Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 13, Pages -Publisher
MDPI
DOI: 10.3390/ijms22136762
Keywords
metallacarboranes; Pseudomonas aeruginosa; Yersinia enterocolitica; antibacterials; resistance generation; boron clusters; COSAN
Funding
- National Science Centre, Poland [2016/23/D/NZ1/02611, 2016/21/B/NZ6/02028]
- Statutory Fund of Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
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Novel compounds based on metallacarborane cage showed antibacterial activity against Yersinia pestis substitute Yersinia enterocolitica and Pseudomonas aeruginosa, indicating a common mechanism for drug resistance in the former. The compounds had predominantly bacteriostatic effect and may serve as a starting point for novel anti-Yersinia drugs.
Pseudomonas aeruginosa is an opportunistic human pathogen that has become a nosocomial health problem worldwide. The pathogen has multiple drug removal and virulence secretion systems, is resistant to many antibiotics, and there is no commercial vaccine against it. Yersinia pestis is a zoonotic pathogen that is on the Select Agents list. The bacterium is the deadliest pathogen known to humans and antibiotic-resistant strains are appearing naturally. There is no commercial vaccine against the pathogen, either. In the current work, novel compounds based on metallacarborane cage were studied on strains of Pseudomonas aeruginosa and a Yersinia pestis substitute, Yersinia enterocolitica. The representative compounds had IC50 values below 10 mu M against Y. enterocolitica and values of 20-50 mu M against P. aeruginosa. Artificial generation of compound-resistant Y. enterocolitica suggested a common mechanism for drug resistance, the first reported in the literature, and suggested N-linked metallacarboranes as impervious to cellular mechanisms of resistance generation. SEM analysis of the compound-resistant strains showed that the compounds had a predominantly bacteriostatic effect and blocked bacterial cell division in Y. enterocolitica. The compounds could be a starting point towards novel anti-Yersinia drugs and the strategy presented here proposes a mechanism to bypass any future drug resistance in bacteria.
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