Reactive oxygen species induce DNA strand breaks and DNA oxidation. DNA oxidation leads to DNA mismatches, resulting
in mutations in the genome if not properly repaired. Homologous recombination (HR) and non-homologous end-joining
(NHEJ) are required for DNA strand breaks, whereas the base excision repair system mainly repairs oxidized DNAs, such as
8-oxoguanine and thymine glycol, by cleaving the glycosidic bond, inserting correct nucleotides, and sealing the gap. Our
previous studies revealed that the Rad53-Bdr1 pathway mainly controls DNA strand breaks through the regulation of HRand
NHEJ-related genes. However, the functional roles of genes involved in the base excision repair system remain elusive
in Cryptococcus neoformans. In the present study, we identified OGG1 and NTG1 genes in the base excision repair system
of C. neoformans, which are involved in DNA oxidation repair. The expression of OGG1 was induced in a Hog1-dependent
manner under oxidative stress. On the other hand, the expression of NTG1 was strongly induced by DNA damage stress in a
Rad53-independent manner. We demonstrated that the deletion of NTG1, but not OGG1, resulted in elevated susceptibility
to DNA damage agents and oxidative stress inducers. Notably, the ntg1Δ mutant showed growth defects upon antifungal
drug treatment. Although deletion of OGG1 or NTG1 did not increase mutation rates, the mutation profile of each ogg1Δ
and ntg1Δ mutant was different from that of the wild-type strain. Taken together, we found that DNA N-glycosylase Ntg1
is required for oxidative DNA damage stress and antifungal drug resistance in C. neoformans.
Apical periodontitis is caused by biofilm-mediated root canal
infection. Early phase oral bacterial biofilms are inhibited by
Lactobacillus plantarum lipoteichoic acid (Lp.LTA). However,
mature biofilms that develop over 3 weeks are more resistant
to traditional endodontic medicaments. Therefore, this study
examined the effectiveness of Lp.LTA on disrupting mature
Enterococcus faecalis biofilms, and on enhancing the effects
of endodontic medicaments. LTA was purified from L. plantarum
through butanol extraction followed by hydrophobic
and ion-exchange chromatography. E. faecalis biofilms were
formed over 3 weeks on glass bottom dishes and in dentin
blocks obtained from human single-rooted premolars. These
mature biofilms were treated with or without Lp.LTA for 1 h,
followed by additional treatment with either chlorhexidine
digluconate (CHX), calcium hydroxide (CH), or triple antibiotics
for 24 h. Biofilms on glass were live/dead stained and
quantified by ZEN through confocal laser microscopy. Biofilms
in dentin were fixed, sputter coated and analyzed by
ImageJ with scanning electron microscopy. Preformed E. faecalis
mature biofilms on the culture dishes were dose-dependently
disrupted by Lp.LTA. Lp.LTA potentiated the effects
of CHX or CH on the disruption of mature biofilm. Interestingly,
CHX-induced disruption of preformed E. faecalis
mature biofilms was synergistically enhanced only when pretreated
with Lp.LTA. Furthermore, in the dentin block model,
Lp.LTA alone reduced E. faecalis mature biofilm and
pre-treatment with Lp.LTA promoted the anti-biofilm activity
of CHX. Lp.LTA could be an anti-biofilm or supplementary
agent that can be effective for E. faecalis-biofilminduced
diseases.
Citations
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A Systematic Review of the Comparative Efficacy of Lactobacillus Probiotics and Sodium Hypochlorite as Intracanal Irrigants Against Enterococcus faecalis Mrinalini Mrinalini, Alpa Gupta, Dax Abraham, Arun Kumar Duraisamy, Rajat Sharma Cureus.2024;[Epub] CrossRef
The role of
Lactobacillus plantarum
in oral health: a review of current studies
Xinyan Huang, Jianhang Bao, Mingzhen Yang, Yingying Li, Youwen Liu, Yuankun Zhai Journal of Oral Microbiology.2024;[Epub] CrossRef
Lipoteichoic Acid from Lacticaseibacillus rhamnosus GG as a Novel Intracanal Medicament Targeting Enterococcus faecalis Biofilm Formation Ji-Young Yoon, Somin Park, Dongwook Lee, Ok-Jin Park, WooCheol Lee, Seung Hyun Han Journal of Microbiology.2024; 62(10): 897. CrossRef
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Plantaricin LD1 purified from Lactobacillus plantarum LD1 inhibits biofilm formation of Enterococcus faecalis ATCC 29212 in tooth model M.K. Yadav, P. Yadav, M. Dhiman, S. Tewari, S.K. Tiwari Letters in Applied Microbiology.2022; 75(3): 623. CrossRef
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Enterococcus faecalis, a Gram-positive bacterium commonly
isolated in patients with refractory apical periodontitis, invades
dentin tubules easily and forms biofilms. Bacteria in biofilms,
which contribute to recurrent and/or chronic inflammatory
diseases, are more resistant to antimicrobial agents
than planktonic cells and easily avoid phagocytosis. Although
Lactobacillus plantarum lipoteichoic acid (Lp.LTA) is associated
with biofilm formation, the effect of Lp.LTA on biofilm
formation by E. faecalis is not clearly understood. In this
study, we investigated whether Lp.LTA inhibits E. faecalis
biofilm formation. The degree of biofilm formation was determined
by using crystal violet assay and LIVE/DEAD bacteria
staining. The quantification of bacterial growth was determined
by measuring the optical density at 600 nm with a
spectrophotometer. Formation of biofilms on human dentin
slices was observed under a scanning electron microscope.
E. faecalis biofilm formation was reduced by Lp.LTA treatment
in a dose-dependent manner. Lp.LTA inhibited biofilm
development of E. faecalis at the early stage without affecting
bacterial growth. LTA from other Lactobacillus species
such as Lactobacillus acidophilus, Lactobacillus casei, or
Lactobacillus rhamnosus GG also inhibited E. faecalis biofilm
formation. In particular, among LTAs from various lactobacilli,
Lp.LTA showed the highest inhibitory effect on biofilms
formed by E. faecalis. Interestingly, LTAs from lactobacilli
could remove the biofilm preformed by E. faecalis.
These inhibitory effects were also observed on the surface of human dentin slices. In conclusion, Lactobacillus species LTA
inhibits biofilm formation caused by E. faecalis and it could
be used as an anti-biofilm agent for prevention or treatment
against E. faecalis-associated diseases.
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