J Microbiol Biotechnol
November 2024
Int J Syst Evol Microbiol
August 2024
A novel, Gram-positive, facultatively anaerobic, and non-motile bacterial strain, designated B2T-5, was isolated from jeotgal, a traditional Korean fermented seafood. Colonies grown on gifu anaerobic medium agar plates were cream-coloured, irregular, and umbonate with curled margins. Optimal growth of strain B2T-5 occurred at 20 °C, pH 8.
View Article and Find Full Text PDFImmunotherapy has revolutionized the treatment of cancer but continues to be constrained by limited response rates, acquired resistance, toxicities and high costs, which necessitates the development of new, innovative strategies. The discovery of a connection between the human microbiota and cancer dates back 4,000 years, when local infection was observed to result in tumour eradication in some individuals. However, the true oncological relevance of the intratumoural microbiota was not recognized until the turn of the twentieth century.
View Article and Find Full Text PDFPurpose: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe.
View Article and Find Full Text PDFCancer Genomics Proteomics
April 2024
Background/aim: Colorectal cancer (CRC) is the third most common cancer worldwide, and is second only to lung cancer with respect to cancer-related deaths. Noninvasive molecular imaging using established markers is a new emerging method to diagnose CRC. The human ephrin receptor family type-A 2 (hEPHA2) oncoprotein is overexpressed at the early, but not late, stages of CRC.
View Article and Find Full Text PDFRadiotherapy (RT) triggers immunogenic cell death (ICD). L-ASNase, which catalyzes the conversion of asparagine (Asn), thereby depleting it, is used in the treatment of blood cancers. In previous work, we showed that CRT3LP and CRT4LP, PASylated L-ASNases conjugated to the calreticulin (CRT)-specific monobodies CRT3 and CRT4, increase the efficacy of ICD-inducing chemotherapy.
View Article and Find Full Text PDFPurpose: Attenuated Salmonella typhimurium is a potential biotherapeutic antitumor agent because it can colonize tumors and inhibit their growth. The present study aimed to develop a doxycycline (Doxy)-inducible gene switch system in attenuated S. typhimurium and assess its therapeutic efficacy in various tumor-bearing mice models.
View Article and Find Full Text PDFA series of Yb-substituted Zintl phases in the CaYbAlSb (0 ≤ ≤ 0.81(1)) system has been synthesized by initial arc melting and post-heat treatment, and their isotypic crystal structures were characterized by both powder and single crystal X-ray diffraction analysis. All four title compounds adopted the CaAlAs-type structure (space group , Pearson code 28, = 4).
View Article and Find Full Text PDFHere, we provide a brief overview of the approaches and strategies underlying bacteria-based cancer immunotherapy (BCiT). We also describe and summarize research in the field of synthetic biology, which aims to regulate bacterial growth and gene expression for immunotherapeutic use. Finally, we discuss the current clinical status and limitations of BCiT.
View Article and Find Full Text PDFThe use of appropriately designed immunotherapeutic bacteria is an appealing approach to tumor therapy because the bacteria specifically target tumor tissue and deliver therapeutic payloads. The present study describes the engineering of an attenuated strain of Salmonella typhimurium deficient in ppGpp biosynthesis (SAM) that could secrete Vibrio vulnificus flagellin B (FlaB) conjugated to human (hIL15/FlaB) and mouse (mIL15/FlaB) interleukin-15 proteins in the presence of L-arabinose (L-ara). These strains, named SAMphIF and SAMpmIF, respectively, secreted fusion proteins that retained bioactivity of both FlaB and IL15.
View Article and Find Full Text PDFL-Asparaginase (L-ASNase), a bacterial enzyme that degrades asparagine, has been commonly used in combination with several chemical drugs to treat malignant hematopoietic cancers such as acute lymphoblastic leukemia (ALL). In contrast, the enzyme was known to inhibit the growth of solid tumor cells in vitro, but not to be effective in vivo. We previously reported that two novel monobodies (CRT3 and CRT4) bound specifically with calreticulin (CRT) exposed on tumor cells and tissues during immunogenic cell death (ICD).
View Article and Find Full Text PDFBiosensors (Basel)
February 2023
Recent progress in synthetic biology has enabled bacteria to respond to specific disease signals to perform diagnostic and/or therapeutic tasks. subsp. serovar Typhimurium ( Typhimurium) colonization of tumors results in increases in nitric oxide (NO) levels, suggesting that NO may act as a candidate inducer of tumor-specific gene expression.
