Antibacterial Compounds Against Non-Growing and Intracellular Bacteria DOI Creative Commons
Niilo Kaldalu,

Normunds Bērziņš,

Stina Berglund Fick

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Abstract Slow- and non-growing bacterial populations, along with intracellular pathogens, often evade standard antibacterial treatments are linked to persistent recurrent infections. This necessitates the development of therapies specifically targeting nonproliferating bacteria. To identify compounds active against uropathogenic Escherichia coli (UPEC) we performed a drug-repurposing screen 6,454 approved drugs drug candidates. Using dilution-regrowth assays, identified 39 that either kill UPEC or delay its regrowth post-treatment. The hits include fluoroquinolones, macrolides, rifamycins, biguanide disinfectants, pleuromutilin, anti-cancer agents. 29 have not previously been recognized as were further tested Pseudomonas aeruginosa Staphylococcus aureus. Ten – solithromycin, rifabutin, mitomycin C, seven fluoroquinolones strong bactericidal activity P. aeruginosa, killing > 4 log10 bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, satraplatin unique in their ability selectively target bacteria, exhibiting poor efficacy growing Finally, 31 hit inhibit growth Shigella flexneri human enterocyte infection model, indicating permeate cytoplasm host cells. hold potential for treating infections, warranting comparative studies current standard-of-care antibiotics.

Language: Английский

Microbes Saving Lives and Reducing Suffering DOI Creative Commons
Kenneth N. Timmis, Zeynep Ceren Karahan, Juan L. Ramos

et al.

Microbial Biotechnology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 1, 2025

Language: Английский

Citations

4
Efficacy of rifampicin combination therapy against MRSA prosthetic vascular graft infections in a rat model DOI Creative Commons
Mikkel Illemann Johansen,

Maiken Engelbrecht Petersen,

Emma Faddy

et al.

Biofilm, Journal Year: 2024, Volume and Issue: 7, P. 100189 - 100189

Published: Feb. 29, 2024

Staphylococcus aureus is a major cause of prosthetic vascular graft infections (VGEIs) and the optimal choice antibiotics unclear. We investigated various antibiotic choices as either monotherapy or combination therapy with rifampicin against MRSA in vitro vivo. Fosfomycin, daptomycin vancomycin alone was used USA300 FPR3757. Each tested for synergism antagonism vitro, all regimens were actively growing bacteria media non-growing buffer, both planktonic cells biofilms. A rat model VGEI to quantify therapeutic efficacy vivo by measuring bacterial load on grafts spleen, liver kidneys. In combinations did not reveal any relation growth inhibition. However, quantification bactericidal activity revealed strong antagonistic effect, biofilms cells. This effect only observed when treating active bacteria, had little no inactive Only showed some biocidal evaluation contrasted results. Rifampicin significantly increased vancomycin. The far most effective, curing 8 13 infected animals. Our study demonstrates that shows promising potential caused MRSA. Furthermore, we show how laboratory does predict their vivo, presumable due difference metabolic state bacteria.

Language: Английский

Citations

3
Antibacterial compounds against non-growing and intracellular bacteria DOI Creative Commons
Niilo Kaldalu,

Normunds Bērziņš,

Stina Berglund Fick

et al.

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: April 11, 2025

Language: Английский

Citations

0
Antibacterial Compounds Against Non-Growing and Intracellular Bacteria DOI Creative Commons
Niilo Kaldalu,

Normunds Bērziņš,

Stina Berglund Fick

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

ABSTRACT Slow- and non-growing bacterial populations, along with intracellular pathogens, often evade standard antibacterial treatments are linked to persistent recurrent infections. This necessitates the development of therapies specifically targeting nonproliferating bacteria. To identify compounds active against uropathogenic Escherichia coli (UPEC) we performed a drug-repurposing screen 6,454 approved drugs drug candidates. Using dilution-regrowth assays, identified 39 that either kill UPEC or delay its regrowth post-treatment. The hits include fluoroquinolones, macrolides, rifamycins, biguanide disinfectants, pleuromutilin, anti-cancer agents. 29 have not previously been recognized as were further tested Pseudomonas aeruginosa Staphylococcus aureus . Ten – solithromycin, rifabutin, mitomycin C, seven fluoroquinolones strong bactericidal activity P. , killing >4 log 10 bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, satraplatin unique in their ability selectively target bacteria, exhibiting poor efficacy growing Finally, 31 hit inhibit growth Shigella flexneri human enterocyte infection model, indicating permeate cytoplasm host cells. hold potential for treating infections, warranting comparative studies current standard-of-care antibiotics.

Language: Английский

Citations

0
Antibacterial Compounds Against Non-Growing and Intracellular Bacteria DOI Creative Commons
Niilo Kaldalu,

Normunds Bērziņš,

Stina Berglund Fick

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Abstract Slow- and non-growing bacterial populations, along with intracellular pathogens, often evade standard antibacterial treatments are linked to persistent recurrent infections. This necessitates the development of therapies specifically targeting nonproliferating bacteria. To identify compounds active against uropathogenic Escherichia coli (UPEC) we performed a drug-repurposing screen 6,454 approved drugs drug candidates. Using dilution-regrowth assays, identified 39 that either kill UPEC or delay its regrowth post-treatment. The hits include fluoroquinolones, macrolides, rifamycins, biguanide disinfectants, pleuromutilin, anti-cancer agents. 29 have not previously been recognized as were further tested Pseudomonas aeruginosa Staphylococcus aureus. Ten – solithromycin, rifabutin, mitomycin C, seven fluoroquinolones strong bactericidal activity P. aeruginosa, killing > 4 log10 bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, satraplatin unique in their ability selectively target bacteria, exhibiting poor efficacy growing Finally, 31 hit inhibit growth Shigella flexneri human enterocyte infection model, indicating permeate cytoplasm host cells. hold potential for treating infections, warranting comparative studies current standard-of-care antibiotics.

Language: Английский

Citations

0