Synthesis of the cyanobacterial halometabolite Chlorosphaerolactylate B and demonstration of its antimicrobial effect in vitro and in vivo .

Autor:	Jensen N; Section for Pathobiological Sciences, Department of Veterinary and Animal Science, University of Copenhagen, Copenhagen, Denmark., Jensen HE; Section for Pathobiological Sciences, Department of Veterinary and Animal Science, University of Copenhagen, Copenhagen, Denmark., Aalbaek B; Section for Pathobiological Sciences, Department of Veterinary and Animal Science, University of Copenhagen, Copenhagen, Denmark., Blirup-Plum SA; Section for Pathobiological Sciences, Department of Veterinary and Animal Science, University of Copenhagen, Copenhagen, Denmark., Soto SM; ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.; CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Cepas V; ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain., López Y; ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain., Gabasa Y; ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain., Gutiérrez-Del-Río I; Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC, Department of Functional Biology, University of Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Villar CJ; Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC, Department of Functional Biology, University of Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Lombó F; Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC, Department of Functional Biology, University of Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Iglesias MJ; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Soengas R; Área de Química Orgánica, Centro de Investigación CIAIMBITAL, Universidad de Almería, Almería, Spain., López Ortiz F; Área de Química Orgánica, Centro de Investigación CIAIMBITAL, Universidad de Almería, Almería, Spain., Jensen LK; Section for Pathobiological Sciences, Department of Veterinary and Animal Science, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2022 Sep 29; Vol. 13, pp. 950855. Date of Electronic Publication: 2022 Sep 29 (Print Publication: 2022).
DOI:	10.3389/fmicb.2022.950855
Abstrakt:	Chlorosphaerolactylate B, a newly discovered antimicrobial halometabolite from the cyanobacterium Sphaerospermopsis sp. LEGE 00249 has been synthesized in three steps by using 12-bromododecanoic acid as starting material. A total of 0.5 g was produced for in vitro and in vivo antimicrobial efficacy testing. In vitro , the minimal inhibitory concentration (MIC) was estimated to be 256 mg/L for Staphylococcus aureus , while the minimal biofilm inhibitory concentration (MBIC) was estimated to be 74 mg/L. The in vivo study utilized a porcine model of implant-associated osteomyelitis. In total, 12 female pigs were allocated into 3 groups based on inoculum ( n = 4 in each group). An implant cavity (IC) was drilled in the right tibia and followed by inoculation and insertion of a steel implant. All pigs were inoculated with 10 μL containing either: 11.79 mg synthetic Chlorosphaerolactylate B + 10 4 CFU of S. aureus (Group A), 10 4 CFU of S. aureus (Group B), or pure saline (Group C), respectively. Pigs were euthanized five days after inoculation. All Group B animals showed macroscopic and microscopic signs of bone infection and both tissue and implant harbored S. aureus bacteria (mean CFU on implants = 1.9 × 10 5 ). In contrast, S. aureus could not be isolated from animals inoculated with saline. In Group A, two animals had a low number of S. aureus (CFU = 6.7 × 10 1 and 3.8 × 10 1 , respectively) on the implants, otherwise all Group A animals were similar to Group C animals. In conclusion, synthetic Chlorosphaerolactylate B holds potential to be a novel antimicrobial and antibiofilm compound. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Jensen, Jensen, Aalbaek, Blirup-Plum, Soto, Cepas, López, Gabasa, Gutiérrez-del-Río, Villar, Lombó, Iglesias, Soengas, López Ortiz and Jensen.)
Databáze:	MEDLINE
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