LC3相关吞噬作用与病原微生物感染

LC3相关吞噬作用(LC3-associated phagocytosis,LAP)是一种宿主细胞吞噬和降解病原体的高效过程。近年来越来越多的研究表明,LAP在清除病原微生物感染过程中具有非常重要的作用,其作用机制不同于传统的吞噬作用和自噬作用。在外源刺激下,宿主细胞通过招募自噬相关的蛋白实现LC3向单层膜吞噬泡的聚集,从而提高其吞噬和杀伤病原体的效率。不同病原微生物应对LAP的杀伤作用的方式是不同的,本文对LAP发生的一般规律、各种微生物感染过程中LAP发生的不同情况及其近期研究进展予以综述。     

Quorum-quenching microbial infections: mechanisms and implications

The discovery of antibiotics early in the past century marked the beginning of active control and prevention of infectious microbial diseases. However, extensive use of antibiotics has also unavoidably resulted in the emergence of ‘superbugs’ that resist conventional antibiotics. The finding that many pathogens rely on cell-to-cell communication mechanisms, known as quorum sensing, to synchronize microbial activities essential for infection and survival in the host suggests a promising disease control strategy, i.e. quenching microbial quorum sensing or in short, quorum quenching. Work over the past few years has demonstrated that quorum-quenching mechanisms are widely conserved in many prokaryotic and eukaryotic organisms. These naturally occurring quorum-quenching mechanisms appear to play important roles in microbe–microbe and pathogen–host interactions and have been used, or served as lead compounds, in developing and formulating a new generation of antimicrobials. Characterization of the crystal structures of several types of quorum-quenching enzymes has provided valuable information to elucidate the catalytic mechanisms, as well as clues for future protein tailoring and molecular improvement. The discovery of quorum-sensing signal degradation enzymes in mammalian species represents a new milestone in quorum sensing and quorum quenching research. The finding highlights the importance of investigating their roles in host innate defence against infectious diseases and to determine the factors influencing their in vivo concentrations and catalytic activities.     

Diagnostic microbial microarrays in soil ecology

Soil microbial communities are responsible for important physiological and metabolic processes. In the last decade soil microorganisms have been frequently analysed by cultivation-independent techniques because only a minority of the natural microbial communities are accessible by cultivation. Cultivation-independent community analyses have revolutionized our understanding of soil microbial diversity and population dynamics. Nevertheless, many methods are still laborious and time-consuming, and high-throughput methods have to be applied in order to understand population shifts at a finer level and to be better able to link microbial diversity with ecosystems functioning. Microbial diagnostic microarrays (MDMs) represent a powerful tool for the parallel, high-throughput identification of many microorganisms. Three categories of MDMs have been defined based on the nature of the probe and target molecules used: phylogenetic oligonucleotide microarrays with short oligonucleotides against a phylogenetic marker gene; functional gene arrays containing probes targeting genes encoding specific functions; and community genome arrays employing whole genomes as probes. In this review, important methodological developments relevant to the application of the different types of diagnostic microarrays in soil ecology will be addressed and new approaches, needs and future directions will be identified, which might lead to a better insight into the functional activities of soil microbial communities.     

Diagnostic tests for primary renal hypouricemia

Primary renal hypouricemia is a genetic disorder characterized by defective renal uric acid (UA) reabsorption with complications such as nephrolithiasis and exercise-induced acute renal failure. The known causes are: defects in the SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and also impairment of voltage urate transporter (URATv1), encoded by SLC2A9 (GLUT9) gene. Diagnosis is based on hypouricemia (<119 μmol/L) and increased fractional excretion of UA (>10%). To date, the cases with mutations in hURAT1 gene have been reported in East Asia only. More than 100 Japanese patients have been described. Hypouricemia is sometimes overlooked; therefore, we have set up the flowchart for this disorder. The patients were selected for molecular analysis from 620 Czech hypouricemic patients. Secondary causes of hyperuricosuric hypouricemia were excluded. The estimations of (1) serum UA, (2) excretion fraction of UA, and (3) analysis of hURAT1 and URATv1 genes follow. Three transitions and one deletion (four times) in SLC22A12 gene and one nucleotide insertion in SLC2A9 gene in seven Czech patients were found. Three patients had acute renal failure and urate nephrolithiasis. In addition, five nonsynonymous sequence variants and three nonsynonymous sequence variants in SLC2A9 gene were found in two UK patients suffering from acute renal failure. Our finding of the defects in SLC22A12 and SLC2A9 genes gives further evidence of the causative genes of primary renal hypouricemia and supports their important role in regulation of serum urate levels in humans.     

