Tung Tran

Inhibiting Amikacin Resistance in Multidrug-Resistant Bacteria with Cadmium and Pyrithione

Angel J. Magaña, David Chek Ling Ngo, Kenneth Burgos, Carolina Dominguez Maldonado et autres

Abstract The ongoing antibiotic resistance crisis is one of the most pressing public health challenges. Multidrug-resistant bacterial pathogens are reaching the point where some are becoming untreatable. Consequently, besides discovering novel antibiotics, alternative strategies must be explored to manage the problem. One …

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P-1346. Identification of aminoglycoside 6′-N-acetyltransferase type Ib small molecule inhibitors using mixture-based combinatorial libraries and structure-activity relationship studies

Jan Sklenicka, Tung Tran, Angel J. Magaña, María Soledad Ramirez et autres

Abstract Background The aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6’)-Ib] confers resistance to amikacin and other relevant aminoglycosides in Gram-negatives. To identify small molecule inhibitors of AAC(6’)-Ib that would overcome resistance, we utilized a strategy incorporating mixture-based combinatorial libraries, scaffold ranking, and positional scanning, …

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Inhibition of Aminoglycoside 6′-N-Acetyltransferase Type Ib-Mediated Amikacin Resistance in Multidrug- and Carbapenem-Resistant Clinical Strains by Cadmium in Combination with Pyrithione

Angel J. Magaña, David Chek Ling Ngo, Kenneth Burgos, Carolina Dominguez Maldonado et autres

The ongoing antibiotic resistance crisis is among the most pressing public health chal-lenges. The rise and dissemination of multidrug-resistant bacterial pathogens is reaching the point when some become untreatable. Consequently, besides discovering novel antibiotics, alternative strategies must be explored to manage the …

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Structure–Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6′-N-Acetyltransferase Type Ib

Jan Sklenicka, Tung Tran, María Soledad Ramirez, Haley M. Donow et autres

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6′-N-acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome …

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Structure-activity relationship of pyrrolidine pentamine derivatives as inhibitors of the aminoglycoside 6′- N -acetyltransferase type Ib

Jan Sklenicka, Tung Tran, María Soledad Ramirez, Haley M. Donow et autres

Abstract Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by aminoglycoside 6′- N -acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way …

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Dynamics and quantitative contribution of the aminoglycoside 6′- N -acetyltransferase type Ib to amikacin resistance

Ophélie d’Udekem d’Acoz, Fong Hue, Tianyi Ye, Louise Wang et autres

ABSTRACT Aminoglycosides are essential components in the available armamentarium to treat bacterial infections. The surge and rapid dissemination of resistance genes strongly reduce their efficiency, compromising public health. Among the multitude of modifying enzymes that confer resistance to aminoglycosides, the aminoglycoside 6′- …

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Dynamics and quantitative contribution of the aminoglycoside 6′- N -acetyltransferase type Ib [AAC(6′)-Ib] to amikacin resistance

Ophélie d’Udekem d’Acoz, Fong Hue, Tianyi Ye, Louise Wang et autres

Abstract Aminoglycosides are essential components in the available armamentarium to treat bacterial infections. The surge and rapid dissemination of resistance genes strongly reduce their efficiency, compromising public health. Among the multitude of modifying enzymes that confer resistance to aminoglycosides, the aminoglycoside acetyltransferase …

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Measuring the Effective Lung Volume, Deadspace Volume and Ventilatory Heterogeneity at the Bedside Using the Inspired Sinewave Technique in ARDS Animal Model

Minh C. Tran, Douglas C. Crockett, Richard Bruce, Sophie Taylor et autres

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Inhibition of Enzymatic Acetylation-Mediated Resistance to Plazomicin by Silver Ions

David Chek Ling Ngo, Angel J. Magaña, Tung Tran, Jan Sklenicka et autres

Plazomicin is a recent U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6′ position. These substitutions produced a …

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Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions

Craig Reeves, Jesus Magallón, Kenneth Rocha, Tung Tran et autres

Clinical resistance to amikacin and other aminoglycosides is usually due to the enzymatic acetylation of the antimicrobial molecule. A ubiquitous resistance enzyme among Gram-negatives is the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], which catalyzes acetylation using acetyl-CoA as a donor substrate. Therapies that …

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Aminoglycoside 6'-N-Acetyltransferase Type Ib [Aac(6')-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions

Craig Reeves, Jesus Magallón, Kenneth Rocha, Tung Tran et autres

Clinical resistance to amikacin and other aminoglycosides is usually due to the enzymatic acetylation of the antimicrobial molecule. A ubiquitous resistance enzyme among Gram-negatives is the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], which catalyzes acetylation using acetyl-CoA as a donor substrate. Therapies that …

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Restoration of susceptibility to amikacin by 8-hydroxyquinoline analogs complexed to zinc

Jesus Magallón, Kevin Chiem, Tung Tran, María Soledad Ramirez et autres

Gram-negative pathogens resistant to amikacin and other aminoglycosides of clinical relevance usually harbor the 6'-N-acetyltransferase type Ib [AAC(6')-Ib], an enzyme that catalyzes inactivation of the antibiotic by acetylation using acetyl-CoA as donor substrate. Inhibition of the acetylating reaction could be a way …

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