Resistance and Tolerance to Aminoglycosides

Mok, Wendy W. K.; Brynildsen, Mark P.

doi:10.1002/9781119593522.ch4

Cited by 2 publications

(1 citation statement)

References 93 publications

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“…In June 2018, plazomicin was approved by the US Food and Drug Administration (FDA) for treatment of complicated urinary tract infections, including acute pyelonephritis [12] and is waiting for FDA approval for acute bloodstream infections caused by MDR Enterobacteriaceae infections, including CRE [13].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Activity of Plazomicin among Carbapenem-resistant Enterobacteriaceae

Essam

Nawar

ElBashaar

et al. 2021

Open Access Maced J Med Sci

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Background: Carbapenem-resistant Enterobacteriaceae (CRE) have been disseminated worldwide and became a global threat. Due to limited therapeutic drugs plazomicin - a new semisynthetic aminoglycoside - have been suggested as an alternative option owing to its stability against aminoglycosides modifying enzymes (AMEs). This study aims to assess the in vitro activity of plazomicin against CRE isolates and to detect different types of carbapenemases among these isolates. Material and Methods: In this study, 102 CRE isolates were collected from different clinical samples at Cairo University hospitals and the presence of carbapenemases was detected by modified carbapenem inhibition method (mCIM) and multiplex PCR tests. Plazomicin susceptibility testing was done using E test. Results: The most frequently detected carbapenemase genes were blaNDM in 75 (73.5%) isolates, followed by blaOXA-48 in 57 (55.9%) and blaKPC in 16 (15.5%) isolates. Plazomicin was active against 32 (31.4%) isolates. Among the isolates carrying blaNDM gene only and those carrying blaOXA-48 gene only, 21% and 41% were sensitive to plazomicin, respectively. Plazomicin showed the highest sensitivity against CRE isolates compared to the other tested antibiotics. Conclusion: Plazomicin might be a good option for treatment of infections caused by CRE. In health care settings where blaNDM gene is prevalent, plazomicin may not be a good therapeutic option for CRE infections.

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Section: Introductionmentioning

confidence: 99%

In Vitro Activity of Plazomicin among Carbapenem-resistant Enterobacteriaceae

Essam

Nawar

ElBashaar

et al. 2021

Open Access Maced J Med Sci

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Improved Growth of Escherichia coli in Aminoglycoside Antibiotics by the zor-orz Toxin-Antitoxin System

et al. 2022

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Type I toxin-antitoxin systems consist of a small protein (under 60 amino acids) whose overproduction can result in cell growth stasis or death, and a small RNA that represses translation of the toxin mRNA. Despite their potential toxicity, type I toxin proteins are increasingly linked to improved survival of bacteria in stressful environments and antibiotic persistence. While the interaction of toxin mRNAs with their cognate antitoxin sRNAs in some systems are well characterized, additional translational control of many toxins and their biological roles are not well understood. Using an ectopic overexpression system, we show that the efficient translation of a chromosomally encoded type I toxin, ZorO, requires mRNA processing of its long 5’ untranslated region (UTR; Δ28 UTR). The severity of ZorO induced toxicity on growth inhibition, membrane depolarization, and ATP depletion were significantly increased if expressed from the Δ28 UTR versus the full-length UTR. ZorO did not form large pores as evident via a liposomal leakage assay, in vivo morphological analyses, and measurement of ATP loss. Further, increasing the copy number of the entire zor-orz locus significantly improved growth of bacterial cells in the presence of kanamycin and increased the minimum inhibitory concentration against kanamycin and gentamycin; however, no such benefit was observed against other antibiotics. This supports a role for the zor-orz locus as a protective measure against specific stress agents and is likely not part of a general stress response mechanism. Combined, these data shed more insights into the possible native functions for type I toxin proteins. IMPORTANCE Bacterial species can harbor gene pairs known as type I toxin-antitoxin systems where one gene encodes a small protein that is toxic to the bacteria producing it and a second gene that encodes a small RNA antitoxin to prevent toxicity. While artificial overproduction of type I toxin proteins can lead to cell growth inhibition and cell lysis, the endogenous translation of type I toxins appears to be tightly regulated. Here, we show translational regulation controls production of the ZorO type I toxin and prevents subsequent negative effects on the cell. Further, we demonstrate a role for zorO and its cognate antitoxin in improved growth of E. coli in the presence of aminoglycoside antibiotics.

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Resistance and Tolerance to Aminoglycosides

Cited by 2 publications

References 93 publications

In Vitro Activity of Plazomicin among Carbapenem-resistant Enterobacteriaceae

In Vitro Activity of Plazomicin among Carbapenem-resistant Enterobacteriaceae

Improved Growth of Escherichia coli in Aminoglycoside Antibiotics by the zor-orz Toxin-Antitoxin System

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