Synthesis of the cyanobacterial halometabolite chlorosphaerolactylate B and demonstration of its antimicrobial effect in vitro and in vivo
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Synthesis of the cyanobacterial halometabolite chlorosphaerolactylate B and demonstration of its antimicrobial effect in vitro and in vivo. / Jensen, Nikoline; Jensen, Henrik Elvang; Aalbaek, Bent; Blirup-Plum, Sophie Amalie; Soto, Sara M; Cepas, Virginio; López, Yuly; Gabasa, Yaiza; Gutiérrez-Del-Río, Ignacio; Villar, Claudio J; Lombó, Felipe; Iglesias, María José; Soengas, Raquel; López Ortiz, Fernando; Jensen, Louise Kruse.
In: Frontiers in Microbiology, Vol. 13, 950855, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synthesis of the cyanobacterial halometabolite chlorosphaerolactylate B and demonstration of its antimicrobial effect in vitro and in vivo
AU - Jensen, Nikoline
AU - Jensen, Henrik Elvang
AU - Aalbaek, Bent
AU - Blirup-Plum, Sophie Amalie
AU - Soto, Sara M
AU - Cepas, Virginio
AU - López, Yuly
AU - Gabasa, Yaiza
AU - Gutiérrez-Del-Río, Ignacio
AU - Villar, Claudio J
AU - Lombó, Felipe
AU - Iglesias, María José
AU - Soengas, Raquel
AU - López Ortiz, Fernando
AU - Jensen, Louise Kruse
N1 - Copyright © 2022 Jensen, Jensen, Aalbaek, Blirup-Plum, Soto, Cepas, López, Gabasa, Gutiérrez-del-Río, Villar, Lombó, Iglesias, Soengas, López Ortiz and Jensen.
PY - 2022
Y1 - 2022
N2 - 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 + 104 CFU of S. aureus (Group A), 104 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 × 105). 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 × 101 and 3.8 × 101, 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.
AB - 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 + 104 CFU of S. aureus (Group A), 104 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 × 105). 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 × 101 and 3.8 × 101, 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.
U2 - 10.3389/fmicb.2022.950855
DO - 10.3389/fmicb.2022.950855
M3 - Journal article
C2 - 36246241
VL - 13
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
M1 - 950855
ER -
ID: 323571147