Plumbagin resurrect colistin susceptible against colistin-resistant Pseudomonas aeruginosa in vitro and in vivo

Wang, Yue; Kong, Jingchun; Zhang, Xiaodong; Liu, Yan; Huang, Zeyu; Liu, Yuan; Zhang, Ying; Cao, Jianming; Chen, Lijiang; Liu, Yong; Zhou, Tieli

doi:10.3389/fmicb.2022.1020652

Cited by 15 publications

(15 citation statements)

References 30 publications

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“…Additionally, during the growth of A. fumigatus , the biofilm produced exhibits protective and adhesive properties, leading to increased drug resistance (Di Somma et al, 2020 ). However, previous reports have indicated that PL can inhibit biofilm formation (Qian et al, 2022 ; Wang et al, 2022 ). Therefore, we conducted experiments related to biofilm formation and found that PL significantly inhibited its development.…”

Section: Discussionmentioning

confidence: 92%

“…We conducted experiments on this aspect and discovered that PL effectively inhibited the adhesion of A. fumigatus spores. Previous research has demonstrated that PL can disrupt the structural integrity of bacterial and fungal cell membranes and walls, leading to increased permeability and subsequent cellular demise (Periasamy et al, 2019 ; Shang et al, 2019 ; Qian et al, 2022 ; Wang et al, 2022 ). A similar effect of PL on A. fumigatus keratitis was also confirmed in our study, where the destruction of the cell membrane and cell wall was enhanced in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…The biofilm formation inhibition experiment was slightly modified based on a previous study (Wang et al, 2022 ). In this experiment, 1 × 10 5 CFU/mL of A. fumigatus conidia were co-cultured with different concentrations of PL (0, 3, 6, 8, 10, 20, and 30 μM) or 1‰ DMSO in Sargasparin medium for a duration of 48 h. After fixing the biofilm with methanol, it was stained with crystal violet (0.01%) for 15 min.…”

Section: Methodsmentioning

confidence: 99%

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Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis

Cong,

Gu,

Lin

et al. 2024

Front. Microbiol.

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To investigate the anti-inflammatory and antifungal effects of plumbagin (PL) in Aspergillus fumigatus (A. fumigatus) keratitis, the minimum inhibitory concentration (MIC), time-killing curve, spore adhesion, crystal violet staining, calcium fluoride white staining, and Propidium Iodide (PI) staining were employed to assess the antifungal activity of PL in vitro against A. fumigatus. The cytotoxicity of PL was assessed using the Cell Counting Kit-8 (CCK8). The impact of PL on the expression of HMGB1, LOX-1, TNF-α, IL-1β, IL-6, IL-10 and ROS in A. fumigatus keratitis was investigated using RT-PCR, ELISA, Western blot, and Reactive oxygen species (ROS) assay. The therapeutic efficacy of PL against A. fumigatus keratitis was assessed through clinical scoring, plate counting, Immunofluorescence and Hematoxylin-Eosin (HE) staining. Finally, we found that PL inhibited the growth, spore adhesion, and biofilm formation of A. fumigatus and disrupted the integrity of its cell membrane and cell wall. PL decreased IL-6, TNF-α, and IL-1β levels while increasing IL-10 expression in fungi-infected mice corneas and peritoneal macrophages. Additionally, PL significantly attenuated the HMGB1/LOX-1 pathway while reversing the promoting effect of Boxb (an HMGB1 agonist) on HMGB1/LOX-1. Moreover, PL decreased the level of ROS. In vivo, clinical scores, neutrophil recruitment, and fungal burden were all significantly reduced in infected corneas treated with PL. In summary, the inflammatory process can be inhibited by PL through the regulation of the HMGB-1/LOX-1 pathway. Simultaneously, PL can exert antifungal effects by limiting fungal spore adhesion and biofilm formation, as well as causing destruction of cell membranes and walls.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis

Cong,

Gu,

Lin

et al. 2024

Front. Microbiol.

