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The Lactococcal dgkB (yecE) and dxsA Genes for Lipid Metabolism Are Involved in the Resistance to Cell Envelope-Acting Antimicrobials

Tymoszewska, Aleksandra and Aleksandrzak-Piekarczyk, Tamara (2021) The Lactococcal dgkB (yecE) and dxsA Genes for Lipid Metabolism Are Involved in the Resistance to Cell Envelope-Acting Antimicrobials. International Journal of Molecular Sciences, 22 (3). p. 1014. ISSN 1422-0067


Official URL: http://doi.org/10.3390/ijms22031014


Abstract: The emergence of antibiotic-resistant bacteria led to an urgent need for next-generation antimicrobial agents with novel mechanisms of action. The use of positively charged antimicro-bial peptides that target cytoplasmic membrane is an especially promising strategy since essen-tial functions and the conserved structure of the membrane hinder the development of bacterial resistance. Aureocin A53- and enterocin L50-like bacteriocins are highly cationic, mem-brane-targeting antimicrobial peptides that have potential as next-generation antibiotics. How-ever, the mechanisms of resistance to these bacteriocins and cross-resistance against antibiotics must be examined before application to ensure their safe use. Here, in the model bacterium Lac-tococcus lactis, we studied the development of resistance to selected aureocin A53- and enterocin L50-like bacteriocins and its correlation with antibiotics. First, to generate spontaneous resistant mutants, L. lactis was exposed to bacteriocin BHT-B. Sequencing of their genomes revealed single nucleotide polymorphisms (SNPs) in the dgkB (yecE) and dxsA genes encoding diacylglycerol kinase and 1-deoxy-D-xylulose 5-phosphate synthase, respectively. Then, selected mutants un-derwent susceptibility tests with a wide array of bacteriocins and antibiotics. The highest altera-tions in the sensitivity of studied mutants were seen in the presence of cytoplasmic membrane targeting bacteriocins (K411, Ent7, EntL50, WelM, SalC, nisin) and antibiotics (daptomycin and gramicidin) as well as lipid II cycle-blocking bacteriocins (nisin and Lcn972) and antibiotics (bac-itracin). Interestingly, decreased via the SNPs accumulation sensitivity to membrane-active bac-teriocins and antibiotics resulted in the concurrently increased vulnerability to bacitracin, car-benicillin or chlortetracycline. It is suspected that SNPs may result in alterations to the efficiency of the nascent enzymes rather than a total loss of their function as neither deletion nor overex-pression of dxsA restored the phenotype observed in spontaneous mutants.

Item Type:Article
Subjects:Q Science > QR Microbiology
Divisions:Department of Microbial Biochemistry
ID Code:1984
Deposited By: dr Tamara Aleksandrzak-Piekarczyk
Deposited On:22 Jan 2021 08:25
Last Modified:22 Jan 2021 08:25

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