Antimicrobial resistance and the shortage of novel antibiotics have led to an urgent need for new antibacterial drug leads. Several existing natural product scaffolds (including chelocardins) have not been developed because their suboptimal pharmacological properties could not be addressed at the time. It is demonstrated here that reviving such compounds through the application of biosynthetic engineering can deliver novel drug candidates. In this paper, through a rational approach, the carboxyamido moiety of tetracyclines (an important structural feature for their bioactivity) was introduced into the chelocardins, which are atypical tetracyclines with an unknown mode of action. A broadspectrum antibiotic lead was generated with significantly improved activity, including against all Gram negative pathogens of the ESKAPE panel. Since the lead structure is also amenable to further chemical modification, it is a platform for further development through medicinal chemistry and genetic engineering. we published our results in a renowned journal with high impact factor.
COBISS.SI-ID: 4486520
Microorganisms are directly influenced by actions of their neighbours and cooperative behaviors are favored among relatives. Only a few microbial species are known to discriminate between kin and non-kin and distribution of this trait within sympatric bacterial populations is still poorly understood. We pubished our work in the eminent journal PNAS where we provide evidence of kin discrimination among micrometer scale soil isolates of Bacillus subtilis. This social mechanisms is reflected in striking boundaries between non-kin sympatric conspecifics during cooperative swarming on agar. Swarming incompatibilities were frequent and correlated with phylogenetic relatedness, as only the most related strains merged during swarming. Moreover, mixing of strains during colonization of a plant root suggested possible antagonism between non-kin. The work sheds light on kin discrimination on a model Gram (+) bacterium and opens up a new field of research addressing mechansims of this phenomen, its implications for social evolution and for development of novel probiotics and plant growth promoting biofertilisers that often contain Bacillus species. The work has been despite recent publication already cited 3 times and a positive commentary on the work appeared in PNAS.
COBISS.SI-ID: 4570488
The article in high ranking journal Nature Chemical Biology addresses novel finding in the metabolism of coenzyme A (CoA), which gained renewed attention recently because of its roles in neurodegeneration, protein acetylation, autophagy and signal transduction. The long-standing dogma was that eukaryotic cells obtain CoA exclusively via the uptake of extracellular precursors, especially vitamin B5. This study demonstrates an alternative mechanism that allows cells to obtain CoA by using exogenous CoA or its precursor 4’-phosphopantetheine, a biologically stable natural molecule able to translocate through cell membranes. Our findings were obtained in parallel with activities of a drug discovery program in the scope of the EU-FP7 project Tircon, which finalized successfully in 2015 and have major implications for the understanding of CoA-related diseases and therapies. Expertise of Acies Bio on (bio)synthetic pathways towards 4-phosphopantetheine was one of the key aspects of this collaborative and highly relevant research work.
COBISS.SI-ID: 4557944
The work, published in the top 5% journal (A") in the field of agriculture, brings results on kinetics of quorum sensing in Saccharomyces cerevisiae studied by using a mini-fermentation platform. The quorum sensing-molecules were monitored using our previous HPLC approach that is here supported by quantitative real-time PCR analysis of the quorum-sensing genes. We thus initially confirm correlations between peak production rates of the monitored quorum sensing-molecules 2-phenylethanol, tryptophol, and tyrosol and peak expression of the genes responsible for their synthesis: ARO8, ARO9 and ARO10. This confirms the accuracy of our previously implemented kinetic model, thus favoring its use in further studies in this field. We also show that the quorum-sensing kinetics are precisely dependent on the population growth phase, and that tyrosol production is also regulated by cell concentration, which has not been reported previously. Additionally, we show that during wine fermentation, ethanol stress reduces the production of 2-phenylethanol, tryptophol and tyrosol, which opens new challenges in the control of wine fermentation.
COBISS.SI-ID: 4561272
We investigated the mode of action of (-)-α-pinene in terms of its modulation of antibiotic resistance in Campylobacter jejuni. The target antimicrobial efflux systems were identified using an insertion mutagenesis approach, and C. jejuni adaptation to (-)-α-pinene was evaluated using DNA microarrays. We investigated adaptation of C. jejuni mutant strains to several stress factors, including osmolytes, and pH, using Biolog phenotypical microarrays. We confirmed that (-)-α-pinene efficiently modulates antibiotic resistance in C. jejuni by decreasing the minimum inhibitory concentrations of ciprofloxacin, erythromycin and triclosan by up to 512-fold. Furthermore, (-)-α-pinene promotes increased expression of cmeABC and another putative antimicrobial efflux gene, Cj1687. The ethidium bromide accumulation was greater in the wild-type strain than in the antimicrobial efflux mutant strains, which indicates that these antimicrobial efflux systems are a target of action of (-)-α-pinene.
COBISS.SI-ID: 4517752