Ursolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae

Sundaramoorthy, Niranjana Sri; Mohan, Harihar Milaganur; Subramaniam, Shankar; Raman, Thiagarajan; Ganesan, Subramaniapillai Selva; Sivasubamanian, Aravind; Nagarajan, Saisubramanian

doi:10.1186/s13568-019-0750-4

Cited by 26 publications

(16 citation statements)

References 43 publications

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“…On MRSA, synergy has been described with ampicillin and oxacillin [ 7 ]. Similar observations were also reported for B. cereus (synergy with ampicillin and tetracycline [ 12 ]), Staphylococcus epidermidis (synergy with β-lactams [ 2 ]), Listeria monocytogenes (synergy with β-lactams [ 2 ]), Escherichia coli (synergy with kanamycin [ 14 ]), and colistin-resistant Enterobacteriacae (synergy with colistin [ 4 ]).…”

Section: Introductionsupporting

confidence: 72%

“…Two main representative compounds are ursolic acid (UA) (3β-hydroxy-urs-12-en-28-oic acid) and oleanolic acid (OA) (3β-hydroxy-olean-12-en-28-oic acid). Both show an antimicrobial activity against a large number of pathogens including carbapenem-resistant Klebsiella pneumoniae [ 3 ], colistin-resistant Enterobacteriaceae [ 4 ], vancomycin-resistant enterococci [ 5 ], Porphyromonas gingivalis [ 6 ], MRSA [ 7 ], or Streptococcus mutans biofilm [ 8 ]. In addition, stimulation of immunomodulatory properties [ 9 ], inhibition of peptidoglycan metabolism [ 10 ], prevention of cell division [ 10 ], and inhibition of efflux pumps [ 11 ] were reported.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

et al. 2021

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Staphylococcus aureus is an opportunistic pathogen and the major causative agent of life-threatening hospital- and community-acquired infections. A combination of antibiotics could be an opportunity to address the widespread emergence of antibiotic-resistant strains, including Methicillin-Resistant S. aureus (MRSA). We here investigated the potential synergy between ampicillin and plant-derived antibiotics (pentacyclic triterpenes, ursolic acid (UA) and oleanolic acid (OA)) towards MRSA (ATCC33591 and COL) and the mechanisms involved. We calculated the Fractional Inhibitory Concentration Index (FICI) and demonstrated synergy. We monitored fluorescence of Bodipy-TR-Cadaverin, propidium iodide and membrane potential-sensitive probe for determining the ability of UA and OA to bind to lipoteichoic acids (LTA), and to induce membrane permeabilization and depolarization, respectively. Both pentacyclic triterpenes were able to bind to LTA and to induce membrane permeabilization and depolarization in a dose-dependent fashion. These effects were not accompanied by significant changes in cellular concentration of pentacyclic triterpenes and/or ampicillin, suggesting an effect mediated through lipid membranes. We therefore focused on membranous effects induced by UA and OA, and we investigated on models of membranes, the role of specific lipids including phosphatidylglycerol and cardiolipin. The effect induced on membrane fluidity, permeability and ability to fuse were studied by determining changes in fluorescence anisotropy of DPH/generalized polarization of Laurdan, calcein release from liposomes, fluorescence dequenching of octadecyl-rhodamine B and liposome-size, respectively. Both UA and OA showed a dose-dependent effect with membrane rigidification, increase of membrane permeabilization and fusion. Except for the effect on membrane fluidity, the effect of UA was consistently higher compared with that obtained with OA, suggesting the role of methyl group position. All together the data demonstrated the potential role of compounds acting on lipid membranes for enhancing the activity of other antibiotics, like ampicillin and inducing synergy. Such combinations offer an opportunity to explore a larger antibiotic chemical space.

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Section: Introductionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

et al. 2021

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“…As the fight against multidrug resistance continues, concerted efforts by agencies, health care systems and biomedical scientist are restlessly exploring possible alternatives that might suffice pending the discovery and development of novel antibacterial agents that could effectively curb the spread of antibiotics resistance. The use of antibiotics combinations [13][14][15], efflux pump inhibitors [16][17][18], and resistance modifying agents [19,20] are suggested as temporary control measures to reverse microbial resistance or enhance the inactivation of resistant bacterial isolates. Antibiotics combination therapy is proposed as a reliable option with demonstrated results against multidrug resistant bacterial isolates.…”

Section: Introductionmentioning

confidence: 99%

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

et al. 2021

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Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

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“…The zebrafish infection model proved to be beneficial for human bacterial infections. Studies were performed earlier to evaluate the antimicrobial potential of natural compounds in vivo in zebrafish 38 . In this assay, the combination of BCl, RUT, and streptomycin showed promising results against B. subtilis induced infection in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial potential of selected phytomolecules: An experimental study

Jhanji

Singh

Kumar

2021

Microbiology and Immunology

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Antibiotic resistance is a snowballing international threat. Some of the antibiotics have lost their effectiveness due to overuse and underuse. Thus, there is an urgent need to tackle this global challenge, either by inhibiting the resistance mechanisms or by the development of new chemical entities. Thus, in the current study, the antibacterial activity of selected phytomolecules was investigated against bacterial strains, alone and in combination, with standard drugs. The antibacterial potential of these phytomolecules was explored using in vitro assays (microtiter assay, bacterial growth kinetics, percentage retardation of growth, and antimicrobial synergy study) and in vivo studies (zebrafish infection model). In vitro and in vivo studies have shown promising antibacterial effects against, both, Gram‐positive and Gram‐negative bacteria. Moreover, a cell viability assay also indicated the cytoprotective effect of these phytomolecules in combination with standard antibiotics (SABX). Thus, these phytomolecules could be a promising broad‐spectrum antibacterial agent in combination with standard antibiotics.

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Ursolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae

Cited by 26 publications

References 43 publications

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

Antibacterial potential of selected phytomolecules: An experimental study

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