Abstract：
:The development of bacterial resistance against current antibiotic drugs necessitates a continuous renewal of the arsenal of efficacious drugs. This imperative has not been met by the output of antibiotic research and development of the past decades for various reasons, including the declining efforts of large pharma companies in this area. Moreover, the majority of novel antibiotics are chemical derivatives of existing structures that represent mostly step innovations, implying that the available chemical space may be exhausted. This review negates this impression by showcasing recent achievements in lead finding and optimization of antibiotics that have novel or unexplored chemical structures. Not surprisingly, many of the novel structural templates like teixobactins, lysocin, griselimycin, or the albicidin/cystobactamid pair were discovered from natural sources. Additional compounds were obtained from the screening of synthetic libraries and chemical synthesis, including the gyrase-inhibiting NTBI's and spiropyrimidinetrione, the tarocin and targocil inhibitors of wall teichoic acid synthesis, or the boronates and diazabicyclo[3.2.1]octane as novel β-lactamase inhibitors. A motif that is common to most clinically validated antibiotics is that they address hotspots in complex biosynthetic machineries, whose functioning is essential for the bacterial cell. Therefore, an introduction to the biological targets-cell wall synthesis, topoisomerases, the DNA sliding clamp, and membrane-bound electron transport-is given for each of the leads presented here.
journal_name
Curr Top Microbiol Immunoljournal_title
Current topics in microbiology and immunologyauthors
Klahn P,Brönstrup Mdoi
10.1007/82_2016_501subject
Has Abstractpub_date
2016-01-01 00:00:00pages
365-417eissn
0070-217Xissn
2196-9965journal_volume
398pub_type
杂志文章,评审abstract：:Picornavirus 5' NCRs contain IRES elements that have been divided into two groups, exemplified by PV (type 1) and EMCV (type 2). These elements are functionally related and have an intriguing level of structural and sequence similarity. Some conserved RNA sequences and/or structures may correspond to cis-acting elemen...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-642-79663-0_2
更新日期：1995-01-01 00:00:00
abstract：:Understanding how cell growth is regulated in response to environmental signals remains a challenging biological problem. Recent studies indicate the TOR (target of rapamycin) kinase acts within an intracellular regulatory network used by eukaryotic cells to regulate their growth according to nutrient availability. Th...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-642-18930-2_3
更新日期：2004-01-01 00:00:00
abstract：:The family of protein tyrosine phosphatases (PTPs) includes 107 genes in humans that are diverse in their structures and expression profiles. The majority are present in immune cells and play various roles in either inhibiting or promoting the duration and amplitude of signaling cascades. Several PTPs, including TC-PT...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2017_68
更新日期：2017-01-01 00:00:00
abstract：:DNA replication is an important step in the life cycle of every cell that ensures the continuous flow of genetic information from one generation to the next. In all organisms, chromosome replication must be coordinated with overall cell growth. Helicobacter pylori growth strongly depends on its interaction with the ho...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-50520-6_4
更新日期：2017-01-01 00:00:00
abstract：:Rho GTPases are molecular switches controlling a broad range of cellular processes including lymphocyte activation. Not surprisingly, Rho GTPases are now recognized as pivotal regulators of antigen-specific T cell activation by APCs and immunological synapse formation. This review summarizes recent advances in our und...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/3-540-27511-8_5
更新日期：2005-01-01 00:00:00
abstract：:Host cell attachment by influenza A viruses is mediated by the hemagglutinin glycoprotein (HA), and the recognition of specific types of sialic acid -containing glycan receptors constitutes one of the major determinants of viral host range and transmission properties. Structural studies have elucidated some of the vir...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2014_423
更新日期：2014-01-01 00:00:00
abstract：:The field of autophagy research has advanced rapidly in recent years, with important discoveries made in relation to both molecular mechanisms and physiological functions. Initially, autophagy was thought to be primarily a response to starvation. Although this might be true in lower eukaryotes, this catabolic process ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-642-00302-8_3
更新日期：2009-01-01 00:00:00
abstract：:The innate host response to influenza virus infection plays a critical role in determining the subsequent course of infection and the clinical outcome of disease. The host has a diverse array of detection and effector mechanisms that are able to recognize and initiate effective antiviral responses. In opposition, the ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2014_412
更新日期：2015-01-01 00:00:00
abstract：:Enzootic nasal adenocarcinoma is a contagious tumour of the mucosal nasal glands affecting young adult sheep or goats. The disease occurs naturally in all continents except Australia and New Zealand. Clinical signs include continuous nasal discharge, respiratory distress, exophthalmos and skull deformations. The tumou...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-642-55638-8_8
更新日期：2003-01-01 00:00:00
abstract：:Imprinting is the uniparental expression of a set of genes. Somatic cells carry two haploid sets of chromosomes, one maternal and one paternal, while germ cells contain only one of the two forms of chromosomes, male or female. This implies that during early embryogenesis the cells committed for developing the future g...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/3-540-31390-7_8
更新日期：2006-01-01 00:00:00
abstract：:Swine influenza is a continual problem for the Swine industry and can pose a public health threat as evidenced by the 2009 H1N1 influenza virus pandemic. Given its importance, it is not surprising to find papers describing the disease from the early 20th century. In this chapter, we discuss the history of Swine influe...
