Exploring Additional Dimensions of Complexity in Inhibitor Design for Serine β-Lactamases: Mechanistic and Intra- and Inter-molecular Chemistry Approaches.

Abstract:

:As a bacterial resistance strategy, serine β-lactamases have evolved from cell wall synthesizing enzymes known as penicillin-binding proteins (PBP), by not only covalently binding β-lactam antibiotics but, also acquiring mechanisms of deacylating these antibiotics. This critical deacylation step leads to release of hydrolyzed and inactivated β-lactams, thereby providing resistance for the bacteria against these antibiotics targeting the cell wall. To combat β-lactamase-mediated antibiotic resistance, numerous β-lactamase inhibitors were developed that utilize various strategies to inactivate the β-lactamase. Most of these compounds are "mechanism-based" inhibitors that in some manner mimic the β-lactam substrate, having a carbonyl moiety and a negatively charged carboxyl or sulfate group. These compounds form a covalent adduct with the catalytic serine via an initial acylation step. To increase the life-time of the inhibitory covalent adduct intermediates, a remarkable array of different strategies was employed to improve inhibition potency. Such approaches include post-acylation intra- and intermolecular chemical rearrangements as well as affecting the deacylation water. These approaches transform the inhibitor design process from a 3-dimensional problem (i.e., XYZ coordinates) to one with additional dimensions of complexity as the reaction coordinate and time spent at each chemical state need to be taken into consideration. This review highlights the mechanistic intricacies of the design efforts of the β-lactamase inhibitors which so far have resulted in the development of "two generations" and 5 clinically available inhibitors.

journal_name

Front Microbiol

authors

van den Akker F,Bonomo RA

doi

10.3389/fmicb.2018.00622

subject

Has Abstract

pub_date

2018-04-05 00:00:00

pages

622

issn

1664-302X

journal_volume

9

pub_type

杂志文章,评审
  • Avian Paramyxovirus Type-3 as a Vaccine Vector: Identification of a Genome Location for High Level Expression of a Foreign Gene.

    abstract::Avian paramyxovirus serotype 3 (APMV-3) causes infection in a wide variety of avian species, but it does not cause apparent diseases in chickens. On the contrary, APMV-1, also known as Newcastle disease virus (NDV), can cause severe disease in chickens. Currently, natural low virulence strains of NDV are used as live-...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2017.00693

    authors: Yoshida A,Samal SK

    更新日期:2017-04-20 00:00:00

  • Molecular Mechanisms of Colistin Resistance in Klebsiella pneumoniae Causing Bacteremia from India-A First Report.

    abstract::Colistin has long been a reserve drug used for the treatment of carbapenem resistant Klebsiella pneumoniae. Carbapenem resistance in K. pneumoniae has been increasing and is as high as 44% in India. Although a reserve agent, with rise in rates of resistance to carbapenems, the usage of colistin has increased over the ...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2016.02135

    authors: Pragasam AK,Shankar C,Veeraraghavan B,Biswas I,Nabarro LE,Inbanathan FY,George B,Verghese S

    更新日期:2017-01-09 00:00:00

  • Recent Advances in the Recombinant Biosynthesis of Polyphenols.

    abstract::Plants are the source of various natural compounds with pharmaceutical and nutraceutical importance which have shown numerous health benefits with relatively fewer side effects. However, extraction of these compounds from native producers cannot meet the ever-increasing demands of the growing population due to, among ...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fmicb.2017.02259

    authors: Chouhan S,Sharma K,Zha J,Guleria S,Koffas MAG

    更新日期:2017-11-16 00:00:00

  • Identification of XylR, the Activator of Arabinose/Xylose Inducible Regulon in Sulfolobus acidocaldarius and Its Application for Homologous Protein Expression.

    abstract::The thermophilic archaeon Sulfolobus acidocaldarius can use different carbon sources for growth, including the pentoses D-xylose and L-arabinose. In this study, we identified the activator XylR (saci_2116) responsible for the transcriptional regulation of the pentose transporter and pentose metabolizing genes in S. ac...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2020.01066

    authors: van der Kolk N,Wagner A,Wagner M,Waßmer B,Siebers B,Albers SV

    更新日期:2020-05-26 00:00:00

  • Genetic and Toxigenic Variability within Aspergillus flavus Population Isolated from Maize in Two Diverse Environments in Kenya.

    abstract::Aspergillus flavus is the main producer of carcinogenic aflatoxins in agricultural commodities such as maize. This fungus occurs naturally on crops, and produces aflatoxins when environmental conditions are favorable. The aim of this study is to analyse the genetic variability among 109 A. flavus isolates previously r...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2018.00057

    authors: Okoth S,De Boevre M,Vidal A,Diana Di Mavungu J,Landschoot S,Kyallo M,Njuguna J,Harvey J,De Saeger S

