Disruption of biofilms and killing of Burkholderia cenocepacia from cystic fibrosis lung using an antioxidant-antibiotic combination therapy

Aiyer, Aditi; Manoharan, Arthika; Paino, Denis; Farrell, Jessica; Whiteley, Greg S.; Kriel, Frederik H.; Glasbey, Trevor; Manos, Jim; Das, Theerthankar

doi:10.1016/j.ijantimicag.2021.106372

Cited by 17 publications

(11 citation statements)

References 34 publications

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“…It has been studied in combination with NAC in its intrinsic acidic pH form and has shown some reductions in CFU/mL. In a previous study by our group, we showed that acidic NAC in combination with the MIC of ciprofloxacin was able to reduce the bacterial loads more than the antibiotic alone in B. cenocepacia isolates [36]. In this former study we concentrated on combinations with acidic NAC and their synergism was not fully investigated.…”

Section: Discussionmentioning

confidence: 99%

“…MIC was defined as the lowest concentration of antimicrobial to inhibit planktonic growth, as determined by the broth microdilution method [36,49]. The effects of the antioxidant and antibiotics on isolates were determined by inoculating diluted bacterial cultures in TSB into 96-well plates (Corning Corp., New York, NY, USA).…”

Section: Effect Of Antioxidant and Antibiotics Against Planktonic Bacteriamentioning

confidence: 99%

“…The MBIC of individual antibiotics and antioxidants on irreversibly attached bacteria were determined using previously detailed methods with modifications [36,52]. Briefly, the MBIC values for bacteria were determined using 200 µL of diluted bacterial culture added to 96-well plates (Corning Corp., New York, NY, USA) and incubated for 2 h at 37 • C (100 rpm), for irreversible bacterial attachment.…”

Section: Effect Of Antioxidant and Antibiotics On Prevention Of Biofilm Maturation Following Irreversible Bacterial Attachmentmentioning

confidence: 99%

“…Time-kill bactericidal activity assays were performed on all tested strains, as described previously [36]. The bacteriostatic or bactericidal effect of NAC, defined as termination or killing of bacteria, respectively, was determined by inoculating TSB-diluted cultures in 96-well flat-bottomed plates in the presence of final concentrations in Table 3.…”

Section: Time-kill Assay Of Single Versus Combination Treatments Against Planktonic Culturesmentioning

confidence: 99%

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Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance

et al. 2021

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Cystic fibrosis (CF) is a genetic disorder causing dysfunctional ion transport resulting in accumulation of viscous mucus that fosters chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans and Stenotrophomonas maltophilia are increasingly prevalent CF pathogens and while Burkholderia cencocepacia is slowly decreasing; all are complicated by multidrug resistance that is enhanced by biofilm formation. This study investigates potential synergy between the antibiotics ciprofloxacin (0.5–128 µg/mL), colistin (0.5–128 µg/mL) and tobramycin (0.5–128 µg/mL) when combined with the neutral pH form of N-Acetylcysteine (NACneutral) (0.5–16.3 mg/mL) against 11 cystic fibrosis strains of Burkholderia, Stenotrophomonas and Achromobacter sp. in planktonic and biofilm cultures. We screened for potential synergism using checkerboard assays from which fraction inhibitory concentration indices (FICI) were calculated. Synergistic (FICI ≤ 0.5) and additive (0.5 > FICI ≥ 1) combinations were tested on irreversibly attached bacteria and 48 h mature biofilms via time-course and colony forming units (CFU/mL) assays. This study suggests that planktonic FICI analysis does not necessarily translate to reduction in bacterial loads in a biofilm model. Future directions include refining synergy testing and determining further mechanisms of action of NAC to understand how it may interact with antibiotics to better predict synergy.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Antioxidant and Antibiotics Against Planktonic Bacteriamentioning

confidence: 99%

Section: Effect Of Antioxidant and Antibiotics On Prevention Of Biofilm Maturation Following Irreversible Bacterial Attachmentmentioning

confidence: 99%

Section: Time-kill Assay Of Single Versus Combination Treatments Against Planktonic Culturesmentioning

confidence: 99%

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Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance

et al. 2021

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“…So far, several studies have shown in vitro antibacterial and antibiofilm activity of NAC against both Gram-positive and Gram-negative microorganisms, including, amongst others, relevant difficult-to-treat pathogens such as P. aeruginosa , S. maltophilia and the Burkholderia cepacia complex [ 12 , 14 , 15 , 16 , 17 , 18 , 19 ]. More recently, Pollini et al showed a potent synergism between NAC and colistin against colistin-resistant CR-Ab, whereas no activity was observed when the strains were susceptible to colistin.…”

Section: Discussionmentioning

confidence: 99%

High Activity of N-Acetylcysteine in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii

et al. 2022

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Aim: The aim of the study was to evaluate the in vitro activity of N-acetylcysteine (NAC), alone or in combination with beta-lactams, against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab). Methods: The antibacterial activity of each compound was tested by broth microdilution and the synergism was evaluated by the checkerboard method. Killing studies of NAC alone and in combination with beta-lactams were performed. Bacterial morphological changes were investigated with scanning electron microscopy (SEM). Results: Overall, 30 strains were included (15 CR-Kp and 15 CR-Ab). The NAC Minimal Inhibitory Concentrations (MIC)50/90 were 5/5 and 2.5/5 mg/mL for CR-Kp and CR-Ab, respectively. For both microorganisms, NAC, in addition to beta-lactams (meropenem for CR-Kp, meropenem and ampicillin/sulbactam for CR-Ab, respectively), was able to enhance their activity. The killing studies showed a rapid and concentration-dependent activity of NAC alone; the addition of NAC to meropenem or ampicillin/sulbactam at subinhibitory concentrations induced a fast and lasting bactericidal activity that persisted over time. The SEM analyses showed evident morphological alterations of the bacterial cells following incubation with NAC, alone and in combination with meropenem. Conclusions: NAC demonstrated a high in vitro activity against CR-Kp and CR-Ab and was able to enhance beta-lactams’ susceptibility in the tested strains. The preliminary data on the SEM analyses confirmed the in vitro results.

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Impact of N-Acetylcysteine and Antibiotics Against Single and Dual Species Biofilms of Pseudomonas aeruginosa and Achromobacter xylosoxidans

2022

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Disruption of biofilms and killing of Burkholderia cenocepacia from cystic fibrosis lung using an antioxidant-antibiotic combination therapy

Cited by 17 publications

References 34 publications

Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance

Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance

High Activity of N-Acetylcysteine in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii

Impact of N-Acetylcysteine and Antibiotics Against Single and Dual Species Biofilms of Pseudomonas aeruginosa and Achromobacter xylosoxidans

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