Macrophage cell death in microbial infections

Macrophages can respond to microbial infections with programmed cell death. The major cell death pathways of apoptosis, pyroptosis and necroptosis are tightly regulated to ensure adequate immune reactions to virulent and persistent invaders. Macrophage death eliminates the replicative niche of intracellular pathogens and induces immune attack. Not surprisingly, successful pathogens have evolved strategies to modulate macrophage cell death pathways to enable microbial survival and replication. Uncontrolled macrophage death can also lead to tissue damage, which may augment bacterial dissemination and pathology. In this review, we highlight how pathogens hijack macrophage cell death signals to promote microbial survival and immune evasion.     

Molecular analysis of ancient microbial infections

The detection of ancient microbial DNA offers a new approach for the study of infectious diseases, their occurrence, frequency and host-pathogen interaction in historic times and populations. Moreover, data obtained from skeletal and mummified tissue may represent an important completion of contemporary phylogenetic analyses of pathogens. In the last few years, a variety of bacterial, protozoal and viral infections have been detected in ancient tissue samples by amplification and characterization of specific DNA fragments. This holds particularly true for the identification of the Mycobacterium tuberculosis complex, which seems to be more robust than other microbes due to its waxy, hydrophobic and lipid-rich cell wall. These observations provided useful information about the occurrence, but also the frequency of tuberculosis in former populations. Moreover, these studies suggest new evolutionary models and indicate the route of transmission between human and animals. Until now, other pathogens, such as Mycobacterium leprae, Yersinia pestis, Plasmodium falciparum and others, have occasionally been identified - mostly in single case studies or small sample sizes - as well, although much less information is available on these pathogens in ancient settings. The main reason therefore seems to be the degradation and modification of ancient DNA by progressive oxidative damage. Furthermore, the constant risk of contamination by recent DNA forces to take time and cost effective measures and renders the analysis of ancient microbes difficult. Nevertheless, the study of microbial ancient DNA significantly contributes to the understanding of transmission and spread of infectious diseases, and potentially to the evolution and phylogenetic pathways of pathogens.     

Diagnostic imaging of cancer

Rapid development of imaging techniques provided much more precise methodology of diagnosis, staging and dynamics of cancer. Nowadays the onco-radiodiagnostic units are able to select the optimal imaging technique based on established international protocols. These protocols provide the basis of cancer diagnosis, therapy control and clinical research. The onco-radiodiagnostic unit is essential part of the oncoteam managing the cancer patients. Follow-up protocols are now equally important compared to those of the diagnosis and staging, requiring a continuous interaction between radiologists and physicians. The comprehensive cancer centers with all the necessary imaging techniques are the optimal organizations where professional and economic priorities both can be considered for the benefit of cancer patients.     

Infectomics: genomics and proteomics of microbial infections

The completion of genomic sequences is the greatest triumph of molecular reductionism since the discovery of the DNA double helix in 1953. However, the utility of reductionism is becoming limited and holistic approaches, including theories and techniques, are desperately needed in the postgenomic era. In the field of infectious diseases there is an urgent need for global approaches that can efficiently, precisely and integratively study structural and functional genomics and proteomics of microbial infections (infectomics). The combination of new (e.g. DNA and protein microarrays) and traditional approaches (e.g. cloning, PCR, gene knockout and knockin, and antisense) will help overcome the challenges we are facing today. We assume that the global phenotypic changes (infectomes) in microbes and their host during infections are encoded by the genomes of microbial pathogens and their hosts, expressed in certain environmental conditions devoted to specific microbe-host interactions. Global drug responses (pharmacomes) in microbes and their host can be detected by genomic and proteomic approaches. Genome-wide approaches to genotyping and phenotyping or expression profiling will eventually lead to global dissection of microbial pathogenesis, efficient and rapid diagnosis of infectious diseases, and the development of novel strategies to control infections. The key fundamental issue of infectious diseases is how to globally and integratively understand the interactions between microbial pathogens and their hosts by using infectomics. In this review, we focus on the events that are considered important in infectomics. Electronic Publication     

