reasonable computational cost. In our proof-of-concept simulations of 62 protein–protein complexes, we obtained acceptable quality models for a significant number of cases. 相似文献