Instructive Advances in Chemical Microbiology Inspired by Nature's Diverse Inventory of Molecules.

Abstract:

:Natural product antibiotics have played an essential role in the treatment of bacterial infection in addition to serving as useful tools to explore the intricate biology of bacteria. Our current arsenal of antibiotics operate through the inhibition of well-defined bacterial targets critical for replication and growth. Pathogenic bacteria effectively utilize a diversity of mechanisms that lead to acquired resistance and/or innate tolerance toward antibiotic therapies, which can result in devastating consequences to human life. Several research groups have established innovative programs that work at the chemistry-biology interface to develop new molecules that aim to define and address concerns related to antibiotic resistance and tolerance. In this Review, we present recent progress by select research groups that highlight a diversity of integrated chemical biology and medicinal chemistry approaches aimed at the development and utilization of chemical tools that have led to promising new microbiological insights that may lead to significant clinical advances regarding the treatment of pathogenic bacteria.

journal_name

ACS Infect Dis

journal_title

ACS infectious diseases

authors

Liu K,Huigens RW 3rd

doi

10.1021/acsinfecdis.9b00413

subject

Has Abstract

pub_date

2020-04-10 00:00:00

pages

541-562

issue

4

issn

2373-8227

journal_volume

6

pub_type

杂志文章,评审
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  • Immunoassay for HIV Drug Metabolites Tenofovir and Tenofovir Diphosphate.

    abstract::Poor patient adherence to antiretroviral medication represents a major obstacle for managing disease and reducing rates of new HIV infections. The measurement of patient drug levels is the most objective method of determining adherence. Tenofovir and tenofovir diphosphate are metabolites of some of the most common HIV...

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    doi:10.1021/acsinfecdis.0c00010

    authors: Sevenler D,Bardon A,Fernandez Suarez M,Marshall L,Toner M,Drain PK,Sandlin RD

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  • Alternative Pathway to a Glycopeptide-Resistant Cell Wall in the Balhimycin Producer Amycolatopsis balhimycina.

    abstract::Balhimycin, a vancomycin-type glycopeptide, is a lipid II targeting antibiotic produced by Amycolatopsis balhimycina. A. balhimycina has developed a self-resistance mechanism based on the synergistic action of different enzymes resulting in modified peptidoglycan. The canonical resistance mechanism against glycopeptid...

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    authors: Frasch HJ,Kalan L,Kilian R,Martin T,Wright GD,Stegmann E

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  • Development of an Enzyme-Mediated, Site-Specific Method to Conjugate Toll-Like Receptor 2 Agonists onto Protein Antigens: Toward a Broadly Protective, Four Component, Group A Streptococcal Self-Adjuvanting Lipoprotein-Fusion Combination Vaccine.

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    doi:10.1021/acsinfecdis.0c00047

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  • 1,2,3-Triazolylmethaneboronate: A Structure Activity Relationship Study of a Class of β-Lactamase Inhibitors against Acinetobacter baumannii Cephalosporinase.

    abstract::Boronic acid transition state inhibitors (BATSIs) are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific BATSIs bearing an amide side chain mimicking the β-lactam's amide side chain are an established and recognized synthetic strategy. Herein, we describe a new cl...

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    authors: Caselli E,Fini F,Introvigne ML,Stucchi M,Taracila MA,Fish ER,Smolen KA,Rather PN,Powers RA,Wallar BJ,Bonomo RA,Prati F

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  • Toward Curative Immunomodulation Strategies for Chronic Hepatitis B Virus Infection.

    abstract::Chronic hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality worldwide. HBV surface antigen loss is considered a functional cure and is an ideal goal for antiviral therapy. However, current treatment regimens, including nucleos(t)ide analogues or interferons monotherapy and combination th...

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    doi:10.1021/acsinfecdis.8b00297

    authors: Zhu W,Liu H,Zhang X

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  • Chemical Control of Quorum Sensing in E. coli: Identification of Small Molecule Modulators of SdiA and Mechanistic Characterization of a Covalent Inhibitor.

    abstract::Enterohemorrhagic Escherichia coli (EHEC) is the causative agent of severe diarrheal disease in humans. Cattle are the natural reservoir of EHEC, and approximately 75% of EHEC infections in humans stem from bovine products. Many common bacterial pathogens, including EHEC, rely on chemical communication systems, such a...

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    doi:10.1021/acsinfecdis.0c00654

    authors: Styles MJ,Early SA,Tucholski T,West KHJ,Ge Y,Blackwell HE

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  • Probing the Interaction of Aspergillomarasmine A with Metallo-β-lactamases NDM-1, VIM-2, and IMP-7.

    abstract::Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively ...

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    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.7b00106

    authors: Bergstrom A,Katko A,Adkins Z,Hill J,Cheng Z,Burnett M,Yang H,Aitha M,Mehaffey MR,Brodbelt JS,Tehrani KHME,Martin NI,Bonomo RA,Page RC,Tierney DL,Fast W,Wright GD,Crowder MW

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  • N-Myristoylation as a Drug Target in Malaria: Exploring the Role of N-Myristoyltransferase Substrates in the Inhibitor Mode of Action.

    abstract::Malaria continues to be a significant cause of death and morbidity worldwide, and there is a need for new antimalarial drugs with novel targets. We have focused as a potential target for drug development on N-myristoyl transferase (NMT), an enzyme that acylates a wide range of substrate proteins. The NMT substrates in...

