Abstract：
:The convergence of competitive fitness experiments and phenotypic screening would seem to be an auspicious beginning for validation of an antibacterial target. IMPDH was already identified an essential protein in Mycobacterium tuberculosis when not one, but two, groups discovered inhibitors with promising antitubercular activity. A new target appeared to be born. Surprisingly, the two groups came to completely different conclusions about the vulnerability of IMPDH and its future as a drug target. This viewpoint discusses these papers and how to resolve this conundrum.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
Hedstrom Ldoi
10.1021/acsinfecdis.6b00185subject
Has Abstractpub_date
2017-01-13 00:00:00pages
2-4issue
1issn
2373-8227journal_volume
3pub_type
杂志文章abstract：:The ability to respire and generate adenosine triphosphate (ATP) is essential for the physiology, persistence, and pathogenicity of Mycobacterium tuberculosis, which causes tuberculosis. By employing a lead repurposing strategy, the malarial cytochrome bc1 inhibitor SCR0911 was tested against mycobacteria. Docking stu...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.9b00408
更新日期：2020-04-10 00:00:00
abstract：:The general secretion (Sec) pathway is a conserved essential pathway in bacteria and is the primary route of protein export across the cytoplasmic membrane. During protein export, the signal peptidase LepB catalyzes the cleavage of the signal peptide and subsequent release of mature proteins into the extracellular spa...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.6b00075
更新日期：2016-12-09 00:00:00
abstract：:At present, there is no licensed antiviral drug against dengue virus (DENV) infection. Mouse models of DENV infection have been widely used for preclinical evaluation of antivirals. However, only in a few instances so far have the data obtained from preclinical mouse model testing been associated with data from clinic...
journal_title：ACS infectious diseases
pub_type： 杂志文章,评审
doi：10.1021/acsinfecdis.8b00054
更新日期：2018-07-13 00:00:00
abstract：:Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillb...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.7b00064
更新日期：2017-08-11 00:00:00
abstract：:In order to identify the most attractive starting points for drugs that can be used to prevent malaria, a diverse chemical space comprising tens of thousands to millions of small molecules may need to be examined. Achieving this throughput necessitates the development of efficient ultra-high-throughput screening metho...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.5b00143
更新日期：2016-04-08 00:00:00
abstract：:Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellani...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.9b00263
更新日期：2019-12-13 00:00:00
abstract：:Computer-aided screening of antimicrobial peptides (AMPs) is a promising approach for discovering novel therapies against multidrug-resistant bacterial infections. Here, we functionally and structurally characterized an Escherichia coli-derived AMP (EcDBS1R5) previously designed through pattern identification [α-helic...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.8b00219
更新日期：2018-12-14 00:00:00
abstract：:Recent studies on 3,6-diphenylated imidazopyridazines have demonstrated impressive in vitro activity and in vivo efficacy in mouse models of malaria infection. Herein, we report the synthesis and antiplasmodium evaluation of a new series of amidated analogues and demonstrate that these compounds potently inhibit Plasm...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.0c00481
更新日期：2021-01-08 00:00:00
abstract：:Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintrica...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.6b00098
更新日期：2016-11-11 00:00:00
abstract：:The current explosive epidemic of Zika virus in South and Central America, as well as the Caribbean, poses a global public health emergency. Here we comment on the challenges on development of better diagnosis and potential therapeutics and vaccine for Zika virus. ...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.6b00030
更新日期：2016-03-11 00:00:00
abstract：:Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens. Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.8b00245
更新日期：2019-04-12 00:00:00
abstract：:Enterovirus 71 (EV71) is a major etiological agent of hand, foot, and mouth disease, for which there is no antiviral therapy. We have developed densely sulfated disaccharide heparan sulfate (HS) analogues that are potent small molecule inhibitors of EV71 infection, binding to the viral capsid and acting as decoy recep...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.9b00070
更新日期：2019-10-11 00:00:00
abstract：:Neurotoxicity is an unwanted side effect for patients when receiving parenteral colistin therapy. The development of effective neuroprotective agents that can be coadministered during colistin therapy remains a priority area in antimicrobial chemotherapy. The present study aimed to investigate the protective effect of...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.0c00107
更新日期：2020-06-12 00:00:00
abstract：:Human African trypanosomiasis (HAT) is a fatal infectious disease caused by the eukaryotic pathogen Trypanosoma brucei (Tb). Available treatments are difficult to administer and have significant safety issues. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the parasite polyamine biosynthetic p...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.7b00022
更新日期：2017-07-14 00:00:00