    更新日期:2018-01-26 00:00:00

  • Characterization of Microbial Dynamics and Volatile Metabolome Changes During Fermentation of Chambourcin Hybrid Grapes From Two Pennsylvania Regions.

    abstract::Microbial diversity present on grapes in wineries, and throughout fermentation has been associated with important metabolites for final wine quality. Although microbiome-metabolome associations have been well characterized and could be used as indicators of wine quality, the impact of regionality on the microbiome and...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2020.614278

    authors: Wang HL,Hopfer H,Cockburn DW,Wee J

    更新日期:2021-01-11 00:00:00

  • Separating the Empirical Wheat From the Pseudoscientific Chaff: A Critical Review of the Literature Surrounding Glyphosate, Dysbiosis and Wheat-Sensitivity.

    abstract::The prevalence of digestive disorders has increased globally, as countries have adopted a more "Westernized" diet pattern. A Western diet, characterized as high in fat and refined carbohydrates, can also be defined as a product of increased technology and industrialization. Modern farmers rely on agrochemicals to meet...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fmicb.2020.556729

    authors: Barnett JA,Gibson DL

    更新日期:2020-09-25 00:00:00

  • You Can't B. cereus - A Review of Bacillus cereus Strains That Cause Anthrax-Like Disease.

    abstract::Emerging strains of Bacillus cereus, traditionally considered a self-limiting foodborne pathogen, have been associated with anthrax-like disease in mammals, including humans. The strains have emerged by divergent evolution and, as exchange of genetic material in the Bacillus genus occurs naturally, it is possible that...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fmicb.2020.01731

    authors: Baldwin VM

    更新日期:2020-08-19 00:00:00

  • MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis.

    abstract::Currently microorganisms are best identified using 16S rRNA and 18S rRNA gene sequencing. However, in recent years matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a potential tool for microbial identification and diagnosis. During the MALDI-TOF MS process, mic...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fmicb.2015.00791

    authors: Singhal N,Kumar M,Kanaujia PK,Virdi JS

    更新日期:2015-08-05 00:00:00

  • Bacteriophage Infectivity Against Pseudomonas aeruginosa in Saline Conditions.

    abstract::Pseudomonas aeruginosa is a ubiquitous member of marine biofilm, and reduces thiosulfate to produce toxic hydrogen sulfide gas. In this study, lytic bacteriophages were isolated and applied to inhibit the growth of P. aeruginosa in planktonic mode at different temperature, pH, and salinity. Bacteriophages showed optim...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2018.00875

    authors: Scarascia G,Yap SA,Kaksonen AH,Hong PY

    更新日期:2018-05-02 00:00:00

  • Transcriptome Analysis Reveals the Flexibility of Cordycepin Network in Cordyceps militaris Activated by L-Alanine Addition.

    abstract::Cordycepin, isolated from the traditional medicinal fungus Cordyceps militaris, has gained much attention due to its various clinical functions. Previous reports of L-alanine addition could significantly improve cordycepin production, but the molecular mechanism remains unknown. In this study, transcriptome analysis o...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2020.00577

    authors: Chen BX,Wei T,Xue LN,Zheng QW,Ye ZW,Zou Y,Yang Y,Yun F,Guo LQ,Lin JF

    更新日期:2020-04-24 00:00:00

  • Cell Wall-Associated Virulence Factors Contribute to Increased Resilience of Old Cryptococcus neoformans Cells.

    abstract::As Cryptococcus neoformans mother cells generationally age, their cell walls become thicker and cell-wall associated virulence factors are upregulated. Antiphagocytic protein 1 (App1), and laccase enzymes (Lac1 and Lac2) are virulence factors known to contribute to virulence of C. neoformans during infection through i...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2019.02513

    authors: Orner EP,Bhattacharya S,Kalenja K,Hayden D,Del Poeta M,Fries BC

    更新日期:2019-11-07 00:00:00

  • Malate-Dependent Carbon Utilization Enhances Central Metabolism and Contributes to Biological Fitness of Laribacter hongkongensis via CRP Regulation.

    abstract::Metabolic adaptation in various environmental niches is crucial for bacterial extracellular survival and intracellular replication during infection. However, the metabolism of carbon/nitrogen sources and related regulatory mechanisms in Laribacter hongkongensis, an asaccharolytic bacterium associated with invasive inf...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2019.01991

    authors: Xiong L,Chan E,Teng JLL,Liu S,Lau SKP,Woo PCY

    更新日期:2019-08-28 00:00:00

  • High-Throughput Sequence Analyses of Bacterial Communities and Multi-Mycotoxin Profiling During Processing of Different Formulations of Kunu, a Traditional Fermented Beverage.

