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1.
BMC Genomics ; 25(1): 261, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38454321

ABSTRACT

Enterococcus faecalis, a formidable nosocomial and community-acquired opportunistic pathogen, can persist a wide range of extreme environments, including low pH and nutrient deficiency. Clarifying the survival mechanism of E. faecalis in low-pH conditions is the key to combating the infectious diseases caused by E. faecalis. In this study, we combined transcriptome profiling (RNA-seq) and transposon insertion sequencing (TIS) to comprehensively understand the genes that confer these features on E. faecalis. The metadata showed that genes whose products are involved in cation transportation and amino acid biosynthesis were predominantly differentially expressed under acid conditions. The products of genes such as opp1C and copY reduced the hydrion concentration in the cell, whereas those of gldA2, gnd2, ubiD, and ubiD2 mainly participated in amino metabolism, increasing matters to neutralize excess acid. These, together with the folE and hexB genes, which are involved in mismatch repair, form a network of E. faecalis genes necessary for its survival under acid conditions.


IMPORTANCE: As a serious nosocomial pathogen, Enterococcus faecalis was considered responsible for large numbers of infections. Its ability to survive under stress conditions, such as acid condition and nutrient deficiency was indispensable for its growth and infection. Therefore, understanding how E. faecalis survives acid stress is necessary for the prevention and treatment of related diseases. RNA-seq and TIS provide us a way to analyze the changes in gene expression under such conditions.


Subject(s)
Enterococcus faecalis , Gene Expression Profiling , RNA-Seq , Enterococcus faecalis/genetics , Genome
2.
Adv Healthc Mater ; 13(14): e2303740, 2024 06.
Article in English | MEDLINE | ID: mdl-38413194

ABSTRACT

Avascular dense connective tissues (e.g., the annulus fibrosus (AF) rupture, the meniscus tear, and tendons and ligaments injury) repair remains a challenge due to the "biological barrier" that hinders traditional drug permeation and limits self-healing of the injured tissue. Here, accurate delivery of nitric oxide (NO) to penetrate the "AF biological barrier" is achieved thereby enabling programmable AF repair. NO-loaded BioMOFs are synthesized and mixed in a modified polyvinyl alcohol and PCL-composited electrospun fiber membrane with excellent reactive oxygen species-responsive capability (LN@PM). The results show that LN@PM could respond to the high oxidative stress environment at the injured tissue and realize continuous and substantial NO release. Based on low molecular weight and lipophilicity, NO could penetrate through the "biological barrier" for accurate AF drug delivery. Moreover, the dynamic characteristics of the LN@PM reaction can be matched with the pathological microenvironment to initiate programmable tissue repair including sequential remodeling microenvironment, reprogramming the immune environment, and finally promoting tissue regeneration. This tailored programmable treatment strategy that matches the pathological repair process significantly repairs AF, ultimately alleviating intervertebral disc degeneration. This study highlights a promising approach for avascular dense connective tissue treatment through intelligent NO release, effectively overcoming "AF biological barriers" and programmable treatment.


Subject(s)
Nitric Oxide , Nitric Oxide/metabolism , Animals , Annulus Fibrosus/drug effects , Drug Delivery Systems/methods , Connective Tissue , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Polyvinyl Alcohol/chemistry , Intervertebral Disc Degeneration/metabolism , Male , Rats , Mice , Rabbits
3.
Front Cell Infect Microbiol ; 13: 1157368, 2023.
Article in English | MEDLINE | ID: mdl-37180439

ABSTRACT

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a phenotype of liver diseases associated with metabolic syndrome. The pathogenesis MAFLD remains unclear. The liver maintains is located near the intestine and is physiologically interdependent with the intestine via metabolic exchange and microbial transmission, underpinning the recently proposed "oral-gut-liver axis" concept. However, little is known about the roles of commensal fungi in the disease development. This study aimed to characterize the alterations of oral and gut mycobiota and their roles in MAFLD. Twenty-one MAFLD participants and 20 healthy controls were enrolled. Metagenomics analyses of saliva, supragingival plaques, and feces revealed significant alterations in the gut fungal composition of MAFLD patients. Although no statistical difference was evident in the oral mycobiome diversity within MAFLD and healthy group, significantly decreased diversities were observed in fecal samples of MAFLD patients. The relative abundance of one salivary species, five supragingival species, and seven fecal species was significantly altered in MAFLD patients. Twenty-two salivary, 23 supragingival, and 22 fecal species were associated with clinical parameters. Concerning the different functions of fungal species, pathways involved in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and carbon metabolism were abundant both in the oral and gut mycobiomes. Moreover, different fungal contributions in core functions were observed between MAFLD patients and the healthy controls, especially in the supragingival plaque and fecal samples. Finally, correlation analysis between oral/gut mycobiome and clinical parameters identified correlations of certain fungal species in both oral and gut niches. Particularly, Mucor ambiguus, which was abundant both in saliva and feces, was positively correlated with body mass index, total cholesterol, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase, providing evidence of a possible "oral-gut-liver" axis. The findings illustrate the potential correlation between core mycobiome and the development of MAFLD and could propose potential therapeutic strategies.


