Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria

Luna, Brian; Ershova, Ksenia; Yan, Jun; Ulhaq, Amber; Nielsen, Thor B.; Hsieh, Sarah; Paul, Pascale; VanScoy, Brian; Ambrose, Paul G.; Rudin, Sue; Hujer, Kristine M.; Actis, Luis A.; Skaar, Eric P.; Spellberg, Brad

doi:10.1093/jac/dkz225

Cited by 16 publications

(19 citation statements)

References 30 publications

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“…Both compounds can inhibit the formation of biofilms in P. aeruginosa [ 58 , 59 , 60 ]. Their in vitro activity against S. aureus , A. baumannii , K. pneumoniae and C. albicans has also been described [ 61 , 62 ]. However, some pathogens, such as P. aeruginosa , are able to use these proteins as an iron source [ 63 ], which limits their efficacy as antimicrobials against these microorganisms.…”

Section: Iron Chelators As Antimicrobial Agentsmentioning

confidence: 99%

Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections

Vinuesa

McConnell

2021

IJMS

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Iron is essential for multiple bacterial processes and is thus required for host colonization and infection. The antimicrobial activity of multiple iron chelators and gallium-based therapies against different bacterial species has been characterized in preclinical studies. In this review, we provide a synthesis of studies characterizing the antimicrobial activity of the major classes of iron chelators (hydroxamates, aminocarboxylates and hydroxypyridinones) and gallium compounds. Special emphasis is placed on recent in-vitro and in-vivo studies with the novel iron chelator DIBI. Limitations associated with iron chelation and gallium-based therapies are presented, with emphasis on limitations of preclinical models, lack of understanding regarding mechanisms of action, and potential host toxicity. Collectively, these studies demonstrate potential for iron chelators and gallium to be used as antimicrobial agents, particularly in combination with existing antibiotics. Additional studies are needed in order to characterize the activity of these compounds under physiologic conditions and address potential limitations associated with their clinical use as antimicrobial agents.

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Section: Iron Chelators As Antimicrobial Agentsmentioning

confidence: 99%

Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections

Vinuesa

McConnell

2021

IJMS

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“…The results showed that DMC has the ability to prevent MRSA from growth and suggested the potential of DMC to be further studied as an antibacterial agent. The kill kinetics of antimicrobial activity provides more accurate description of antimicrobial agents, in contrast to the MIC assay [34]. Based on FICI, Fig.…”

Section: Resultsmentioning

confidence: 99%

Study on Demethoxycurcumin as a promising approach to reverse methicillin-resistance of Staphylococcus aureus

Li¹,

Kang²,

Kwon³

2021

Preprint

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Background Methicillin-resistant Staphylococcus aureus (MRSA) has always been a thorny pathogen, posing serious threat to public health. Current treatment resort for MRSA infections is still scarce. Research on phytochemical component that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigating the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and exploring its possible mechanism for eliminating MRSA resistance. Methods The present study determined minimum inhibitory concentrations (MICs) of DMC, oxacillin, ampicillin and gentamicin against MRSA strains by the broth microdilution method. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time-kill assay. The membrane-permeabilizing agents and ATP synthase inhibitors were employed to explore their impact on the antibacterial ability of DMC. Western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. Results The MIC of DMC against MRSA is 62.5 µg/ml by broth microdilution method. The synergy between DMC and gentamicin was confirmed by checkerboard method and time-kill assay. When ATP synthase inhibitors blocked the metabolic ability of bacteria, the antibacterial effect of DMC was enhanced. The production of penicillin-binding protein 2a (PBP2a) protein and related genes were reduced by DMC at sub-inhibitory concentrations. In addition, DMC hindered the translation of staphylococcal enterotoxin and the transcription of related gene. Conclusions Based on our results, DMC has a significant inhibitory effect on the vitality of MRSA, and it can be inferred that the mechanism by which DMC reverses MRSA resistance is related to the ability of DMC to block resistance determinants (PBP2a and β-lactamase) and S. aureus exotoxin. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

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“…The kill kinetics of antimicrobial activity provides a more accurate description of antimicrobial agents, in contrast to the MIC assay [ 57 ]. In order to determine the synergistic effect from the survival curve of bacteria, the standard strain ATCC 33591 and clinical strain DPS-2 were used to conduct experiments, and three treatment modes (DMC alone, GEN alone and GEN combined with DMC) were designed to compare the antibacterial effects with the control (no drug).…”

Section: Methodsmentioning

confidence: 99%

Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance of Staphylococcus aureus

Kang

Kwon

2021

IJMS

View full text Add to dashboard Cite

Methicillin-resistant Staphylococcus aureus (MRSA) has always been a threatening pathogen. Research on phytochemical components that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigate the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and explore its possible mechanism for eliminating MRSA. The minimum inhibitory concentrations (MICs) of DMC against MRSA strains was determined by the broth microdilution method, and the results showed that the MIC of DMC was 62.5 μg/mL. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time–kill assay. The ATP synthase inhibitors were employed to block the metabolic ability of bacteria to explore their synergistic effect on the antibacterial ability of DMC. In addition, western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. As results, DMC hindered the translation of penicillin-binding protein 2a (PBP2a) and staphylococcal enterotoxin and reduced the transcription of related genes. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

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Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria

Cited by 16 publications

References 30 publications

Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections

Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections

Study on Demethoxycurcumin as a promising approach to reverse methicillin-resistance of Staphylococcus aureus

Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance of Staphylococcus aureus

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