    abstract::Kunu is a traditional fermented single or mixed cereals-based beverage popularly consumed in many parts of West Africa. Presently, the bacterial community and mycotoxin contamination profiles during processing of various kunu formulations have never been comprehensively studied. This study, therefore, investigated the...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2018.03282

    authors: Ezekiel CN,Ayeni KI,Ezeokoli OT,Sulyok M,van Wyk DAB,Oyedele OA,Akinyemi OM,Chibuzor-Onyema IE,Adeleke RA,Nwangburuka CC,Hajšlová J,Elliott CT,Krska R

    更新日期:2019-01-09 00:00:00

  • The Responses of Germ-Free Zebrafish (Danio rerio) to Varying Bacterial Concentrations, Colonization Time Points, and Exposure Duration.

    abstract::Colonizing germ-free (GF) zebrafish with specific bacterial species provides the possibility of understanding the influence on host biological processes including gene expression, development, immunity, and behavioral responses. It also enlightens our understanding on the host-microbe interactions within the physiolog...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2019.02156

    authors: Tan F,Limbu SM,Qian Y,Qiao F,Du ZY,Zhang M

    更新日期:2019-09-18 00:00:00

  • Bacterial Microcompartment-Dependent 1,2-Propanediol Utilization Stimulates Anaerobic Growth of Listeria monocytogenes EGDe.

    abstract::Bacterial microcompartments (BMCs) are proteinaceous organelles that optimize specific metabolic pathways referred to as metabolosomes involving transient production of toxic volatile metabolites such as aldehydes. Previous bioinformatics analysis predicted the presence of BMCs in 23 bacterial phyla including foodborn...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2019.02660

    authors: Zeng Z,Smid EJ,Boeren S,Notebaart RA,Abee T

    更新日期:2019-11-15 00:00:00

  • Spring thaw ionic pulses boost nutrient availability and microbial growth in entombed Antarctic Dry Valley cryoconite holes.

    abstract::The seasonal melting of ice entombed cryoconite holes on McMurdo Dry Valley glaciers provides oases for life in the harsh environmental conditions of the polar desert where surface air temperatures only occasionally exceed 0°C during the Austral summer. Here we follow temporal changes in cryoconite hole biogeochemistr...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2014.00694

    authors: Telling J,Anesio AM,Tranter M,Fountain AG,Nylen T,Hawkings J,Singh VB,Kaur P,Musilova M,Wadham JL

    更新日期:2014-12-11 00:00:00

  • Effects of Lactobacillus fermentum CQPC04 on Lipid Reduction in C57BL/6J Mice.

    abstract::Probiotics are functional foods that can effectively regulate lipid reduction and maintain body health. In this study, a strain of Lactobacillus fermentum CQPC04 (LF-CQPC04) isolated from traditional naturally fermented vegetables (Sichuan pickles) was studied, and its effects on lipid reduction in mice, as well as it...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2020.573586

    authors: Yi R,Tan F,Zhou X,Mu J,Li L,Du X,Yang Z,Zhao X

    更新日期:2020-09-03 00:00:00

  • A Historical Review on Antibiotic Resistance of Foodborne Campylobacter.

    abstract::Campylobacter is one of the most commonly reported foodborne human bacterial gastrointestinal pathogens. Campylobacter is the etiological agent of campylobacteriosis, which is generally a self-limited illness and therefore does not require treatment. However, when patients are immunocompromised or have other co-morbid...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fmicb.2019.01509

    authors: Yang Y,Feye KM,Shi Z,Pavlidis HO,Kogut M,J Ashworth A,Ricke SC

    更新日期:2019-07-26 00:00:00

  • Microbial Communities in a High Arctic Polar Desert Landscape.

    abstract::The High Arctic is dominated by polar desert habitats whose microbial communities are poorly understood. In this study, we used next generation sequencing to describe the α- and β-diversity of microbial communities in polar desert soils from the Kongsfjorden region of Svalbard. Ten phyla dominated the soils and accoun...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2016.00419

    authors: McCann CM,Wade MJ,Gray ND,Roberts JA,Hubert CR,Graham DW

    更新日期:2016-03-31 00:00:00

  • Viral Induced Microbial Mortality in Arctic Hypersaline Spring Sediments.

    abstract::Viruses are a primary influence on microbial mortality in the global ocean. The impacts of viruses on their microbial hosts in low-energy environments are poorly explored and are the focus of this study. To investigate the role of viruses in mediating mortality in low-energy environments where contacts between viruses...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2016.02158

    authors: Colangelo-Lillis J,Wing BA,Raymond-Bouchard I,Whyte LG

    更新日期:2017-01-23 00:00:00

  • Genomic Characterization of Extended-Spectrum Cephalosporin-Resistant Salmonella enterica in the Colombian Poultry Chain.

