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Article

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

Institute of Biochemistry and Biophysics, Polish Academy of Sciences (IBB PAS), Pawińskiego 5a, 02-106 Warsaw, Poland
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Academic Editor: Ismail Fliss
Int. J. Mol. Sci. 2021, 22(3), 1014; https://doi.org/10.3390/ijms22031014
Received: 31 December 2020 / Revised: 18 January 2021 / Accepted: 18 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue Antibiotic Resistance: Appearance, Evolution, and Spread)
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 antimicrobial peptides that target cytoplasmic membrane is an especially promising strategy since essential functions and the conserved structure of the membrane hinder the development of bacterial resistance. Aureocin A53- and enterocin L50-like bacteriocins are highly cationic, membrane-targeting antimicrobial peptides that have potential as next-generation antibiotics. However, 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 Lactococcus 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 underwent susceptibility tests with a wide array of bacteriocins and antibiotics. The highest alterations 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 (bacitracin). Interestingly, decreased via the SNPs accumulation sensitivity to membrane-active bacteriocins and antibiotics resulted in the concurrently increased vulnerability to bacitracin, carbenicillin, 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 overexpression of dxsA restored the phenotype observed in spontaneous mutants. View Full-Text
Keywords: aureocin A53- and enterocin L50-like bacteriocins; nisin; lactococcin 972; cell envelope-acting antibiotics; bacteriocins and antibiotic resistance; lipid metabolism; Lactococcus lactis aureocin A53- and enterocin L50-like bacteriocins; nisin; lactococcin 972; cell envelope-acting antibiotics; bacteriocins and antibiotic resistance; lipid metabolism; Lactococcus lactis
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MDPI and ACS Style

Tymoszewska, A.; Aleksandrzak-Piekarczyk, T. The Lactococcal dgkB (yecE) and dxsA Genes for Lipid Metabolism Are Involved in the Resistance to Cell Envelope-Acting Antimicrobials. Int. J. Mol. Sci. 2021, 22, 1014. https://doi.org/10.3390/ijms22031014

AMA Style

Tymoszewska A, Aleksandrzak-Piekarczyk T. 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. 2021; 22(3):1014. https://doi.org/10.3390/ijms22031014

Chicago/Turabian Style

Tymoszewska, Aleksandra, and Tamara Aleksandrzak-Piekarczyk. 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, no. 3: 1014. https://doi.org/10.3390/ijms22031014

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