Exploration of the antibiotic potentiating activity of indolglyoxylpolyamines

Cadelis, Melissa M.; Pike, Elliot I.W.; Kang, Weirong; Wu, Zimei; Bourguet‐Kondracki, Marie‐Lise; Blanchet, Marine; Vidal, Nicolás; Brunel, Jean Michel; Copp, Brent R.

doi:10.1016/j.ejmech.2019.111708

Cited by 15 publications

(25 citation statements)

References 21 publications

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“…This principle is applied in ameliorating the current antibiotherapy system. When potential bio-compounds are co-dosed with antibiotics, the activity of the antibiotics is enhanced towards the bacteria that were initially developing resistance [ 23 ]. We aimed to further investigate the most active microbial inhibitor (BTE) defined by antimicrobial assay for its potentiating activity with three commercial antibiotics: chloramphenicol, ciprofloxacin and streptomycin.…”

Section: Resultsmentioning

confidence: 99%

Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

et al. 2021

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The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19–0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.

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Section: Resultsmentioning

confidence: 99%

Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

et al. 2021

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“…Despite the promising start, research on polyamines in host-microbe interactions fell into a long lull from the 1980s to the 2000s. Recently, a mini-renaissance of interest in polyamines and microbial pathogenesis may have begun [59][60][61]. ApCM is a mixture of colonoid-secreted molecules and mucus.…”

Section: Discussionmentioning

confidence: 99%

Cross-Talk between Probiotic Nissle 1917 and Human Colonic Epithelium Affects the Metabolite Composition and Demonstrates Host Antibacterial Effect

et al. 2021

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Colonic epithelium–commensal interactions play a very important role in human health and disease development. Colonic mucus serves as an ecologic niche for a myriad of commensals and provides a physical barrier between the epithelium and luminal content, suggesting that communication between the host and microbes occurs mainly by soluble factors. However, the composition of epithelia-derived metabolites and how the commensal flora influences them is less characterized. Here, we used mucus-producing human adult stem cell-derived colonoid monolayers exposed apically to probiotic E. coli strain Nissle 1917 to characterize the host–microbial communication via small molecules. We measured the metabolites in the media from host and bacterial monocultures and from bacteria-colonoid co-cultures. We found that colonoids secrete amino acids, organic acids, nucleosides, and polyamines, apically and basolaterally. The metabolites from host-bacteria co-cultures markedly differ from those of host cells grown alone or bacteria grown alone. Nissle 1917 affects the composition of apical and basolateral metabolites. Importantly, spermine, secreted apically by colonoids, shows antibacterial properties, and inhibits the growth of several bacterial strains. Our data demonstrate the existence of a cross-talk between luminal bacteria and human intestinal epithelium via metabolites, which might affect the numbers of physiologic processes including the composition of commensal flora via bactericidal effects.

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“…Different authors have reported the use of adjuvants to decrease the MIC of resistant bacteria using antibiotics against different Gram-positive and Gram-negative bacteria (Kim et al, 2018;Baker et al, 2019). These authors determined that the sensitizer effect observed for these compounds can be explained with their capacity to alter the stability/function of the outer or cytoplasmic membrane (Cadelis et al, 2019;French et al, 2019). Such is the case for transition metal ions, included the ones used in this work, which have been reported to disrupt these cellular structures including the outer and the cytoplasmic membrane (Lemire et al, 2013).…”

Section: Antimicrobial Effect Of the Atmcs In Resistant Bacteriamentioning

confidence: 99%

Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations

Garza-Cervantes

Meza-Bustillos

Resendiz-Hernández

et al. 2020

Front. Bioeng. Biotechnol.

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Due to the recent emergence of multi-drug resistant strains, the development of novel antimicrobial agents has become a critical issue. The use of micronutrient transition metals is a promising approach to overcome this problem since these compounds exhibit significant toxicity at low concentrations in prokaryotic cells. In this work, we demonstrate that at concentrations lower than their minimal inhibitory concentrations and in combination with different antibiotics, it is possible to mitigate the barriers to employ metallic micronutrients as therapeutic agents. Here, we show that when administered as a combinatorial treatment, Cu 2+ , Zn 2+ , Co 2+ , Cd 2+ , and Ni 2+ increase susceptibility of Escherichia coli and Staphylococcus aureus to ampicillin and kanamycin. Furthermore, ampicillin-resistant E. coli is re-sensitized to ampicillin when the ampicillin is administered in combination with Cu 2+ , Cd 2+ , or Ni 2 . Similarly, Cu 2+ , Zn 2+ , or Cd 2+ re-sensitize kanamycin-resistant E. coli and S. aureus to kanamycin when administered in a combinatorial treatment with those transition metals. Here, we demonstrate that for both susceptible and resistant bacteria, transition-metal micronutrients, and antibiotics interact synergistically in combinatorial treatments and exhibit increased effects when compared to the treatment with the antibiotic alone. Moreover, in vitro and in vivo assays, using a murine topical infection model, showed no toxicological effects of either treatment at the administered concentrations. Lastly, we show that combinatorial treatments can clear a murine topical infection caused by an antibiotic-resistant strain. Altogether, these results suggest that antibiotic-metallic micronutrient combinatorial treatments will play an important role in future developments of antimicrobial agents and treatments against infections caused by both susceptible and resistant strains.

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Exploration of the antibiotic potentiating activity of indolglyoxylpolyamines

Cited by 15 publications

References 21 publications

Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

Cross-Talk between Probiotic Nissle 1917 and Human Colonic Epithelium Affects the Metabolite Composition and Demonstrates Host Antibacterial Effect

Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations

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