A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii

Abstract

Multidrug-resistant (MDR) Acinetobacter baumannii strains can cause severe infections in intensive care units, and are rapidly developing resistance to the last-resort of existing antibiotics, posing a major global threat to health care system. Berberine hydrochloride (BBH), a kind of isoquinoline alkaloids extracted from Berberis and other plants, has been widely used as an antibacterial medicine for its reliable therapeutic efficiency. The in vitro synergistic effects of BBH with antibiotics against MDR A. baumannii were determined. BBH alone had weak antimicrobial activity (e.g., MIC≥256 mg/L) against MDR A. baumannii. However, it dramatically increased the susceptibility of MDR strains against antibiotics with FICI values <0.5, even reversed their resistance to antibiotics (e.g., tigecycline, sulbactam, meropenem and ciprofloxacin). In vivo study has suggested BBH with sulbactam had stronger antimicrobial efficiency than monotherapy in a neutropenic murine thigh infection model. The antibiotic-sensitizing mechanism of action of BBH was evaluated as well. BBH boosted adeB gene expression and bound to the AdeB transporter protein, resulting in low uptake of BBH, which may contribute to less extrusion of antibiotics by the AdeABC pump. Knockout of the adeB gene increased uptake of BBH and diminished the antibiotic sensitization and synergistic effects between antibiotics and BBH in MDR strains. Together, BBH effectively re-sensitizes this MDR pathogen to a range of antibiotics that have become barely effective due to antibiotic resistance, which indicates BBH may be a promising therapeutic adjuvant candidate to combat MDR A. baumannii.

Gut Microbiota: The Potential Key Target of TCM’s Therapeutic Effect of Treating Different Diseases Using the Same Method—UC and T2DM as Examples

“…As described in Tables 1 , 2 , most TCMs, such as curcumin and Rhizoma atractylodis macrocephalae , restore the diversity of flora, which may be one of the factors for treating different diseases using the same method. However, berberine (the main component of Rhizoma Coptidis) was confirmed to reduce bacterial diversity in both UC and T2DM models, possibly be due to its strong antibacterial efficacy ( Li et al., 2021b ), and its therapeutic effect on UC and T2DM may be similar to that of antibiotics. In addition, Huanglian Jiedu decoction, which uses Huanglian as the main drug, also reduced the bacterial diversity in UC mice.…”

NMPA-approved traditional Chinese medicine-Pingwei Pill: new indication for colistin recovery against MCR-positive bacteria infection

“…As expected, Pingwei Pill in combination with colistin increased body weights, alleviated pathological injury and the inflammatory response in the ceca and reduced the bacterial burden in the ceca of infected animals. Superior to most other combined therapies [19,29,[36][37][38], the suspension of Pingwei Pill and colistin in 0.5% CMC-Na was used for intragastric administration to fight the intestinal infection, which avoided the consideration of the C max and T max coincidence of these two drugs. Although 30% survival was observed for chick infection with combination therapy, the median survival prolonged from 72 h in model group to120h in combination group calculated by the GraphPad prism software 8.0.2, which further verified the efficacy of synergistic effect of Pingwei Pill with colistin.…”

Effects of berberine on the pharmacokinetics of florfenicol and levels of cytochrome P450 3A37, multidrug resistance 1, and chicken xenobiotic‐sensing orphan nuclear receptor mRNA expression in broilers

“…X. Li et al (2021) reported that BBR hydrochloride could reverse the resistance of multidrug-resistant Acinetobacter baumannii to tigecycline, sulbactam, meropenem, and ciprofloxacin. Shi et al (2018) indicated that the combination of BBR and ciprofloxacin has a synergistic antibiofilm effect on multi-resistant Salmonella via inhibiting the mRNA expressions of luxS, rpoE, and ompR.…”

“…X. Li et al. ( 2021 ) reported that BBR hydrochloride could reverse the resistance of multidrug‐resistant Acinetobacter baumannii to tigecycline, sulbactam, meropenem, and ciprofloxacin. Shi et al.…”