scholarly journals Reporter gene-based optoacoustic imaging of E. coli targeted colon cancer in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Misun Yun ◽  
Sung-Hwan You ◽  
Vu Hong Nguyen ◽  
Jaya Prakash ◽  
Sarah Glasl ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Bacterial Colonization ◽  
Optoacoustic Imaging ◽  
E Coli ◽  
Non Invasive ◽  
Endogenous Contrast ◽  
Further Development ◽  
Engineered Bacteria ◽  
Cancer Targeted Therapy

AbstractBacteria-mediated cancer-targeted therapy is a novel experimental strategy for the treatment of cancers. Bacteria can be engineered to overcome a major challenge of existing therapeutics by differentiating between malignant and healthy tissue. A prerequisite for further development and study of engineered bacteria is a suitable imaging concept which allows bacterial visualization in tissue and monitoring bacterial targeting and proliferation. Optoacoustics (OA) is an evolving technology allowing whole-tumor imaging and thereby direct observation of bacterial colonization in tumor regions. However, bacterial detection using OA is currently hampered by the lack of endogenous contrast or suitable transgene fluorescent labels. Here, we demonstrate improved visualization of cancer-targeting bacteria using OA imaging and E. coli engineered to express tyrosinase, which uses L-tyrosine as the substrate to produce the strong optoacoustic probe melanin in the tumor microenvironment. Tumors of animals injected with tyrosinase-expressing E. coli showed strong melanin signals, allowing to resolve bacterial growth in the tumor over time using multispectral OA tomography (MSOT). MSOT imaging of melanin accumulation in tumors was confirmed by melanin and E. coli staining. Our results demonstrate that using tyrosinase-expressing E. coli enables non-invasive, longitudinal monitoring of bacterial targeting and proliferation in cancer using MSOT.

scholarly journals Reporter Gene-Based Optoacoustic Imaging of E. coli Targeted Colon Cancer In vivo

2021 ◽  
Author(s):  
Misun Yun ◽  
Sung-Hwan You ◽  
Vu Hong Nguyen ◽  
Jaya Prakash ◽  
Sarah Glasl ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Bacterial Colonization ◽  
Optoacoustic Imaging ◽  
E Coli ◽  
Non Invasive ◽  
Endogenous Contrast ◽  
Further Development ◽  
Engineered Bacteria ◽  
Cancer Targeted Therapy

Abstract Bacteria-mediated cancer-targeted therapy is a novel experimental strategy for the treatment of cancers. Bacteria can be engineered to overcome a major challenge of existing therapeutics by differentiating between malignant and healthy tissue. A prerequisite for further development and study of engineered bacteria is a suitable imaging concept which allows bacterial visualization in tissue and monitoring bacterial targeting and proliferation. Optoacoustics (OA) is an evolving technology allowing whole-tumor imaging and thereby direct observation of bacterial colonization in tumor regions. However, bacterial detection using OA is currently hampered by the lack of endogenous contrast or suitable transgene fluorescent labels. Here, we demonstrate improved visualization of cancer-targeting bacteria using OA imaging and E. coli engineered to express tyrosinase, which uses L-tyrosine as the substrate to produce the strong optoacoustic probe melanin in the tumor microenvironment. Tumors of animals injected with tyrosinase-expressing E. coli showed strong melanin signals, allowing to resolve bacterial growth in the tumor over time using multispectral OA tomography (MSOT). MSOT imaging of melanin accumulation in tumors was confirmed by melanin and E. coli staining. Our results demonstrate that using tyrosinase-expressing E. coli enables non-invasive, longitudinal monitoring of bacterial targeting and proliferation in cancer using MSOT.

scholarly journals Giardia duodenalis-induced alterations of commensal bacteria killCaenorhabditis elegans: a new model to study microbial-microbial interactions in the gut

2015 ◽  
Vol 308 (6) ◽  
pp. G550-G561 ◽  
Author(s):  
Teklu K. Gerbaba ◽  
Pratyush Gupta ◽  
Kevin Rioux ◽  
Dave Hansen ◽  
Andre G. Buret
Keyword(s):  
Bacterial Colonization ◽  
Giardia Duodenalis ◽  
Microbial Interactions ◽  
Commensal Bacteria ◽  
In Vivo Model ◽  
Functional Changes ◽  
E Coli ◽  
C Elegans ◽  
Human Microbiota

