Antimicrobial resistance in Rhodococcus equi.

Cisek, Agata Anna; Rzewuska, Magdalena; Witkowski, Lucjan; Binek, M.

doi:10.18388/abp.2014_1824

Cited by 22 publications

(10 citation statements)

References 42 publications

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“…Antioxidants 2020, 9,114 4 of 10 redox potential of this biosensor was established recently as −290 mV [17], whereas the EroGFP2 of Mrx1-roGFP2 in response to 5 mM H2O2 was −264 mV and the intracellular redox potential during host cell infection was −260 mV. Overall, these results confirmed that rifampicin, erythromycin, and vancomycin elicited a significant oxidative stress as part of their mechanism of action.…”

Section: Resultssupporting

confidence: 72%

“…Antioxidants 2020, 9,114 6 of 10 commonly used combination of erythromycin and rifampicin (Figure 3). Interestingly, norfloxacin combined with either rifampicin, erythromycin, or vancomycin had an equivalent antimicrobial effect to the antibiotherapy based on erythromycin and rifampicin (Figure 3).…”

Section: Combinatorial Antibiotherapy Against R Equi With Ros-generamentioning

confidence: 99%

“…During the last decade, the number of R. equi isolates resistant to commonly used antimicrobials has dramatically increased [7][8][9], making current antibiotherapies often ineffective [10]. Primary preventative strategies based on the use of vaccines or hyperimmune plasma administration do not confer full protection against this pathogen [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi

Mourenza¹,

Gil²,

Mateos³

et al. 2020

Antioxidants

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: Rhodococcus equi is a facultative intracellular pathogen that causes infections in foals and many other animals such as pigs, cattle, sheep, and goats. Antibiotic resistance is rapidly rising in horse farms, which makes ineffective current antibiotic treatments based on a combination of macrolides and rifampicin. Therefore, new therapeutic strategies are urgently needed to treat R. equi infections caused by antimicrobial resistant strains. Here, we employed a R. equi mycoredoxin-null mutant strain highly susceptible to oxidative stress to screen for novel ROS-generating antibiotics. Then, we used the well-characterized Mrx1-roGFP2 biosensor to confirm the redox stress generated by the most promising antimicrobial agents identified in our screening. Our results suggest that different combinations of antibacterial compounds that elicit oxidative stress are promising anti-infective strategies against R. equi. In particular, the combination of macrolides with ROS-generating antimicrobial compounds such as norfloxacin act synergistically to produce a potent antibacterial effect against R. equi. Therefore, our screening approach could be applied to identify novel ROS-inspired therapeutic strategies against intracellular pathogens.

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Section: Resultssupporting

confidence: 72%

Section: Combinatorial Antibiotherapy Against R Equi With Ros-generamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi

Mourenza¹,

Gil²,

Mateos³

et al. 2020

Antioxidants

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“…Human patients with normal renal function should receive a loading dosage of 25–30 mg of vancomycin per kg intravenously over 1 h, followed by a regular dose every 12 h [ 26 , 27 ]. However, the practical dosing intervals can be 8, 12, 24, and 48 h based on the creatinine clearance of the patient [ 28 ].…”

Section: Therapeutic Indications Of Vancomycinmentioning

confidence: 99%

Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy, Prevention of Resistance and Alternative Therapy

Wijesekara

Kumbukgolla

Jayaweera

et al. 2017

Veterinary Sciences

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Vancomycin is one of the “last-line” classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in the 1950s, it was widely used after the 1980s for the treatment of infections caused by methicillin-resistant Staphylococci, as the prevalence of these strains were increased. However, it is currently evident that vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci have developed for various reasons, including the use of avaparcin—an analog of vancomycin—as a feed additive in livestock. Therefore, prophylactic and empiric use of antibiotics and their analogues need to be minimized. Herein we discuss the rational use of vancomycin in treating humans, horses, farm animals, and pet animals such as dogs, cats, and rabbits. In present day context, more attention should be paid to the prevention of the emergence of resistance to antibiotics in order to maintain their efficacy. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have an in-depth understanding of the antibiotic that they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discuss the pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects, and alternative therapy for vancomycin.

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“…This facultative intracellular pathogen is transmitted by inhaling contaminated soil dust or respiratory particles produced by infected animals [6,7]. Current treatments are based on a combination of macrolides and rifampicin; however, they are becoming ineffective due to the spread of antibiotic resistance [8,9,10,11].…”

Section: Introductionmentioning

confidence: 99%

Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi

et al. 2019

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Rhodococcus equi is a facultative intracellular pathogen that can survive within macrophages of a wide variety of hosts, including immunosuppressed humans. Current antibiotherapy is often ineffective, and novel therapeutic strategies are urgently needed to tackle infections caused by this pathogen. In this study, we identified three mycoredoxin-encoding genes (mrx) in the genome of R. equi, and we investigated their role in virulence. Importantly, the intracellular survival of a triple mrx-null mutant (Δmrx1Δmrx2Δmrx3) in murine macrophages was fully impaired. However, each mycoredoxin alone could restore the intracellular proliferation rate of R. equi Δmrx1Δmrx2Δmrx3 to wild type levels, suggesting that these proteins could have overlapping functions during host cell infection. Experiments with the reduction-oxidation sensitive green fluorescent protein 2 (roGFP2) biosensor confirmed that R. equi was exposed to redox stress during phagocytosis, and mycoredoxins were involved in preserving the redox homeostasis of the pathogen. Thus, we studied the importance of each mycoredoxin for the resistance of R. equi to different oxidative stressors. Interestingly, all mrx genes did have overlapping roles in the resistance to sodium hypochlorite. In contrast, only mrx1 was essential for the survival against high concentrations of nitric oxide, while mrx3 was not required for the resistance to hydrogen peroxide. Our results suggest that all mycoredoxins have important roles in redox homeostasis, contributing to the pathogenesis of R. equi and, therefore, these proteins may be considered interesting targets for the development of new anti-infectives.

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Antimicrobial resistance in Rhodococcus equi.

Cited by 22 publications

References 42 publications

A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi

A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi

Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy, Prevention of Resistance and Alternative Therapy

Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi

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