Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli

Zhong, Zhaoyang; Cui, Ze-Hua; Li, Xiaojie; Tang, Tian; Zheng, Zi-Jian; Ni, Wei-Na; Fang, Liang‐Xing; Zhou, Yufeng; Yu, Yang; Liao, Xiao‐Ping; Sun, Jian

doi:10.3389/fcimb.2020.608547

Cited by 15 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Time–kill experiments were conducted to further characterize the synergistic activity of the phentolamine and macrolide combinations as previously described [ 15 ]. In brief, ~10 6 colony-forming units (CFU)/mL of logarithmic phase cells were incubated with erythromycin in the presence and absence of phentolamine.…”

Section: Methodsmentioning

confidence: 99%

“…The G. mellonella model system was used to assess in vivo antibiotic functions, as we previously reported [ 15 ]. In brief, G. mellonella larvae were obtained from Kaide Ruixin (Tianjin, China), and the optimal infective dose was determined using 250 mg cream-colored larvae that we randomly distributed into six experimental groups (n = 10/group).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Cui

Zheng

et al. 2023

Antibiotics

Self Cite

View full text Add to dashboard Cite

Objectives: Multidrug-resistant (MDR) Gram-negative bacterial infections have limited treatment options due to the impermeability of the outer membrane. New therapeutic strategies or agents are urgently needed, and combination therapies using existing antibiotics are a potentially effective means to treat these infections. In this study, we examined whether phentolamine can enhance the antibacterial activity of macrolide antibiotics against Gram-negative bacteria and investigated its mechanism of action. Methods: Synergistic effects between phentolamine and macrolide antibiotics were evaluated by checkerboard and time–kill assays and in vivo using a Galleria mellonella infection model. We utilized a combination of biochemical tests (outer membrane permeability, ATP synthesis, ΔpH gradient measurements, and EtBr accumulation assays) with scanning electron microscopy to clarify the mechanism of phentolamine enhancement of macrolide antibacterial activity against Escherichia coli. Results: In vitro tests of phentolamine combined with the macrolide antibiotics erythromycin, clarithromycin, and azithromycin indicated a synergistic action against E. coli test strains. The fractional concentration inhibitory indices (FICI) of 0.375 and 0.5 indicated a synergic effect that was consistent with kinetic time–kill assays. This synergy was also seen for Salmonella typhimurium, Klebsiella pneumoniae, and Actinobacter baumannii but not Pseudomonas aeruginosa. Similarly, a phentolamine/erythromycin combination displayed significant synergistic effects in vivo in the G. mellonella model. Phentolamine added singly to bacterial cells also resulted in direct outer membrane damage and was able to dissipate and uncouple membrane proton motive force from ATP synthesis that, resulted in enhanced cytoplasmic antibiotic accumulation via reduced efflux pump activity. Conclusions: Phentolamine potentiates macrolide antibiotic activity via reducing efflux pump activity and direct damage to the outer membrane leaflet of Gram-negative bacteria both in vitro and in vivo.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Cui

Zheng

et al. 2023

Antibiotics

Self Cite

View full text Add to dashboard Cite

show abstract

“…After incubation at 37°C for 18 hours, the MIC values were defined as the lowest concentrations of antibiotics with no visible growth of bacteria. For better understanding the synergy between colistin and selected phytochemicals, the checkerboard assay was conducted to determine the FICI as described previously with minor modifications ( 67 ). In brief, 100 μl of LPM broth was first dispensed to each well in a microtiter plate with serial diluted colistin and selected phytochemicals.…”

Section: Methodsmentioning

confidence: 99%

“…The bacteria were cultured to exponential phase and then diluted in LPM to ~10 6 CFU/ml, which were subsequently treated with subinhibitory concentrations of colistin, the selected flavonoids (25 mg/liter), or their combination. At time points 0, 3, 6, 9, and 24 hours, a 100-μl aliquot of each treatment was removed, diluted, and plated to determine bacterial survivors ( 67 ).…”

Section: Methodsmentioning

confidence: 99%

Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy

et al. 2023

Self Cite

View full text Add to dashboard Cite

In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids—7,8-dihydroxyflavone, myricetin, and luteolin—prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system pmrA / pmrB , thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.

show abstract

“…UTIs result in compromised socioeconomical factors and health, affecting the quality life of affected individuals [20]. Currently, medications used for UTIs include trimethoprim sulfamethoxazole, ciprofloxacin, ampicillin [21], and combined antibiotic therapy to address the multidrugresistance (MDR) features of virulent bacteria [22]. Vaccines targeting bacterial adhesions and bacterial toxins are also available [23,24].…”

Section: Introductionmentioning

confidence: 99%

Nanomaterials for the Diagnosis and Treatment of Urinary Tract Infections

et al. 2021

View full text Add to dashboard Cite

The diagnosis and treatment of urinary tract infections (UTIs) remain challenging due to the lack of convenient assessment techniques and to the resistance to conventional antimicrobial therapy, showing the need for novel approaches to address such problems. In this regard, nanotechnology has a strong potential for both the diagnosis and therapy of UTIs via controlled delivery of antimicrobials upon stable, effective and sustained drug release. On one side, nanoscience allowed the production of various nanomaterial-based evaluation tools as precise, effective, and rapid procedures for the identification of UTIs. On the other side, nanotechnology brought tremendous breakthroughs for the treatment of UTIs based on the use of metallic nanoparticles (NPs) for instance, owing to the antimicrobial properties of metals, or of surface-tailored nanocarriers, allowing to overcome multidrug-resistance and prevent biofilm formation via targeted drug delivery to desired sites of action and preventing the development of cytotoxic processes in healthy cells. The goal of the current study is therefore to present the newest developments for the diagnosis and treatment of UTIs based on nanotechnology procedures in relation to the currently available techniques.

show abstract

Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli

Cited by 15 publications

References 55 publications

Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy

Nanomaterials for the Diagnosis and Treatment of Urinary Tract Infections

Contact Info

Product

Resources

About