4F-Indole Enhances the Susceptibility of Pseudomonas aeruginosa to Aminoglycoside Antibiotics

Dou, Qin; Zhu, Yuxiang; Li, Chunhui; Bian, Zeran; Song, Huihui; Zhang, Ruizhen; Wang, Yingsong; Zhang, Xile; Wang, Yan

doi:10.1128/spectrum.04519-22

Cited by 7 publications

(4 citation statements)

References 54 publications

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“…This situation coincided with the national trend, as there was an increase in the percentage of resistant strains in Poland after 2012, which finally reached about 37% in 2018 [27,33]. As of 2019, on the other hand, a decrease in the resistance of these bacteria to piperacillin with tazobactam was observed, shaping up at 20%, both in the hospital studied and nationally, thus approaching the global average of about 13% [26,32]. In the studied hospital, the use of antibiotics with inhibitors has increased significantly in recent years, but this mainly involves amoxicillin with clavulanate (which is inactive against Pseudomonas) and results in a decrease in its activity against many hospital pathogens.…”

Section: Discussionmentioning

confidence: 55%

“…These data show that the buildup of carbapenem resistance in P. aeruginosa after the pandemic shows a lower rate than that of CPE (carbapenem-resistant Enterobacterales). In addition to resistance to β-lactam antibiotics, P. aeruginosa have also developed resistance to aminoglycosides [31,32]. In many countries in Europe, as well as worldwide, there has been a decline in the percentage of Pseudomonas strains resistant to aminoglycosides after 2009.…”

Section: Discussionmentioning

confidence: 99%

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Changes in Antibiotic Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Clinical Isolates in a Multi-Profile Hospital in Years 2017–2022 in Wroclaw, Poland

Mączyńska,

Jama-Kmiecik,

Sarowska

et al. 2023

JCM

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In recent years, we have witnessed increasing drug resistance among bacteria, which is associated with the use and availability of an increasing number of broad-spectrum antimicrobials, as well as with their irrational and excessive use. The present study aims to analyze changes in the drug resistance of Gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from infections in a multi-profile hospital over a five-year period (from 2017 to 2022). Among the practical results of the evaluation of these data will be the possibility to determine changes in susceptibility to the antibiotics used in the hospital. This, in turn, will help propose new therapeutic options, especially for empirical therapy, which is essential in severe infections. Analysis of the use of different antibiotic groups has made it possible to identify the causes of increasing resistance in the analyzed Gram-negative bacilli. The highest antibiotic use was observed in the hospital between 2020 and 2022, most probably due to the COVID-19 pandemic and the higher number of patients in severe condition requiring hospitalization. Unfortunately, during the period analyzed, the number of multi-resistant strains of A. baumannii was successively increasing; this seems to be related to the increased use, especially during the pandemic period, of broad-spectrum antibiotics, mainly penicillins with inhibitors, third-generation cephalosporins and carbapenems.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Changes in Antibiotic Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Clinical Isolates in a Multi-Profile Hospital in Years 2017–2022 in Wroclaw, Poland

Mączyńska,

Jama-Kmiecik,

Sarowska

et al. 2023

JCM

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“…Recently, another class of efflux pump inhibitors, namely halogenated indoles, was synthesized and the representative molecule, 4F-indole, was characterized as a possible MexXY-OprM inhibitor. This molecule showed an aminoglycoside-enhancing effect, similar to berberine derivatives, but with a different mechanism of action that relied on indirect inhibition of the efflux pump, through the activation of the PmrAB two-component system [134].…”

Section: Efflux Pump Inhibitorsmentioning

confidence: 98%

New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis

Scoffone,

Barbieri,

Irudal

et al. 2024

Antibiotics

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People with cystic fibrosis (CF) suffer from recurrent bacterial infections which induce inflammation, lung tissue damage and failure of the respiratory system. Prolonged exposure to combinatorial antibiotic therapies triggers the appearance of multi-drug resistant (MDR) bacteria. The development of alternative antimicrobial strategies may provide a way to mitigate antimicrobial resistance. Here we discuss different alternative approaches to the use of classic antibiotics: anti-virulence and anti-biofilm compounds which exert a low selective pressure; phage therapies that represent an alternative strategy with a high therapeutic potential; new methods helping antibiotics activity such as adjuvants; and antimicrobial peptides and nanoparticle formulations. Their mechanisms and in vitro and in vivo efficacy are described, in order to figure out a complete landscape of new alternative approaches to fight MDR Gram-negative CF pathogens.

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“…ArmZ physically interacts with MexZ to reduce the binding ability of MexZ to target DNA, leading to the overexpression of the mexXY operon (Hay et al., 2013 ; Kawalek et al., 2019 ; Morita, Sobel Mara, & Poole, 2006 ; Yamamoto et al., 2009 ). Transcriptional expression of armZ is repressed by the TCS PmrA/PmrB which is activated by halogenated indoles (Dou et al., 2023 ). In addition, polynucleotide phosphorylase (PNPase) was found to control the translation of the armZ mRNA through its 5′ UTR (Fan et al., 2021 ).…”

Section: Efflux Pumps In P Aeruginosamentioning

confidence: 99%

Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications

Wu,

Huang,

2024

Microbial Biotechnology

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Pseudomonas aeruginosa is a notorious multidrug‐resistant pathogen that poses a serious and growing threat to the worldwide public health. The expression of resistance determinants is exquisitely modulated by the abundant regulatory proteins and the intricate signal sensing and transduction systems in this pathogen. Downregulation of antibiotic influx porin proteins and upregulation of antibiotic efflux pump systems owing to mutational changes in their regulators or the presence of distinct inducing molecular signals represent two of the most efficient mechanisms that restrict intracellular antibiotic accumulation and enable P. aeruginosa to resist multiple antibiotics. Treatment of P. aeruginosa infections is extremely challenging due to the highly inducible mechanism of antibiotic resistance. This review comprehensively summarizes the regulatory networks of the major porin proteins (OprD and OprH) and efflux pumps (MexAB‐OprM, MexCD‐OprJ, MexEF‐OprN, and MexXY) that play critical roles in antibiotic influx and efflux in P. aeruginosa. It also discusses promising therapeutic approaches using safe and efficient adjuvants to enhance the efficacy of conventional antibiotics to combat multidrug‐resistant P. aeruginosa by controlling the expression levels of porins and efflux pumps. This review not only highlights the complexity of the regulatory network that induces antibiotic resistance in P. aeruginosa but also provides important therapeutic implications in targeting the inducible mechanism of resistance.

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4F-Indole Enhances the Susceptibility of Pseudomonas aeruginosa to Aminoglycoside Antibiotics

Cited by 7 publications

References 54 publications

Changes in Antibiotic Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Clinical Isolates in a Multi-Profile Hospital in Years 2017–2022 in Wroclaw, Poland

Changes in Antibiotic Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Clinical Isolates in a Multi-Profile Hospital in Years 2017–2022 in Wroclaw, Poland

New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis

Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications

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