Effect of High
            <i>N</i>
            -Acetylcysteine Concentrations on Antibiotic Activity against a Large Collection of Respiratory Pathogens

Landini, Giulia; Maggio, Tiziana Di; Sergio, Francesco; Docquier, Jean Denis; Rossolini, Gian María; Pallecchi, Lucia

doi:10.1128/aac.01334-16

Cited by 31 publications

(28 citation statements)

References 17 publications

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Section: Nac Reduces Cip-mediated Induction Of the Sos Responsesupporting

confidence: 93%

“…On the contrary, NAC alone inhibited bacterial growth without inducing the SOS response (Tukey multiple comparisons after significant ANOVA, P=0.0003). This result is in line with previous studies that reported NAC antibacterial properties against a range of bacterial pathogens (Jang, Bak, and Cha 2017;Landini et al 2016;Zhao and Liu 2010). Additionally, we verified that the differences in the final optical density observed upon different treatments do not directly bias SOS induction measured as GFP fluorescence (Supplementary figure S3).…”

Section: Nac Reduces Cip-mediated Induction Of the Sos Responsesupporting

confidence: 92%

“…We have shown that physiologically attainable concentrations of NAC inhibited SOS induction without compromising CIP bactericidal activity. On the contrary, NAC itself has been shown to present antibacterial properties against Helicobacter pylori (Jang, Bak, and Cha 2017), Haemophilus influenzae (Landini et al 2016) and Pseudomonas aeruginosa biofilms (Zhao and Liu 2010). From the clinical point of view, inhibition of SOS induction could provide several important benefits besides reducing mutagenesis.…”

Section: Discussionmentioning

confidence: 99%

“…NAC is clinically safe and is currently used in humans therapy to treat numerous disorders (34). Additionally, NAC does not negatively affect the activity of major antibiotic classes, with the exception of carbapenems (36,37). On the contrary, NAC has shown antimicrobial properties against a range of clinicallyrelevant pathogens (38)(39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

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The antioxidant drug N-acetylcysteine abolishes SOS-mediated mutagenesis produced by fluoroquinolones in bacteria

Rodríguez‐Rojas

et al. 2018

Preprint

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Certain antibiotics, particularly fluoroquinolones, induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS), which have been correlated with antibiotic lethality. Both SOS and ROS increase mutagenesis in treated bacteria, likely resulting in the appearance of resistant mutants during antibiotic treatments. However, the relative contribution of ROS and SOS on this antibiotic-mediated mutagenesis is currently unknown. We used the antioxidant molecule N-acetylcysteine (NAC) to study the contribution of ROS on the SOS response and mutagenesis mediated by the fluoroquinolone antibiotic ciprofloxacin (CIP). We show that NAC is able to reduce intracellular ROS levels, mitigating as well the SOS response caused by treatment with subinhibitory concentrations of CIP. This effect leads to the reduction of antibiotic-induced mutagenesis to levels comparable to a translesion DNA-polymerases (TLS) deficient strain, suggesting that ROS play a major role in SOS-induced mutagenesis. Collectively, our results shed light on the mechanisms underlying antibiotic-induced mutagenesis and pave the way for the use of NAC as a safe adjuvant in antibiotic therapy to inhibit antibiotic-induced mutagenesis, hence augmenting our capacity to fight against threatening bacterial infections.

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Section: Nac Reduces Cip-mediated Induction Of the Sos Responsesupporting

confidence: 93%

Section: Nac Reduces Cip-mediated Induction Of the Sos Responsesupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The antioxidant drug N-acetylcysteine abolishes SOS-mediated mutagenesis produced by fluoroquinolones in bacteria

Rodríguez‐Rojas

et al. 2018

Preprint

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“…It is usually used as a mucolytic agent and an antioxidant to react with mucous bronchial secretions and free radicals. NAC can affect the stability and compromise the activity of carbapenems [32]. It also decreases the activity of coagulation factors in plasma, and intravenous NAC may interfere with the sulfhydryl groups on these factors [25, 33].…”

Section: Discussionmentioning

confidence: 99%

The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial Biofilm Formation

Yin

Jiang

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: N-acetylcysteine (NAC) is a novel and promising agent with activity against bacterial biofilms. Human serum also inhibits biofilm formation by some bacteria. We tested whether the combination of NAC and human serum offers greater anti-biofilm activity than either agent alone. Methods: Microtiter plate assays and confocal laser scanning microscopy were used to evaluate bacterial biofilm formation in the presence of NAC and human serum. qPCR was used to examine expression of selected biofilm-associated genes. Extracellular matrix (ECM) was observed by transmission electron microscopy. The antioxidants GSH or ascorbic acid were used to replace NAC, and human transferrin, lactoferrin, or bovine serum albumin were used to replace serum proteins in biofilm formation assays. A rat central venous catheter model was developed to evaluate the effect of NAC on biofilm formation in vivo. Results: NAC and serum together increased biofilm formation by seven different bacterial strains. In Staphylococcus aureus, expression of genes for some global regulators and for genes in the ica-dependent pathway increased markedly. In Pseudomonas aeruginosa, transcription of las, the PQS quorum sensing (QS) systems, and the two-component system GacS/GacA increased significantly. ECM production by S. aureus and P. aeruginosa was also enhanced. The potentiation of biofilm formation is due mainly to interaction between NAC and transferrin. Intravenous administration of NAC increased colonization by S. aureus and P. aeruginosa on implanted catheters. Conclusions: NAC used intravenously or in the presence of blood increases bacterial biofilm formation rather than inhibits it.

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Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial

Panahi

Ghanei

Rahimi

et al. 2022

Journal of Medical Virology

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The aim of this study was to evaluate the effect and safety of N‐acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID‐19). This randomized controlled clinical trial study was conducted on patients with COVID‐19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C‐reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID‐19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus‐2 is limited and further research is required.

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Effect of High N -Acetylcysteine Concentrations on Antibiotic Activity against a Large Collection of Respiratory Pathogens

Cited by 31 publications

References 17 publications

The antioxidant drug N-acetylcysteine abolishes SOS-mediated mutagenesis produced by fluoroquinolones in bacteria

The antioxidant drug N-acetylcysteine abolishes SOS-mediated mutagenesis produced by fluoroquinolones in bacteria

The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial Biofilm Formation

Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial

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