journal_title：Current topics in microbiology and immunology
pub_type： 历史文章,杂志文章,评审
doi：10.1007/82_2011_197
更新日期：2013-01-01 00:00:00
abstract：:Hemopoietic cells express relatively high levels of the type I phosphoinositide (PI) 3-kinase isoforms, with p110δ and γ exhibiting specialized signaling functions in neutrophils, monocytes, mast cells, and lymphocytes. In platelets, p110β appears to be the dominant PI 3-kinase isoform regulating platelet activation, ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2010_61
更新日期：2010-01-01 00:00:00
abstract：:There is a trend toward viral-based hybrid systems to furnish viral nanoparticles with enhanced features, for function beyond a delivery vehicle. Such hybrids have included Nanogold for microwave release, quantum dots and fluorescent moieties, to provide simultaneous imaging capabilities, and iron oxide particles for ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-540-69379-6_3
更新日期：2009-01-01 00:00:00
abstract：:Atrophic rhinitis is a widespread and economically important swine disease caused by Pasteurella multocida and Bordetella bronchiseptica. The disease is characterized by atrophy of the nasal turbinate bones, which results in a shortened and deformed snout in severe cases. P. multocida toxin and B. bronchiseptica dermo...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2012_206
更新日期：2012-01-01 00:00:00
abstract：:The application of fundamental concepts about the packaging of the adenovirus genome has contributed significantly to the development of therapeutic viral vectors for gene therapy. The packaging of adenovirus DNA into virus particles requires a cis-acting domain at the left end of the genome. This region contains a se...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-662-05597-7_6
更新日期：2003-01-01 00:00:00
abstract：:By now, it is well established that the error rate of the RNA-dependent RNA polymerase (RdRp) that replicates RNA virus genomes is a primary driver of the mutation frequencies observed in RNA virus populations-the basis for the RNA quasispecies. Over the last 10 years, a considerable amount of work has uncovered the m...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2015_483
更新日期：2016-01-01 00:00:00
abstract：:Wild aquatic bird populations have long been considered the natural reservoir for influenza A viruses with virus transmission from these birds seeding other avian and mammalian hosts. While most evidence still supports this dogma, recent studies in bats have suggested other reservoir species may also exist. Extensive ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2014_396
更新日期：2014-01-01 00:00:00
abstract：:Our understanding of the mechanisms involved in the formation of the complex arrangement of neurons and their interconnections within the brain has made significant progress in recent years. Current research has uncovered a network of intracellular signaling events that provide precise coordination of a diverse array ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2010_82
更新日期：2010-01-01 00:00:00
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journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2017_18
更新日期：2017-01-01 00:00:00
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journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章
doi：10.1007/978-3-642-85226-8_31
更新日期：1996-01-01 00:00:00
abstract：:Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of ...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章
doi：10.1007/978-3-642-38919-1_19
更新日期：2013-01-01 00:00:00
abstract：:The increased risk for severe dengue disease during secondary dengue virus (DENV) infections, along with the clinical and pathological evidence pointing to cytokines as the proximal mediators of disease, has interested cellular immunologists in exploring the role of DENV-specific T lymphocytes in the pathogenesis of d...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-642-02215-9_7
更新日期：2010-01-01 00:00:00
abstract：:Animal models of ricin toxicosis are necessary for testing the efficacy of therapeutic measures, as well studying the mechanisms by which ricin exerts its toxicity in intact animals. Because ricin can serve as a particularly well-characterized model of tissue damage, and the host response to that damage, studies of th...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章
doi：10.1007/82_2011_173
更新日期：2012-01-01 00:00:00
abstract：:Hendra virus, a novel and fatally zoonotic member of the family Paramyxoviridae, was first described in Australia in 1994. Periodic spillover from its natural host (fruit bats) results in catastrophic disease in horses and occasionally the subsequent infection of humans. Prior to 2011, 14 equine incidents involving se...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2012_214
更新日期：2012-01-01 00:00:00
abstract：:Every enveloped virus fuses its membrane with a host cell membrane, thereby releasing its genome into the cytoplasm and initiating the viral replication cycle. In each case, one or a small set of viral surface transmembrane glycoproteins mediates fusion. Viral fusion proteins vary in their mode of activation and in st...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/3-540-26764-6_2
更新日期：2005-01-01 00:00:00
abstract：:The use of appropriate fluorescent proteins has allowed the use of FRET microscopy for investigation of intermolecular interactions in living cells. This method has the advantage of both being dynamic and of working at the subcellular level, so that the time and place where proteins interact can be visualized. We have...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-540-93864-4_2
更新日期：2009-01-01 00:00:00
abstract：:Tumor DNA contains valuable clues about the origin and pathogenesis of human cancers. Alterations in DNA methylation can lead to silencing of genes associated with distinct tumorigenic pathways. These pathway-specific DNA methylation changes help define tumor-specific DNA methylation profiles that can be used to furth...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/3-540-31181-5_8
更新日期：2006-01-01 00:00:00
abstract：:The mitogenic dermonecrotic toxin from Pasteurella multocida (PMT) is a 1285-residue multipartite protein that belongs to the A-B family of bacterial protein toxins. Through its G-protein-deamidating activity on the α subunits of heterotrimeric G(q)-, G(i)- and G(12/13)-proteins, PMT potently stimulates downstream mit...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/82_2012_219
更新日期：2012-01-01 00:00:00
abstract：:Epstein-Barr nuclear antigen 1 (EBNA1) plays multiple important roles in EBV latent infection and has also been shown to impact EBV lytic infection. EBNA1 is required for the stable persistence of the EBV genomes in latent infection and activates the expression of other EBV latency genes through interactions with spec...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-22834-1_1
更新日期：2015-01-01 00:00:00
abstract：:Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of...
journal_title：Current topics in microbiology and immunology
pub_type： 杂志文章,评审
doi：
更新日期：1995-01-01 00:00:00
