Pixantrone Sensitizes Gram-Negative Pathogens to Rifampin

She, Pengfei; Li, Zehao; Li, Yimin; Li, Shasha; Li, Linhui; Yang, Yifan; Zhou, Linying; Wu, Yong

doi:10.1128/spectrum.02114-22

Cited by 6 publications

(5 citation statements)

References 68 publications

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“…The fractional inhibitory concentration index (FICI) was calculated using the following formula: (MIC of B in combination)/(MIC of B alone) + (MIC of antibiotic in combination)/(MIC of antibiotic alone). The FICI values were interpreted as follows: FICI ≤0.5 indicate synergy, 0.5 < FICI <4 indicate indifference, while values >4 indicate antagonism ( She et al, 2022 ). Three independent biological replicates were performed.…”

Section: Methodsmentioning

confidence: 99%

Anti-staphylococcal activity of a polyphenol-rich citrus extract: synergy with β-lactams and low proficiency to induce resistance

Mazzantini,

Massimino,

Calvigioni

et al. 2024

Front. Microbiol.

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IntroductionAntibiotic resistance represents one of the most significant threats to public health in the 21st century. Polyphenols, natural molecules with antibacterial activity produced by plants, are being considered as alternative antimicrobial strategies to manage infections caused by drug-resistant bacteria. In this study, we investigated the antibacterial activity of a polyphenol mixture extracted from citrus fruits, against both antibiotic-susceptible and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis.MethodsBroth microdilution and time-kill curve experiments were used to test the extract anti-staphylococcal activity. Cytotoxicity was assessed by the hemolysis assay. The interaction between the mixture and antibiotics was investigated by the checkerboard assay. The effect of B alone and in combination with oxacillin on the membrane potential was investigated by the 3,3′-dipropylthiadicarbocyanine iodide assay. The ability of the extract to induce the development of resistance was verified by propagating S. aureus for 10 transfers in the presence of sub-inhibitory concentrations.ResultsThe citrus extract was found to be active against all Staphylococcus strains at remarkably low concentrations (0.0031 and 0.0063%), displaying rapid bactericidal effects without being toxic on erythrocytes. In particular, B was found to rapidly cause membrane depolarization. When combined with methicillin, meropenem, and oxacillin, the mixture displayed synergistic activity exclusively against methicillin-resistant strains. We additionally show that the sequential exposure of S. aureus to sub-inhibitory concentrations did not induce the development of resistance against the extract.DiscussionOverall, these findings support the potential use of the citrus extract as promising option to manage staphylococcal infections and suggest that it may counteract the mechanism behind methicillin-resistance.

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Section: Methodsmentioning

confidence: 99%

Anti-staphylococcal activity of a polyphenol-rich citrus extract: synergy with β-lactams and low proficiency to induce resistance

Mazzantini,

Massimino,

Calvigioni

et al. 2024

Front. Microbiol.

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“…LIVE/DEAD BacLight bacterial viability kits (Molecular Probes) containing SYTO9 and PI were used to distinguish between live and dead bacteria. The samples were visualized using a Zeiss Axio Scope A1 upright microscope, and the images were processed for merging using the ImageJ software ( 46 ).…”

Section: Methodsmentioning

confidence: 99%

“…Next, the bacterial suspensions were mixed with 10 nmol/L of PI (Solarbio, Beijing, China) to detect the permeabilization of the inner membrane, and then the suspensions were coincubated for 30 min in the dark. The fluorescence was detected at emission/excitation wavelengths of 615/535 nm ( 46 ). In the fluorescence or luminescence assay, the corresponding concentrations of drugs (without cells) were incubated with probes as blank controls, and the relative fluorescence intensity was calculated as the value of the analyte minus the value of the blank control.…”

Section: Methodsmentioning

confidence: 99%

“…Bacterial suspension with an OD 600 of 0.5 was coincubated with 0.2 × 10 −6 M of 2’,7’-Bis (2-carboxyethyl-5(6)-carboxyfluorescein) (BCECF)-AM (acetoxymethyl ester) or 0.5 × 10 −3 mM of 3,3-dipropylthiadicarbocyanine iodide [DiSC 3 (5); Sigma-Aldrich] for 30 min at 37°C. Then, 10 μL of different drugs, glucose (2.5 × 10 −5 M), or melittin (16 μg/mL) was added as a supplement and incubated for 30 min, and the fluorescence values of PMF and dissipated bacterial ΔΨ were determined by excitation/emission at 500/522 nm and 622/670 nm, respectively ( 46 ).…”

Section: Methodsmentioning

confidence: 99%

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Baicalein Resensitizes Multidrug-Resistant Gram-Negative Pathogens to Doxycycline

Wang

Zhou

et al. 2023

Microbiol Spectr

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“…After incubation at 37℃ for 16-18 h, the optical density at 630 nm (OD 630 ) was measured, and the antibacterial interaction between the drugs was calculated by . FICI ≤ 0.5 indicates synergy, 0.5 < FICI ≤ 4 indicates no interaction, and FICI > 4 indicates antagonism (She et al 2022).…”

Section: Checkerboard Assaymentioning

confidence: 99%

Simeprevir restores the anti-Staphylococcus activity of polymyxins

Wu,

et al. 2023

AMB Expr

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Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities against Staphylococcus aureus (S. aureus). However, the combination of antibiotics with antibiotic adjuvants is a feasible strategy for the hard-treated infection and toxicity reducing. We will investigate the antibacterial activity of simeprevir (SIM), which treated for genotype 1 and 4 chronic hepatitis C, combined with polymyxins against MRSA through high-throughput screening technology. In our study, the synergistic antibacterial effect of SIM and polymyxins against S. aureus in vitro was found by checkerboard assay and time-growth curve. The cytotoxicity of SIM combined with polymyxin B sulfate [PB(S)] or polymyxin E (PE) in vitro was evaluated using CCK-8, human RBC hemolysis and scratch assays. In addition, we investigated the eradication of biofilm formation of S. aureus by biofilm inhibition assay and the killing of persister cells. Moreover, we evaluated the therapeutic effect and in vivo toxicity of the combination against MRSA in murine subcutaneous abscess model. Furthermore, it was preliminarily found that SIM significantly enhanced the destruction of MRSA membrane by SYTOX Green and DISC3(5) probes. In summary, these results reveal that the therapy of SIM combined with polymyxins (especially PE) is promising for the treatment of MRSA infection.

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Pixantrone Sensitizes Gram-Negative Pathogens to Rifampin

Abstract: Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health.

Cited by 6 publications

References 68 publications

Anti-staphylococcal activity of a polyphenol-rich citrus extract: synergy with β-lactams and low proficiency to induce resistance

Anti-staphylococcal activity of a polyphenol-rich citrus extract: synergy with β-lactams and low proficiency to induce resistance

Baicalein Resensitizes Multidrug-Resistant Gram-Negative Pathogens to Doxycycline

Simeprevir restores the anti-Staphylococcus activity of polymyxins

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