From fragments to leads: novel bacterial NAD + -dependent DNA ligase inhibitors

Hale, Michael R.; Brassington, C.; Carcanague, D.; Embrey, Kevin J.; Eyermann, Charles J.; Giacobbe, Robert A.; Gingipalli, Lakshmaiah; Gowravaram, Madhusudhan; Harang, Jenna; Howard, Tina D.; Ioannidis, Georgine; Jahić, Haris; Kutschke, Amy; Laganas, Valerie A.; Loch, James T.; Miller, M.D.; Murphy-Benenato, Kerry E.; Oguto, Herbert; Otterbein, Ludovic R.; Patel, Sahil Joe; Shapiro, Adam B.; Boriack-Sjodin, P.A.

doi:10.1016/j.tetlet.2014.12.067

Cited by 8 publications

(3 citation statements)

References 23 publications

(6 reference statements)

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“…In the present study, we observed an increase in the number of proteins with DNA repair functions in the E. faecalis mutant (Table 2), suggesting that the integrity of the bacterial DNA might be compromised. These proteins include the NAD-dependent DNA ligase, which has the function of rejoining the ends of the DNA during single-stranded or double-stranded DNA breaks (Hale et al, 2015), the RecA protein involved in homologous recombination and the repair of DNA double-strand breaks (Tham et al, 2016), the RecJ exonuclease which participates in homologous recombination and mismatch repair (Han et al, 2006), and MutS, MutS2 and MutL involved in mismatch repair (Eisen, 1998).…”

Section: Dna Damagementioning

confidence: 99%

Proteomic analysis of an Enterococcus faecalis mutant generated against the exposure to silver nanoparticles

Orozco

Niño-Martínez

Martínez-Castañón

et al. 2021

J of Applied Microbiology

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Introduction Nanoparticles (NPs) have been widely studied as an alternative to antibiotic use due to their antimicrobial properties at lower concentrations. Enterococcus faecalis is a facultative Gram‐positive microorganism inhabiting the gastrointestinal tract of humans and animals. It can also be present in other environments such as the oral cavity, water, sewage, soil and food. Aims We evaluated whether E. faecalis could develop resistance to silver NPs (AgNPs) after exposure to sublethal concentrations of the NPs. Methods and Results Proteomic analyses revealed that different pathways were activated during the acquired resistance under sublethal concentrations, and selected genes were validated by qPCR. Conclusions The results of this study showed that E. faecalis is capable of generating resistance to AgNPs. Significance and Impact of the Study To avoid the generation of resistance against AgNPs, future use of these NPs should be combined with other NPs prepared with different metals to prevent the dissemination of resistant strains.

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Section: Dna Damagementioning

confidence: 99%

Proteomic analysis of an Enterococcus faecalis mutant generated against the exposure to silver nanoparticles

Orozco

Niño-Martínez

Martínez-Castañón

et al. 2021

J of Applied Microbiology

View full text Add to dashboard Cite

show abstract

“…In addition, we go on to highlight modifications of co-factors that alter the biochemical activities of these important enzymes, with a particular focus on altered forms of β-nicotinamide adenine dinucleotide (β-NAD + ). Recent developments in identifying such compounds as selective inhibitors of a range of NAD + -dependent enzymes is encouraging for their development as potential drug candidates [ 8 , 11 , 12 ].…”

Section: Dna Ligasesmentioning

confidence: 99%

“…Detailed characterization of DNA ligases at a biochemical and molecular level has generated therapeutic interest, with the essential NDLs of bacteria being a suggested target for novel antibiotics candidates [ 2 , 7 , 8 , 11 , 12 ]. The starting point for many studies that aim to inhibit such enzymes is to assess the effects of modified derivatives of the co-factors, either β-NAD + or ATP in the case of DNA ligases.…”

Section: Inhibitors and Non-natural Substrates Of Dna Ligasesmentioning

confidence: 99%