Subject(s)
Gastrointestinal Microbiome , Mycobiome , Non-alcoholic Fatty Liver Disease , Humans , Fungi/genetics , Feces/microbiology , Saliva
4.
J Oral Microbiol ; 13(1): 1860398, 2020 Dec 24.
Article in English | MEDLINE | ID: mdl-33456722

ABSTRACT

Bacteriophage T4 RNA ligase 1 (T4 Rnl1) can be stably expressed in many bacteria and has been reported to affect the bioactivity of the host bacteria. Recently, we constructed bacteriophage T4 Rnl1 expressing system in Streptococcus mutans, a crucial biofilm-forming and dental caries-causing oral pathogen. Here, we characterized the function of recombinant bacteriophage T4 Rnl1 in biofilm formation of S. mutans. The T4 Rnl1 mutant exhibited similar growth phenotype but resulted in a significant reduction of biofilm biomass compared to wild type strain and empty plasmid carrying strain. The abnormal biofilm of the T4 Rnl1 mutant harbored loose bacterial clusters with defective production and distribution of exopolysaccharides. Moreover, the expression of several biofilm formation-associated genes was dysregulated at mRNA level in the T4 Rnl1 mutant. These results reveal that the bacteriophage T4 Rnl1 exert antibiofilm activities against the cariogenic bacterium S. mutans, which impacts the spatial organization of the exopolysaccharides and further impairs the three-dimensional biofilm architecture. These findings implicate that manipulation of bacteriophage T4 Rnl1, a biological tool used for RNA ligation, will provide a promising approach to cariogenic biofilm control.

5.
ACS Appl Mater Interfaces ; 12(7): 8915-8928, 2020 Feb 19.
Article in English | MEDLINE | ID: mdl-31971763

ABSTRACT

Microbial disinfection associated with medical device surfaces has been an increasing need, and surface modification strategies such as antibacterial coatings have gained great interest. Here, we report the development of polydopamine-ferrocene (PDA-Fc)-functionalized TiO2 nanorods (Ti-Nd-PDA-Fc) as a context-dependent antibacterial system on implant to combat bacterial infection and hinder biofilm formation. In this work, two synergistic antimicrobial mechanisms of the PDA-Fc coating are proposed. First, the PDA-Fc coating is redox-active and can be locally activated to release antibacterial reactive oxygen species (ROS), especially ·OH in response to the acidic microenvironment induced by bacteria colonization and host immune responses. The results demonstrate that redox-based antimicrobial activity of Ti-Nd-PDA-Fc offers antibacterial efficacy of over 95 and 92% against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), respectively. Second, the photothermal effect of PDA can enhance the antibacterial capability upon near-infrared (NIR) irradiation, with over 99% killing efficacy against MRSA and E. coli, and even suppress the formation of biofilm through both localized hyperthermia and enhanced ·OH generation. Additionally, Ti-Nd-PDA-Fc is biocompatible when tested with model pre-osteoblast MC-3T3 E1 cells and promotes cell adhesion and spreading presumably due to its nanotopographical features. The MRSA-infected wound model also indicates that Ti-Nd-PDA-Fc with NIR irradiation can effectively eliminate bacterial infection and suppress host inflammatory responses. We believe that this study demonstrates a simple means to create biocompatible redox-active coatings that confer context-dependent antibacterial activities to implant surfaces.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Coated Materials, Biocompatible/pharmacology , Ferrous Compounds/pharmacology , Indoles/pharmacology , Metallocenes/pharmacology , Nanotubes/chemistry , Polymers/pharmacology , Prostheses and Implants , 3T3 Cells , Animals , Escherichia coli/drug effects , Ferrous Compounds/chemistry , Indoles/chemistry , Male , Metallocenes/chemistry , Mice , Microbial Sensitivity Tests , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanotubes/ultrastructure , Oxidation-Reduction , Phototherapy , Polymers/chemistry , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/pharmacology , Staphylococcus aureus/drug effects , Temperature , Titanium/chemistry , Titanium/pharmacology , Wound Healing/drug effects , X-Ray Diffraction
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