The use of 4-Hexylresorcinol as antibiotic adjuvant.

Adjuvants, Pharmaceutic / pharmacology Animals Anti-Bacterial Agents / pharmacology Disease Models, Animal Drug Resistance, Multiple, Bacterial Drug Synergism Drug Therapy, Combination / methods Escherichia coli / drug effects Female Hexylresorcinol / pharmacology Humans Klebsiella Infections / drug therapy Klebsiella pneumoniae / drug effects Mice Microbial Sensitivity Tests Polymyxins / pharmacology Sepsis / drug therapy Staphylococcus aureus / drug effects

Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 24 04 2020
accepted: 31 08 2020
entrez: 22 9 2020
pubmed: 23 9 2020
medline: 4 11 2020
Statut: epublish

Résumé

Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR.

Identifiants

DOI: 10.1371/journal.pone.0239147 PMID: 32960928 PMC: PMC7508414
pubmed: 32960928
doi: 10.1371/journal.pone.0239147
pii: PONE-D-20-09958
pmc: PMC7508414
doi:

Substances chimiques

Adjuvants, Pharmaceutic 0
Anti-Bacterial Agents 0
Polymyxins 0
Hexylresorcinol R9QTB5E82N

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0239147

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Y A Nikolaev (YA)

Federal Research Centre "Fundamentals of Biotechnology", Russian Academy of Sciences, Moscow, Russia.

A V Tutel'yan (AV)

Central Research Institute of Epidemiology of Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor) and I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.
ORCID: 0000-0002-2706-6689

N G Loiko (NG)

Federal Research Centre "Fundamentals of Biotechnology", Russian Academy of Sciences, Moscow, Russia.

J Buck (J)

Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
ORCID: 0000-0002-4676-3113

S V Sidorenko (SV)

Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russia.
I.I. Mechnikov North Western State Medical University, St Petersburg, Russia.

I Lazareva (I)

Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russia.
I.I. Mechnikov North Western State Medical University, St Petersburg, Russia.

V Gostev (V)

Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russia.
I.I. Mechnikov North Western State Medical University, St Petersburg, Russia.

O Y Manzen'yuk (OY)

State Research Center for Applied Microbiology and Biotechnology of Russian Federal Service for Surveillance on Consumer Rights Protection and Human Welfare (Rospotrebnadzor), Obolensk, Russia.

I G Shemyakin (IG)

State Research Center for Applied Microbiology and Biotechnology of Russian Federal Service for Surveillance on Consumer Rights Protection and Human Welfare (Rospotrebnadzor), Obolensk, Russia.

R A Abramovich (RA)

Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.

J Huwyler (J)

Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
ORCID: 0000-0003-1748-5676

G I El'-Registan (GI)

Federal Research Centre "Fundamentals of Biotechnology", Russian Academy of Sciences, Moscow, Russia.

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Classifications MeSH

Recherchemedicale.com › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Excipients pharmaceutiques › Adjuvants pharmaceutiques › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Eucaryotes › Animaux › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Multirésistance aux médicaments › Multirésistance bactérienne aux médicaments › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Interactions médicamenteuses › Synergie des médicaments › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Thérapeutique › Traitement médicamenteux › Association de médicaments › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Bactéries › Proteobacteria › Gammaproteobacteria › Enterobacteriaceae › Escherichia › Escherichia coli › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénols › Résorcinol › Hexylrésorcinol › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram négatif › Infections à Enterobacteriaceae › Infections à Klebsiella › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Bactéries › Proteobacteria › Gammaproteobacteria › Enterobacteriaceae › Klebsiella › Klebsiella pneumoniae › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité microbienne › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Perforines › Peptides antimicrobiens cationiques › Polymyxines › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Sepsie › The use of 4-Hexylresorcinol as antibiotic adjuvant.
Recherchemedicale.com › Bactéries › Bactéries à Gram positif › Cocci à Gram positif › Staphylococcaceae › Staphylococcus › Staphylococcus aureus › The use of 4-Hexylresorcinol as antibiotic adjuvant.