    abstract::Salmonella enterica serovars have been isolated from Colombian broilers and broiler meat. The aim of this study was to investigate the diversity of ESBL/pAmpC genes in extended-spectrum cephalosporin resistant Salmonella enterica and the phylogeny of ESBL/pAmpC-carrying Salmonella using Whole Genome Sequencing (WGS). ...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2018.02431

    authors: Castellanos LR,van der Graaf-van Bloois L,Donado-Godoy P,León M,Clavijo V,Arévalo A,Bernal JF,Mevius DJ,Wagenaar JA,Zomer A,Hordijk J

    更新日期:2018-10-26 00:00:00

  • Influence of Catecholamines (Epinephrine/Norepinephrine) on Biofilm Formation and Adhesion in Pathogenic and Probiotic Strains of Enterococcus faecalis.

    abstract::Enterococcus faecalis has controversial status due to its emerging role in nosocomial infections, while some strains with beneficial effects are used as probiotics and starter cultures in dairy industry. These bacteria can be found as resident or transient germs in the gut or on skin, where they are continually expose...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2020.01501

    authors: Cambronel M,Nilly F,Mesguida O,Boukerb AM,Racine PJ,Baccouri O,Borrel V,Martel J,Fécamp F,Knowlton R,Zimmermann K,Domann E,Rodrigues S,Feuilloley M,Connil N

    更新日期:2020-07-24 00:00:00

  • Assessment of the Microbiome and Potential Aflatoxin Associated With the Medicinal Herb Platycladus orientalis.

    abstract::Platycladi Semen, which is derived from the dried ripe seed of Platycladus orientalis, has been used for the treatment of insomnia and constipation in China for 2000 years. However, it is susceptible to fungal and aflatoxin contamination under proper humidity and temperature during storage. Although aflatoxin contamin...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2020.582679

    authors: Yu J,Guo M,Jiang W,Yang M,Pang X

    更新日期:2020-10-23 00:00:00

  • Actin and DNA Protect Histones from Degradation by Bacterial Proteases but Inhibit Their Antimicrobial Activity.

    abstract::Histones are small polycationic proteins located in the cell nucleus. Together, DNA and histones are integral constituents of the nucleosomes. Upon apoptosis, necrosis, and infection - induced cell death, histones are released from the cell. The extracellular histones have strong antimicrobial activity but are also cy...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2016.01248

    authors: Sol A,Skvirsky Y,Blotnick E,Bachrach G,Muhlrad A

    更新日期:2016-08-09 00:00:00

  • Bacterial Catabolism of Dimethylsulfoniopropionate (DMSP).

    abstract::Dimethylsulfoniopropionate (DMSP) is a metabolite produced primarily by marine phytoplankton and is the main precursor to the climatically important gas dimethylsulfide (DMS). DMS is released upon bacterial catabolism of DMSP, but it is not the only possible fate of DMSP sulfur. An alternative demethylation/demethiola...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2011.00172

    authors: Reisch CR,Moran MA,Whitman WB

    更新日期:2011-08-12 00:00:00

  • Salmonella Interaction with and Passage through the Intestinal Mucosa: Through the Lens of the Organism.

    abstract::Salmonella enterica serotypes are invasive enteric pathogens spread through fecal contamination of food and water sources, and represent a constant public health threat around the world. The symptoms associated with salmonellosis and typhoid disease are largely due to the host response to invading Salmonella, and to t...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2011.00088

    authors: Hallstrom K,McCormick BA

    更新日期:2011-04-29 00:00:00

  • The Developmental Stage Symbionts of the Pea Aphid-Feeding Chrysoperla sinica (Tjeder).

    abstract::Chrysoperla sinica (Tjeder) is widely recognized as an important holometabolous natural enemy of various insect pests in different cropping systems and as a non-target surrogate in environmental risk assessment of Bt rice (i.e., genetically modified rice to express a toxin gene from Bacillus thuringiensis). Like other...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2019.02454

    authors: Zhao C,Zhao H,Zhang S,Luo J,Zhu X,Wang L,Zhao P,Hua H,Cui J

    更新日期:2019-11-01 00:00:00

  • Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo.

    abstract::Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms i...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2017.00906

    authors: Ñahui Palomino RA,Zicari S,Vanpouille C,Vitali B,Margolis L

    更新日期:2017-05-19 00:00:00

  • Pedunculate Oaks (Quercus robur L.) Differing in Vitality as Reservoirs for Fungal Biodiversity.

    abstract::Ecological significance of trees growing in urban and peri-urban settings is likely to increase in future land-use regimes, calling for better understanding of their role as potential reservoirs or stepping stones for associated biodiversity. We studied the diversity of fungal endophytes in woody tissues of asymptomat...

    journal_title:Frontiers in microbiology

    pub_type: 杂志文章

    doi:10.3389/fmicb.2018.01758

    authors: Agostinelli M,Cleary M,Martín JA,Albrectsen BR,Witzell J

    更新日期:2018-08-03 00:00:00