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    pub_type: 杂志文章,评审

    doi:10.1021/acsinfecdis.7b00203

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  • Preclinical Antiviral Testing for Dengue Virus Infection in Mouse Models and Its Association with Clinical Studies.

    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...

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    pub_type: 杂志文章,评审

    doi:10.1021/acsinfecdis.8b00054

    authors: Watanabe S,Low JG,Vasudevan SG

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  • Nerve Growth Factor Confers Neuroprotection against Colistin-Induced Peripheral Neurotoxicity.

    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...

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    doi:10.1021/acsinfecdis.0c00107

    authors: Dai C,Xiong J,Wang Y,Shen J,Velkov T,Xiao X

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  • Plasma Levels of Complement Factor I and C4b Peptides Are Associated with HIV Suppression.

    abstract::Individuals who exhibit long-term HIV suppression and CD4 T-cell preservation without antiretroviral therapy are of great interest for HIV research. There is currently no robust method for rapid identification of these "HIV controller" subjects; however, HLA-B*57 (human leukocyte antigen (major histocompatibility comp...

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    doi:10.1021/acsinfecdis.7b00042

    authors: Wu B,Ouyang Z,Lyon CJ,Zhang W,Clift T,Bone CR,Li B,Zhao Z,Kimata JT,Yu XG,Hu Y

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  • Targeted Inhibition of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 with a Constrained J Domain-Derived Disruptor Peptide.

    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...

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    authors: Flaherty BR,Ho TG,Schmidt SH,Herberg FW,Peterson DS,Kennedy EJ

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  • Development of Antibiotics That Dysregulate the Neisserial ClpP Protease.

    abstract::Evolving antimicrobial resistance has motivated the search for novel targets and alternative therapies. Caseinolytic protease (ClpP) has emerged as an enticing new target since its function is conserved and essential for bacterial fitness, and because its inhibition or dysregulation leads to bacterial cell death. ClpP...

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    doi:10.1021/acsinfecdis.0c00599

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  • Identification of Trypanosoma brucei AdoMetDC Inhibitors Using a High-Throughput Mass Spectrometry-Based Assay.

    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...

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    doi:10.1021/acsinfecdis.7b00022

    authors: Volkov OA,Cosner CC,Brockway AJ,Kramer M,Booker M,Zhong S,Ketcherside A,Wei S,Longgood J,McCoy M,Richardson TE,Wring SA,Peel M,Klinger JD,Posner BA,De Brabander JK,Phillips MA

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  • Gene Expression Variability Underlies Adaptive Resistance in Phenotypically Heterogeneous Bacterial Populations.

    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 ...

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    doi:10.1021/acsinfecdis.5b00095

    authors: Erickson KE,Otoupal PB,Chatterjee A

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  • Daptomycin Leakage Is Selective.

    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...

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    doi:10.1021/acsinfecdis.6b00152

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  • REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control of HBV and HDV Infection.

    abstract::Nucleic acid polymers (NAPs) are broad spectrum antiviral agents whose antiviral activity in hepatitis B virus (HBV) infection is derived from their ability to block the release of the hepatitis B virus surface antigen (HBsAg). This pharmacological activity blocks replenishment of HBsAg in the circulation, allowing ho...

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    doi:10.1021/acsinfecdis.8b00156

    authors: Vaillant A

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  • Discovery and Mechanistic Study of a Novel Human-Stimulator-of-Interferon-Genes Agonist.

    abstract::Stimulator of interferon genes (STING) is an integral ER-membrane protein that can be activated by 2'3'-cGAMP synthesized by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) upon binding of double-stranded DNA. It activates interferon (IFN) and inflammatory cytokine responses to defend against in...

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    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.9b00010

    authors: Zhang X,Liu B,Tang L,Su Q,Hwang N,Sehgal M,Cheng J,Ma J,Zhang X,Tan Y,Zhou Y,Duan Z,DeFilippis VR,Viswanathan U,Kulp J,Du Y,Guo JT,Chang J

    更新日期:2019-07-12 00:00:00

  • Illicit Transport via Dipeptide Transporter Dpp is Irrelevant to the Efficacy of Negamycin in Mouse Thigh Models of Escherichia coli Infection.

    abstract::Negamycin is a hydrophilic antimicrobial translation inhibitor that crosses the lipophilic inner membrane of Escherichia coli via at least two transport routes to reach its intracellular target. In a minimal salts medium, negamycin's peptidic nature allows illicit entry via a high-affinity route by hijacking the Dpp d...