View Article and Find Full Text PDFA novel, strictly anaerobic, gram-negative, segmented filamentous bacterium strain AGMB03513, was isolated from the faeces of a 5-month-old pig. Phylogenetic analysis based on the 16S rRNA gene indicated that the isolate was a member of the family Lachnospiraceae, and the closest strain was Anaerostipes butyraticus. Strain AGMB03513 formed a lineage within the genus Anaerostipes and was closely related to A.
View Article and Find Full Text PDFPurpose: In the programming of tumor-targeting bacteria, various therapeutic or reporter genes are expressed by different gene-triggering strategies. Previously, we engineered pJL87 plasmid with an inducible bacterial drug delivery system that simultaneously co-expressed two genes for therapy and imaging by a bidirectional tet promoter system only in response to the administration of exogenous doxycycline (Doxy). In this multi-cassette expression approach, tetA promoter (P) was 100-fold higher in expression strength than tetR promoter (P).
View Article and Find Full Text PDFPancreatic cancer is resistant to conventional therapeutic interventions, mainly due to abundant cancer stromal cells and poor immune cell infiltration. Here, we used a targeted cancer therapy approach based on attenuated Salmonella typhimurium engineered to express cytolysin A (ClyA) to target cancer stromal cells and cancer cells and treat pancreatic cancer in mice. Nude mice bearing subcutaneous or orthotopic human pancreatic cancers were treated with engineered S.
View Article and Find Full Text PDFSurface-exposed calreticulin (ecto-CRT) plays a crucial role in the phagocytic removal of apoptotic cells during immunotherapy. Ecto-CRT is an immunogenic signal induced in response to treatment with chemotherapeutic agents such as doxorubicin (DOX) and mitoxantrone (MTX), and two peptides (KLGFFKR (Integrin-α) and GQPMYGQPMY (CRT binding peptide 1, Hep-I)) are known to specifically bind CRT. To engineer CRT-specific monobodies as agents to detect immunogenic cell death (ICD), we fused these peptide sequences at the binding loops (BC and FG) of human fibronectin domain III (FN3).
View Article and Find Full Text PDFSurface-exposed calreticulin (ecto-CRT) is a well-known "eat-me" signal exhibited by dying cells that contributes to their recognition and destruction by the immune system. We assessed the use of a CRT-specific binding peptide for imaging ecto-CRT during immunogenic cell death and its utility for early prediction of treatment response. A synthetic CRT-specific peptide, KLGFFKR (CRTpep), was labeled with fluorescein isothiocyanate or F, and the characteristics of ecto-CRT were evaluated in a colon cancer cell line in vitro and in vivo.
View Article and Find Full Text PDFWe previously reported on the monobody E1, which specifically targets the tumor marker hEphA2. In this study, we labeled NOTA-conjugated E1 with Cu (Cu-NOTA-E1) and evaluated biologic characteristics. The uptake of Cu-NOTA-E1 in PC3 cells (a human prostate cancer cell line) with high expression of hEphA2 increased in a time-dependent manner.
View Article and Find Full Text PDFTumor-targeting bacteria have been actively investigated as a new therapeutic tool for solid tumors. However, imaging of tumor-targeting bacteria has not been fully established. F-fluorodeoxysorbitol (FDS) positron emission tomography (PET) is known to be capable of imaging Gram-negative Enterobacteriaceae infection.
View Article and Find Full Text PDFserovar Typhimurium is one of the most important bacterial pathogens causing diarrhea. The resistance of to antimicrobial agents, which has recently been isolated from patients, is causing serious problems. We investigated the effects of salicylic acid (Sal) and acetyl salicylate (AcSal) on the susceptibility of to cephalosporin antibiotics, which are known to increase resistance to cephalosporin and quinolone antibiotics.
View Article and Find Full Text PDFProgressive cerebellar ataxias are rare diseases during childhood, especially under 6 years of age. In a single family, three affected siblings exhibited Friedreich's-ataxia-like phenotypes before 2 years of age. They had progressive cerebellar atrophy, intellectual disability, and scoliosis.
View Article and Find Full Text PDFThe accurate detection of disease-related biomarkers is crucial for the early diagnosis and management of disease in personalized medicine. Here, we present a molecular imaging of human epidermal growth factor receptor (EGFR)-expressing malignant tumors using an EGFR-specific repebody composed of leucine-rich repeat (LRR) modules. The repebody was labeled with either a fluorescent dye or radioisotope, and used for imaging of EGFR-expressing malignant tumors using an optical method and positron emission tomography.
View Article and Find Full Text PDFIn a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E.
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