Diagnostic imaging in lung cancer

Lung cancer is one of the major causes of death as one of the most frequent malignant diseases in Hungary. Imaging examinations, especially computed tomography (CT), magnetic resonance imaging (MRI) and positron emission computed tomography (PET-CT) play eminent role in the detection, differential diagnosis, staging and follow-up of the disease. The purpose of this article is to review the role and efficacy of the available modalities and to define the diagnostic algorithm appropriate in different periods of the disease.     

Physico-chemical properties of microbial antigens and the immuno-allergic tests]

Experiments were conducted on guinea pigs sensitized by the delayed and immediate types of allergy. Different antigens obtained from the strain of Brucella abortus BA-19 were used for sensitization and the resolving action. Comparison of the resolving properties of the corpuscular, soluble (ultrasound treated) antigens and purified protein fractions, polysaccharide and RNA was carried out in the skin reactions of the immediate and delayed type, passive skin anaphylaxis, acute anaphylactic shock, and the Schults-Dale test. Immediate reactions to the purified protein fraction were weaker than those to the whole soluble antigen, by which the animals were sensitized. Polysaccharide and the RNA-fractions proved to be inactive in the allergic reactions.     

Influence of fungal plasmocoagulase on some microbial infections

The comparative investigation of plasmocoagulase and polysaccharide ofCandida albicans and staphylococcal coagulase shows that all substances inhibit the phagocytosis in vitro. These preparations suppress both the seizure of microbial cells by leucocytes and the digestion of phagocytosed microbes. In the experiments in vivo the substances partly inhibit phagocytosis when injected simultaneously with bacteria. When injected in advance, the preparations activated the phagocytosis.Plasmocoagulase and polysaccharide ofC. albicans when injected simultaneously with microbes complicate the infection independently of the etiologic agent.Investigation of plasmocoagulases and polysaccharides isolated from 25 species of fungi shows that most part of them complicates the infection under the simultaneous injection with bacteria. Preliminary injection revealed only extremely weak preventive action of some of them.The biologic activity of the plasmocoagulases and polysaccharides can be compared with that of microbial endotoxines.

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Zusammenfassung Die vergleichende Untersuchung von Plasmacoagulase und Polysaccharide vonCandida albicans und von staphylogener Coagulase zeigt, daß alle Substanzen die Phagozytose in vitro verhindern. Diese Substanzen unterdrücken sowohl das Einfangen der Bakterien durch die Leukozyten als auch die Verdauung der phagozitierten Bakterien. In den Experimenten in vivo unterdrücken die Substanzen teilweise die Phagozytose, wenn sie gleichzeitig mit den Bakterien injiziert werden. Wenn sie aber vorher injiziert werden, aktivieren die Preparate die Phagozytose. Wenn Plasmocoagulase und Polysaccharide vonC. albicans gleichzeitig mit den Bakterien injiziert werden, komplizieren sie die Infektion, unabhängig vom bakteriologischen Erreger. Untersuchungen von Plasmocoagulasen und Polysacchariden, gewonnen von 25 Arten von Fungi, zeigen, daß sie die Infektion meisten Teils komplizieren unter gleichzeitiger Injektion von Bakterien. Vorherige Injektion zeigte nur eine sehr schwache schützende Wirkung von einigen von ihnen. Die biologische Wirkung von Plasmacoagulasen und Polysacchariden kann mit der Wirkung der bakteriellen Endotoxinen verglichen werden.