Background: Since recognizing the interaction between Brucella and host cells is crucial to the elucidation of the infectious process, Brucella researches have prioritized the investigation of genes related to pathogenicity. To demonstrate the roles of Brucella genes, RAW 264.7 cells were infected with the Brucella abortus wild-type and mutant strains (generated using transposon mutagenesis), after which the different transcriptional responses of the infected cells were determined using microarray.
Results: Following infection, enhanced strategies for intracellular survival, such as down-regulation of genes associated with cytokine responses and apoptosis, were observed in RAW 264.7 cells infected with C3 mutant strain when compared to the transcriptional responses of wild-type infected cells. Using sequence analysis, we determined the mutation site of a C3 mutant strain as the ATP-binding cassette transporter permease (BruAb2_1031). These results were evidenced by an increased level of intracellular survival of the C3 mutant strain.
Conclusions: Characteristics of each mutant strain including bacterial growth rate, abilities to induce cytokine production in macrophages after infection, internalization, and levels of intracellular survival and replication, were investigated by performing RAW 264.7 cell infection experiments. Our results indicate that the BruAb2_1031 gene might be closely related with intracellular survival of B. abortus in RAW 264.7 cells.
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http://dx.doi.org/10.1186/s12866-018-1223-7 | DOI Listing |
( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.
View Article and Find Full Text PDFPaxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. PXN interacts directly with the C-terminal targeting domain of FAK (FAT) via its intrinsically disordered N-terminal domain. This interaction is necessary and sufficient for localizing FAK to focal adhesions.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.
Background: Cancer treatments are still limited by various challenges, such as off-target drug delivery, posttreatment inflammation, and the hypoxic conditions in the tumor microenvironment; thus, the development of effective therapeutics remains highly desirable. Exosomes are extracellular vesicles with a size of 30-200 nm that have been widely applied as drug carriers over the last decade. In this study, melanoma-derived exosomes were used to develop a perfluorocarbon (PFC) drug nanocarriers loaded with indocyanine green (ICG) and camptothecin (CPT) (ICFESs) for targeted cancer photochemotherapy.
View Article and Find Full Text PDFTransplant Direct
February 2025
Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.
Background: Alloprimed antibody-suppressor CXCR5CD8 T cells (CD8 T cells) downregulate alloantibody production, mediate cytotoxicity of IgG B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8 T cell-mediated cytotoxicity or noncytotoxic suppression.
Methods: Alloprimed immune-cell subsets were evaluated for susceptibility to CD8 T cell-mediated in vitro cytotoxicity and/or suppression of intracellular cytokine expression.
Persisters describe phenotypically switched cells refractory to antibiotic killing in a genetically susceptible population, while preserving the ability to resume growth when antibiotics are discontinued1,2. Since its proposal 70 years ago, great strides were made to build the framework regarding persistence, including defining triggered, spontaneous and antibiotic-induced persisters. However, challenges remain in characterizing the molecular determinants underlying the phenotypic switch into persistence3.
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