Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

Rafailidis, Petros; Panagopoulos, Periklis; Koutserimpas, Christos; Samonis, George

doi:10.3390/antibiotics13030261

Cited by 5 publications

(1 citation statement)

References 129 publications

(179 reference statements)

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“…Among them, we focused on the increased susceptibility to minocycline and tigecycline in the Δ phoQ mutant (red bars). Although minocycline and tigecycline are potent antibiotics in treating infections caused by multidrug-resistant Gram-negative pathogens (20, 21), their mechanisms of resistance remains poorly understood, which prompted us to elucidate the underlying mechanisms of these phenotypes.…”

Section: Resultsmentioning

confidence: 99%

PhoPQ-mediated lipopolysaccharide modification regulates intrinsic resistance to tetracycline and glycylcycline antibiotics inEscherichia coli

Choi,

Ryu

et al. 2024

Preprint

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Tetracyclines and glycylcycline are among the last-resort antibiotics used to combat infections caused by multidrug-resistant Gram-negative pathogens. Despite the clinical importance of these antibiotics, their mechanisms of resistance remain unclear. In this study, we elucidated a novel mechanism of resistance to tetracycline and glycylcycline antibiotics via lipopolysaccharide (LPS) modification. Disruption of theEscherichia coliPhoPQ two-component system, which regulates the transcription of various genes involved in magnesium transport and LPS modification, leads to increased susceptibility to tetracycline, minocycline, doxycycline, and tigecycline. These phenotypes are caused by enhanced expression of phosphoethanolamine transferase EptB, which catalyzes the modification of the inner core sugar of LPS. PhoPQ-mediated regulation of EptB expression appears to affect the intracellular transportation of doxycycline. Disruption of EptB increases resistance to tetracycline and glycylcycline antibiotics, whereas the other two phosphoethanolamine transferases, EptA and EptC, that participate in the modification of other LPS residues, are not associated with resistance to tetracyclines and glycylcycline. Overall, our results demonstrated that PhoPQ-mediated modification of a specific residue of LPS by phosphoethanolamine transferase EptB regulates resistance to tetracycline and glycylcycline antibiotics.ImportanceElucidating the resistance mechanisms of clinically important antibiotics helps in maintaining the clinical efficacy of antibiotics and in the prescription of adequate antibiotic therapy. Although tetracycline and glycylcycline antibiotics are clinically important in combating multidrug-resistant Gram-negative bacterial infections, their mechanisms of resistance are not fully understood. Our research demonstrates that theEscherichia colitwo-component system PhoPQ regulates resistance to tetracycline and glycylcycline antibiotics by controlling the expression of phosphoethanolamine transferase EptB, which catalyzes the modification of the inner core residue of lipopolysaccharide (LPS). Therefore, our findings highlight a novel resistance mechanism to tetracycline and glycylcycline antibiotics and the physiological significance of LPS core modification inE. coli.One sentence summaryLipopolysaccharide modification-mediated tigecycline resistance

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Section: Resultsmentioning

confidence: 99%

PhoPQ-mediated lipopolysaccharide modification regulates intrinsic resistance to tetracycline and glycylcycline antibiotics inEscherichia coli

Choi,

Ryu

et al. 2024

Preprint

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Exploring bacterial extracellular vesicles: Focus on WHO critical priority pathogens

Rocha Minarini

2024

Current Topics in Membranes

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Third-Generation Tetracyclines: Current Knowledge and Therapeutic Potential

Kounatidis,

Dalamaga,

Grivakou

et al. 2024

Biomolecules

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Tetracyclines constitute a unique class of antibiotic agents, widely prescribed for both community and hospital infections due to their broad spectrum of activity. Acting by disrupting protein synthesis through tight binding to the 30S ribosomal subunit, their interference is typically reversible, rendering them bacteriostatic in action. Resistance to tetracyclines has primarily been associated with changes in pump efflux or ribosomal protection mechanisms. To address this challenge, tetracycline molecules have been chemically modified, resulting in the development of third-generation tetracyclines. These novel tetracyclines offer significant advantages in treating infections, whether used alone or in combination therapies, especially in hospital settings. Beyond their conventional antimicrobial properties, research has highlighted their potential non-antibiotic properties, including their impact on immunomodulation and malignancy. This review will focus on third-generation tetracyclines, namely tigecycline, eravacycline, and omadacycline. We will delve into their mechanisms of action and resistance, while also evaluating their pros and cons over time. Additionally, we will explore their therapeutic potential, analyzing their primary indications of prescription, potential future uses, and non-antibiotic features. This review aims to provide valuable insights into the clinical applications of third-generation tetracyclines, thereby enhancing understanding and guiding optimal clinical use.

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Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

Cited by 5 publications

References 129 publications

PhoPQ-mediated lipopolysaccharide modification regulates intrinsic resistance to tetracycline and glycylcycline antibiotics inEscherichia coli

PhoPQ-mediated lipopolysaccharide modification regulates intrinsic resistance to tetracycline and glycylcycline antibiotics inEscherichia coli

Exploring bacterial extracellular vesicles: Focus on WHO critical priority pathogens

Third-Generation Tetracyclines: Current Knowledge and Therapeutic Potential

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