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“…Currently, the use of antibacterial drug adjuvants that restore sensitivity of MDR pathogens to antibiotics, or “rejuvenation”, has attracted the attention of many researchers. A combination of nontraditional antibiotics and colistin generated a synergistic effect against COL-R Gram-negative bacteria, − indicating that “antibiotic recycling” can be achieved when the combination is used to treat COL-R infections, owing to reduced amounts of colistin used . Therefore, the combination of adjuvants and antibiotics to overcome bacterial resistance in new therapeutic strategies has clinical application.…”

Section: Discussionmentioning

confidence: 99%

Azomycin Orchestrate Colistin-Resistant Enterobacter cloacae Complex’s Colistin Resistance Reversal In Vitro and In Vivo

Hu,

Chen,

Zhao

et al. 2024

ACS Infect. Dis.

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The Enterobacter cloacae complex (ECC) is a group of nosocomial pathogens that pose a challenge in clinical treatment due to its intrinsic resistance and the ability to rapidly acquire resistance. Colistin was reconsidered as a last-resort antibiotic for combating multidrug-resistant ECC. However, the persistent emergence of colistin-resistant (COL-R) pathogens impedes its clinical efficacy, and novel treatment options are urgently needed. We propose that azomycin, in combination with colistin, restores the susceptibility of COL-R ECC to colistin in vivo and in vitro. Results from the checkerboard susceptibility, time-killing, and live/dead bacterial cell viability tests showed strong synergistic antibacterial activity in vitro. Animal infection models suggested that azomycin−colistin enhanced the survival rate of infected Galleria mellonella and reduced the bacterial load in the thighs of infected mice, highlighting its superior in vivo synergistic antibacterial activity. Crystal violet staining and scanning electron microscopy unveiled the in vitro synergistic antibiofilm effects of azomycin−colistin. The safety of azomycin and azomycin−colistin at experimental concentrations was confirmed through cytotoxicity tests and an erythrocyte hemolysis test. Azomycin−colistin stimulated the production of reactive oxygen species in COL-R ECC and inhibited the PhoPQ two-component system to combat bacterial growth. Thus, azomycin is feasible as a colistin adjuvant against COL-R ECC infection.

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“…After 0, 1, 2, 4, 6, 8 and 24 h incubation, an aliquot was taken from each sample and diluted in PBS. Serial 10-fold dilutions of the broth cultures were plated on LB agar and incubated at 37 • C for 24 h. The synergistic effect was defined as a reduction of 2 log 10 CFU/mL [33].…”

Section: Time-kill Assaysmentioning

confidence: 99%

PYED-1 Overcomes Colistin Resistance in Acinetobacter baumannii

Stabile,

Esposito,

Iula

et al. 2023

Pathogens

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Antibiotic resistance has become more and more widespread over the recent decades, becoming a major global health problem and causing colistin to be increasingly used as an antibiotic of last resort. Acinetobacter baumannii, an opportunistic pathogen that has rapidly evolved into a superbug exhibiting multidrug-resistant phenotypes, is responsible for a large number of hospital infection outbreaks. With the intensive use of colistin, A. baumannii resistance to colistin has been found to increase significantly. In previous work, we identified a deflazacort derivative, PYED-1 (pregnadiene-11-hydroxy-16,17-epoxy-3,20-dione-1), which exhibits either direct-acting or synergistic activity against Gram-positive and Gram-negative species and Candida spp., including A. baumannii. The aim of this study was to evaluate the antibacterial activity of PYED-1 in combination with colistin against both A. baumannii planktonic and sessile cells. Furthermore, the cytotoxicity of PYED-1 with and without colistin was assessed. Our results show that PYED-1 and colistin can act synergistically to produce a strong antimicrobial effect against multidrug-resistant populations of A. baumannii. Interestingly, our data reveal that PYED-1 is able to restore the efficacy of colistin against all colistin-resistant A. baumannii isolates. This drug combination could achieve a much stronger antimicrobial effect than colistin while using a much smaller dosage of the drugs, additionally eliminating the toxicity and resistance issues associated with the use of colistin.

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Plumbagin resurrect colistin susceptible against colistin-resistant Pseudomonas aeruginosa in vitro and in vivo

Cited by 15 publications

References 30 publications

Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis

Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis

Azomycin Orchestrate Colistin-Resistant Enterobacter cloacae Complex’s Colistin Resistance Reversal In Vitro and In Vivo

PYED-1 Overcomes Colistin Resistance in Acinetobacter baumannii

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