abstract：:MmpL3, an essential mycolate transporter in the inner membrane of Mycobacterium tuberculosis (Mtb), has been identified as a target of multiple, chemically diverse antitubercular drugs. However, several of these molecules seem to have secondary targets and inhibit bacterial growth by more than one mechanism. Here, we ...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.0c00675
更新日期：2021-01-08 00:00:00
abstract：:A method for the fast isolation, propagation, and characterization of very low count bacteriophages active against pathogenic bacterial strains is described in this study. Bacteriophages with a count of 102 phage particles were dynamically adhered from the maximum 10 mL blood plasma sample onto the nanostructured part...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.0c00358
更新日期：2020-10-09 00:00:00
abstract：:Conventional antibiotics are not effective in treating infections caused by drug-resistant or persistent nongrowing bacteria, creating a dire need for the development of new antibiotics. We report that the small molecule nTZDpa, previously characterized as a nonthiazolidinedione peroxisome proliferator-activated recep...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.8b00161
更新日期：2018-11-09 00:00:00
abstract：:To explore the possibility of constrained peptides to target Plasmodium-infected cells, we designed a J domain mimetic derived from Plasmodium falciparum calcium-dependent protein kinase 1 ( PfCDPK1) as a strategy to disrupt J domain binding and inhibit PfCDPK1 activity. The J domain disruptor (JDD) peptide was confor...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.8b00347
更新日期：2019-04-12 00:00:00
abstract：:The spread of plasmid borne resistance enzymes in clinical Staphylococcus aureus isolates is rendering trimethoprim and iclaprim, both inhibitors of dihydrofolate reductase (DHFR), ineffective. Continued exploitation of these targets will require compounds that can broadly inhibit these resistance-conferring isoforms....
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.9b00222
更新日期：2019-11-08 00:00:00
abstract：:The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-...
journal_title：ACS infectious diseases
pub_type： 杂志文章,评审
doi：10.1021/acsinfecdis.0c00052
更新日期：2020-05-08 00:00:00
abstract：:Bacterial coinfection in COVID-19 patients has the potential to complicate treatments and accelerate the development of antibiotic resistance in the clinic due to the widespread use of broad-spectrum antibiotics, including in Indonesia. The surge of COVID-19 patients may worsen antibiotic overuse; therefore, informati...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.1c00006
更新日期：2021-01-27 00:00:00
abstract：:Ebola virus (EBOV), a member of the family Filoviridae, is a nonsegmented negative-sense RNA virus that causes severe, often lethal, disease in humans. EBOV RNA synthesis is carried out by a complex that includes several viral proteins. The function of this machinery is essential for viral gene expression and viral re...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.5b00053
更新日期：2015-08-14 00:00:00
abstract：:Daptomycin is a lipopeptide antibiotic approved for use against Gram-positive organisms, including highly resistant species. A number of studies have suggested that daptomycin kills bacteria by membrane permeabilization and depolarization. Recently a model membrane system consisting of 1,2-dimyristoyl-sn-glycero-3-pho...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.6b00152
更新日期：2016-10-14 00:00:00
abstract：:We describe cross-reactive human antibodies recognizing influenza B viruses spanning nearly 80 years of antigenic drift. Structures show that they engage the receptor-binding site (RBS) of the viral hemagglutinin with strong similarities to their influenza A counterparts, despite structural differences between the RBS...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.0c00726
更新日期：2021-01-08 00:00:00
abstract：:The root cause of the antibiotic resistance crisis is the ability of bacteria to evolve resistance to a multitude of antibiotics and other environmental toxins. The regulation of adaptation is difficult to pinpoint due to extensive phenotypic heterogeneity arising during evolution. Here, we investigate the mechanisms ...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.5b00095
更新日期：2015-11-13 00:00:00
abstract：:Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different ...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.7b00020
更新日期：2017-07-14 00:00:00
abstract：:A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed for (i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites, ...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.9b00128
更新日期：2019-10-11 00:00:00
abstract：:The enzyme N-myristoyltransferase (NMT) catalyzes the essential fatty acylation of substrate proteins with myristic acid in eukaryotes and is a validated drug target in the parasite Trypanosoma brucei, the causative agent of African trypanosomiasis (sleeping sickness). N-Myristoylation typically mediates membrane loca...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.6b00034
更新日期：2016-06-10 00:00:00
abstract：:The Burkholderia cepacia complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are intrinsically resistant to many antibiotics and the lack of antibiotic development ne...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.7b00235
更新日期：2018-05-11 00:00:00
abstract：:Protein S-palmitoylation is an important post-translational modification (PTM) in blood stages of the malaria parasite, Plasmodium falciparum. S-palmitoylation refers to reversible covalent modification of cysteine residues of proteins by saturated fatty acids. In vivo, palmitoylation is regulated by concerted activit...
journal_title：ACS infectious diseases
pub_type： 杂志文章
doi：10.1021/acsinfecdis.9b00321
更新日期：2020-03-13 00:00:00
