The combined antibacterial effects of sodium new houttuyfonate and berberine chloride against growing and persistent methicillin-resistant and vancomycin-intermediate Staphylococcus aureus

Abstract

Background Infections caused by drug-resistant Staphylococcus aureus, especially vancomycin-intermediate Staphylococcus aureus (VISA), leave clinicians with limited therapeutic options for treatment. Persister cells is a leading cause of recalcitrant infection and antibiotic treatment failure, and there is no drug in clinical use that specifically targets persister cells currently. Here, we report a promising combination therapy of sodium new houttuyfonate (SNH) and berberine chloride (BBR) which is able to eradicate both growing and persistent drug-resistant Staphylococcus aureus. Results The susceptibility test showed SNH exhibited anti-MRSA activity with MIC90 at 64 μg/mL, while BBR showed weak anti-MRSA activity with MIC90 at 512 μg/mL. MICs of BBR in combination with 1/2 MIC SNH decreased by 4 to 64 folds compared with MICs of BBR alone. The results of time-killing assays revealed that the combined use of sub-MIC SNH and BBR offered an in vitro synergistic action against growing MRSA (including pathogenic MRSA) and VISA strains. More importantly, the combination of SNH and BBR was able to eradicate VISA Mu50 and pathogenic MRSA persister cells. The synergistic effect is likely related to the interruption of the cell membrane caused by SNH, which is confirmed by scanning electron microscope and membrane potential and permeability analysis. Conclusions Our study provide a promising clinical curative strategy for combating drug-resistant S. aureus infections, especially for recalcitrant infections caused by persister cells.

Hemithioindigo‐Based Visible Light‐Activated Molecular Machines Kill Bacteria by Oxidative Damage

“…Cells were treated with 10× MIC linezolid for 24 h to eliminate active cells, after which persister cells were collected and washed to remove any trace of antibiotic. [ 27 ] Depending on the bacterial strain and HTI, persister cells could be eradicated in as little as 25 min with 1× MIC of HTI, outperforming conventional antibiotics at even 2× MIC (Figure 3C ). Treatment with 1× MIC of HTI also eradicated antibiotic‐tolerant persisters of MRSA in 35 min (HTI 5 , 6 , and 7 ) to 55 min (HTI 1 and 3 ) of light activation compared with an ≈1−log 10 reduction observed in DMSO‐treated samples even after 60 min of irradiation (Figure 3D ).…”

“…Antibiotic‐tolerant persisters were generated as previously described. [ 27 ] Briefly, bacterial cultures were grown with agitation (220 rpm) at the appropriate temperature (Table S1 , Supporting Information) in LB broth to an OD 600 ≈ 0.3. The cells were then diluted 1:1000 in fresh LB and grown for an additional 16 h at the appropriate temperature at 220 rpm.…”

Antifungal Activity of Sodium New Houttuyfonate Against Aspergillus fumigatus in vitro and in vivo

“…However, SNH has better clinical value and higher chemical stability than SH ( Zhao et al, 2020 ). Investigations have also confirmed that SNH exhibits antibacterial effects against Staphylococcus aureus and methicillin-resistant S. aureus ( Lu et al, 2013 ; Li et al, 2020 ), Streptococcus pneumoniae ( Yang et al, 2016 ), and C. albicans ( Wu et al, 2020 ). Although SNH acts as an anti-inflammatory medicine and has various anti-bacterial and anti- C. albicans activities, the anti-fungal effect against A. fumigatus , particularly various triazole-resistant strains, has not been reported.…”

Berberine in Sepsis: Effects, Mechanisms, and Therapeutic Strategies

“…For example, combinatorial liposomes of BBR and curcumin could inhibit biofilm formation and intracellular methicillin-resistant Staphylococcus aureus infections and associated inflammation, with five times more efficient than clindamycin [ 58 ]. The combined use of sodium new houttuyfonate and berberine chloride presented synergistic antibacterial effects against growing and persistent methicillin-resistant and vancomycin-intermediate Staphylococcus aureus , which is likely related to the interruption of the cell membrane [ 59 ]. These combined antibacterial effects of BBR with other agents predicted their potential application in sepsis.…”