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    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.5b00027

    authors: McKinney DC,Bezdenejnih-Snyder N,Farrington K,Guo J,McLaughlin RE,Ruvinsky AM,Singh R,Basarab GS,Narayan S,Buurman ET

    更新日期:2015-05-08 00:00:00

  • Diaza-anthracene Antibiotics from a Freshwater-Derived Actinomycete with Selective Antibacterial Activity toward Mycobacterium tuberculosis.

    abstract::Multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis are resistant to first- and second-line drug regimens and resulted in 210,000 fatalities in 2013. In the current study, we screened a library of aquatic bacterial natural product fractions for their ability to inhibit this pathogen. A frac...

    journal_title:ACS infectious diseases

    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.5b00005

    authors: Mullowney MW,Hwang CH,Newsome AG,Wei X,Tanouye U,Wan B,Carlson S,Barranis NJ,hAinmhire E,Chen WL,Krishnamoorthy K,White J,Blair R,Lee H,Burdette JE,Rathod PK,Parish T,Cho S,Franzblau SG,Murphy BT

    更新日期:2015-04-10 00:00:00

  • Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri.

    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

    authors: Anwar A,Mungroo MR,Anwar A,Sullivan WJ Jr,Khan NA,Siddiqui R

    更新日期:2019-12-13 00:00:00

  • Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential.

    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

    authors: Xu J,Shi PY,Li H,Zhou J

    更新日期:2020-05-08 00:00:00

  • Porphyromonas gingivalis Infection Promoted the Proliferation of Oral Squamous Cell Carcinoma Cells through the miR-21/PDCD4/AP-1 Negative Signaling Pathway.

    abstract::Recent epidemiological studies have revealed that Porphyromonas gingivalis, a major pathogen in periodontal disease, is associated with the development of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gi...

    journal_title:ACS infectious diseases

    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.9b00032

    authors: Chang C,Wang H,Liu J,Pan C,Zhang D,Li X,Pan Y

    更新日期:2019-08-09 00:00:00

  • Biochemical Characterization of Respiratory Syncytial Virus RNA-Dependent RNA Polymerase Complex.

    abstract::RNA-dependent RNA polymerases (RdRPs) from nonsegmented negative strand (NNS) RNA viruses perform both mRNA transcription and genome replication, and these activities are regulated by their interactions with RNA and other accessory proteins within the ribonucleoprotein (RNP) complex. Detailed biochemical characterizat...

    journal_title:ACS infectious diseases

    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.0c00554

    authors: Balakrishnan A,Price E,Luu C,Shaul J,Wartchow C,Cantwell J,Vo T,DiDonato M,Spraggon G,Hekmat-Nejad M

    更新日期:2020-10-09 00:00:00

  • A Target-Based Whole Cell Screen Approach To Identify Potential Inhibitors of Mycobacterium tuberculosis Signal Peptidase.

    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

    authors: Bonnett SA,Ollinger J,Chandrasekera S,Florio S,O'Malley T,Files M,Jee JA,Ahn J,Casey A,Ovechkina Y,Roberts D,Korkegian A,Parish T

    更新日期:2016-12-09 00:00:00

  • Investigations into the Antibacterial Mechanism of Action of Viridicatumtoxins.

    abstract::Viridicatumtoxins are a rare class of tetracycline-like antibiotics that strongly inhibit drug-resistant Gram-positive bacteria. Although reported to exhibit in vitro inhibition activity to undecaprenyl pyrophosphate synthase (UPPS), an essential enzyme in bacterial cell wall synthesis, the biological targets and mech...

    journal_title:ACS infectious diseases

    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.0c00031

    authors: Li W,Li L,Zhang C,Cai Y,Gao Q,Wang F,Cao Y,Lin J,Li J,Shang Z,Lin W

    更新日期:2020-07-10 00:00:00

  • Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

    abstract::Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgenc...

    journal_title:ACS infectious diseases

    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.7b00211

    authors: Chaparro MJ,Calderón F,Castañeda P,Fernández-Alvaro E,Gabarró R,Gamo FJ,Gómez-Lorenzo MG,Martín J,Fernández E

    更新日期:2018-04-13 00:00:00

  • Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients.

    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

    authors: Papp-Wallace KM,Becka SA,Zeiser ET,Ohuchi N,Mojica MF,Gatta JA,Falleni M,Tosi D,Borghi E,Winkler ML,Wilson BM,LiPuma JJ,Nukaga M,Bonomo RA

    更新日期:2017-07-14 00:00:00

  • Substrate Tolerance of Bacterial Glycosyltransferase MurG: Novel Fluorescence-Based Assays.

    abstract::MurG (uridine diphosphate-N-acetylglucosamine/N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase) is an essential bacterial glycosyltransferase that catalyzes the N-acetylglucosamine (GlcNAc) transformation of lipid I to lipid II during peptidoglycan biosynthesis. Park's nucleot...

    journal_title:ACS infectious diseases

    pub_type: 杂志文章

    doi:10.1021/acsinfecdis.9b00242

    authors: Mitachi K,Yun HG,Gillman CD,Skorupinska-Tudek K,Swiezewska E,Clemons WM Jr,Kurosu M

    更新日期:2020-06-12 00:00:00