Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 73, Issue 2, Pages 414-424Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkx395
Keywords
-
Funding
- European Union [634588, 245066]
- Danish Council For Independent Research (DFF) grant [11-106387]
- Danish National Research Foundation - Centre for Bacterial Stress Response and Persistence at the University of Copenhagen [DNFR 120]
- Laege Sofus Carl Emil Friis og hustru Olga Doris Friis' Legat
- Kirsten og Freddy Johansens Fond
- Juchum Foundation
Ask authors/readers for more resources
Objectives: To characterize NAI-107 and related lantibiotics for their in vitro activity against Gram-negative pathogens, alone or in combination with polymyxin, and against non-dividing cells or biofilms of Staphylococcus aureus. NAI-107 was also evaluated for its propensity to select or induce self-resistance in Gram-positive bacteria. Methods: We used MIC determinations and chequerboard experiments to establish the antibacterial activity of the examined compounds against target microorganisms. Time-kill assays were used to evaluate killing of exponential and stationary-phase cells. The effects on biofilms (growth inhibition and biofilm eradication) were evaluated using biofilm-coated pegs. The frequency of spontaneous resistantmutants was evaluated by either direct plating or by continuous sub-culturing at 0.5 x MIC levels, followed by population analysis profiles. Results: The results showed that NAI-107 and its brominated variant are highly active against Neisseria gonorrhoeae and some other fastidious Gram-negative pathogens. Furthermore, all compounds strongly synergized with polymyxin against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, and showed bactericidal activity. Surprisingly, NAI-107 alone was bactericidal against non-dividing A. baumannii cells. Against S. aureus, NAI-107 and related lantibiotics showed strong bactericidal activity against dividing and non-dividing cells. Activity was also observed against S. aureus biofilms. As expected for a lipid II binder, no significant resistance to NAI-107 was observed by direct plating or serial passages. Conclusions: Overall, the results of the current work, along with previously published results on the efficacy of NAI-107 in experimental models of infection, indicate that this lantibiotic represents a promising option in addressing the serious threat of antibiotic resistance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available