Loss of β-Ketoacyl Acyl Carrier Protein Synthase III Activity Restores Multidrug-Resistant Escherichia coli Sensitivity to Previously Ineffective Antibiotics

Hong, Yaoqin; Qin, Jilong; Verderosa, Anthony D.; Hawas, Sophia; Zhang, Bing; Blaskovich, Mark A. T.; Cronan, John E.; Totsika, Makrina

doi:10.1128/msphere.00117-22

Cited by 7 publications

(3 citation statements)

References 67 publications

(77 reference statements)

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“…Reduction in membrane permeability is the leading cause of MDR to XDR in S. Typhi. , The antibiotics with a molecular weight (MW) around 600 Da can breach the outer membrane (OM) of Gram-negative organisms. In contrast, other drugs such as vancomycin (1449 Da) and daptomycin (1620 Da) have a MW above 1000 Da and have to pass through the bacterial cell wall through outer membrane proteins (OMPs) . OMPs such as OmpA, OmpF, OmpX, and LamB are critical barriers to the passage of small-size hydrophilic particles. , The hydrophilic class of antibiotics (β-lactams, aminoglycosides, etc.)…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, other drugs such as vancomycin (1449 Da) and daptomycin (1620 Da) have a MW above 1000 Da and have to pass through the bacterial cell wall through outer membrane proteins (OMPs). 13 OMPs such as OmpA, OmpF, OmpX, and LamB are critical barriers to the passage of small-size hydrophilic particles. 14,15 The hydrophilic class of antibiotics (β-lactams, aminoglycosides, etc.)…”

Section: ■ Introductionmentioning

confidence: 99%

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Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

Akshay,

Deekshit,

Mohan Raj

et al. 2023

ACS Infect. Dis.

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Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is Salmonella. The extensive and inappropriate treatments for Salmonella infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in Salmonella. Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in Salmonella. Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system’s differential expression and positional mutation in Salmonella may provide insight into developing strategic therapies for one health application.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

Akshay,

Deekshit,

Mohan Raj

et al. 2023

ACS Infect. Dis.

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“…The bacteria Escherichia coli and Streptococcus aureus have several crucial enzymes that can serve as drug targets, particularly β-ketoacyl-ACP synthase from Escherichia coli and TyrRS from Streptococcus aureus . β-ketoacyl-acyl carrier protein (ACP) synthases are the key regulators of fatty acid synthesis in Escherichia coli [ 15 , 16 ]. β-ketoacyl-ACP synthase is involved in condensation reactions during fatty acid biosynthesis [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Potency of an Active Compound from Sansevieria trifasciata Prain: An Integrated In Vitro and In Silico Study

Kasmawati,

Ruslin,

Arfan

et al. 2023

Molecules

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Sansevieria trifasciata Prain holds great potential as a valuable asset in pharmaceutical development. In this study, our focus is to explore and assess the antibacterial activity of various components derived from this plant, including extracts, fractions, subfractions, and isolates, explicitly targeting two common bacteria: Escherichia coli and Streptococcus aureus. The isolated compound, identified as a derivative pyridone alkaloid (5-methyl-11-(2-oxopyridin-1(2H)-yl)undecaneperoxoicacid), demonstrates notable antibacterial effects. The extracts, fractions, subfractions, and isolates reveal significant bacterial growth reductions (p < 0.05). The minimum inhibitory concentration (MIC) values for Escherichia coli were 1.95 ppm, 3.9 ppm, 15.62 ppm, and 7.81 ppm, respectively, while the MIC values for Streptococcus aureus were 1.95 ppm, 1.95 ppm, 15.62 ppm, and 7.81 ppm, respectively. Computational analysis showed the isolates’ interaction with key residues on the active site of β-ketoacyl-ACP synthase from Escherichia coli and TyrRS from Streptococcus aureus. The findings indicate that the isolates exhibit a strong affinity for specific residues, including His333, Cys163, and Phe392 in β-ketoacyl-ACP synthase, as well as Arg88, His117, Glu160, and Gln213 in TyrRS. Comparative energy calculations using MMPBSA demonstrate the isolates’ favorable binding energy (−104,101 kJ/mol for β-ketoacyl-ACP synthase and −81,060 kJ/mol for TyrRS) compared to ciprofloxacin. The elucidated antibacterial activity and molecular interactions of the isolates present valuable knowledge for future in vitro studies, facilitating the development of novel antibacterial agents targeting diverse bacterial strains.

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Target identification, and optimization of dioxygenated amide derivatives as potent antibacterial agents with FabH inhibitory activity

Chang,

Ji,

Zhu

et al. 2024

European Journal of Medicinal Chemistry

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Loss of β-Ketoacyl Acyl Carrier Protein Synthase III Activity Restores Multidrug-Resistant Escherichia coli Sensitivity to Previously Ineffective Antibiotics

Cited by 7 publications

References 67 publications

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

Antibacterial Potency of an Active Compound from Sansevieria trifasciata Prain: An Integrated In Vitro and In Silico Study

Target identification, and optimization of dioxygenated amide derivatives as potent antibacterial agents with FabH inhibitory activity

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