Giardia duodenalis is the most common cause of parasitic diarrhea worldwide and a well-established risk factor for postinfectious irritable bowel syndrome. We hypothesized that Giardia-induced disruptions in host-microbiota interactions may play a role in the pathogenesis of giardiasis and in postgiardiasis disease. Functional changes induced by Giardia in commensal bacteria and the resulting effects on Caenorhabditis elegans were determined. Although Giardia or bacteria alone did not affect worm viability, combining commensal Escherichia coli bacteria with Giardia became lethal to C. elegans. Giardia also induced killing of C. elegans with attenuated Citrobacter rodentium espF and map mutant strains, human microbiota from a healthy donor, and microbiota from inflamed colonic sites of ulcerative colitis patient. In contrast, combinations of Giardia with microbiota from noninflamed sites of the same patient allowed for worm survival. The synergistic lethal effects of Giardia and E. coli required the presence of live bacteria and were associated with the facilitation of bacterial colonization in the C. elegans intestine. Exposure to C. elegans and/or Giardia altered the expression of 172 genes in E. coli. The genes affected by Giardia included hydrogen sulfide biosynthesis (HSB) genes, and deletion of a positive regulator of HSB genes, cysB, was sufficient to kill C. elegans even in the absence of Giardia. Our findings indicate that Giardia induces functional changes in commensal bacteria, possibly making them opportunistic pathogens, and alters host-microbe homeostatic interactions. This report describes the use of a novel in vivo model to assess the toxicity of human microbiota.

scholarly journals A host-directed macrocyclic peptide therapeutic for MDR gram negative bacterial infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justin B. Schaal ◽  
Yoshihiro Eriguchi ◽  
Dat Q. Tran ◽  
Patti A. Tran ◽  
Chase Hawes ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Cyclic Peptide ◽  
Mouse Serum ◽  
E Coli ◽  
Global Consensus ◽  
Carbapenem Resistant ◽  
Dose Levels ◽  
Further Development ◽  
Macrocyclic Peptide

AbstractThe emergence of infections by carbapenem resistant Enterobacteriaceae (CRE) pathogens has created an urgent public health threat, as carbapenems are among the drugs of last resort for infections caused by a growing fraction of multi-drug resistant (MDR) bacteria. There is global consensus that new preventive and therapeutic strategies are urgently needed to combat the growing problem of MDR bacterial infections. Here, we report on the efficacy of a novel macrocyclic peptide, minimized theta-defensin (MTD)-12813 in CRE sepsis. MTD12813 is a theta-defensin inspired cyclic peptide that is highly effective against CRE pathogens K. pneumoniae and E. coli in vivo. In mouse septicemia models, single dose administration of MTD12813 significantly enhanced survival by promoting rapid host-mediated bacterial clearance and by modulating pathologic cytokine responses, restoring immune homeostasis, and preventing lethal septic shock. The peptide lacks direct antibacterial activity in the presence of mouse serum or in peritoneal fluid, further evidence for its indirect antibacterial mode of action. MTD12813 is highly stable in biological matrices, resistant to bacterial proteases, and nontoxic to mice at dose levels 100 times the therapeutic dose level, properties which support further development of the peptide as a first in class anti-infective therapeutic.

scholarly journals In vivo targeting of E. coli with vancomycin-arginine

2021 ◽  
Author(s):  
Lewis F. Neville ◽  
Itamar Shalit ◽  
Peter A. Warn ◽  
Marc H. Scheetz ◽  
Jiuzhi Sun ◽  
...  
Keyword(s):  
Low Frequency ◽  
Muscle Model ◽  
Thigh Muscle ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Further Development

The ability of vancomycin-arginine (V-r) to extend the spectrum of activity of glycopeptides to gram-negative bacteria was investigated. Its MIC towards E. coli including β-lactamase expressing Ambler classes A, B, and D was 8-16μg/ml. Addition of 8×MIC V-r to E. coli was acutely bactericidal and associated with a low frequency of resistance (< 2.3×10−10). In vivo, V-r markedly reduced E. coli burden by >7 log10 CFU/g in a thigh muscle model. These data warrant further development of V-r in combatting E. coli, including resistant forms.

scholarly journals Citrobacter rodentium lifA/efa1 Is Essential for Colonic Colonization and Crypt Cell Hyperplasia In Vivo

2005 ◽  
Vol 73 (3) ◽  
pp. 1441-1451 ◽  
Author(s):  
Jan-Michael A. Klapproth ◽  
Maiko Sasaki ◽  
Melanie Sherman ◽  
Brian Babbin ◽  
Michael S. Donnenberg ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bacterial Colonization ◽  
Crypt Cell ◽  
Enteric Infection ◽  
Citrobacter Rodentium ◽  
Wild Type ◽  
E Coli ◽  
Epithelial Regeneration ◽  
Crypt Cell Proliferation

ABSTRACT Previously, we have identified a large gene (lifA, for lymphocyte inhibitory factor A) in enteropathogenic Escherichia coli (EPEC) encoding a protein termed lymphostatin that suppresses cytokine expression in vitro. This protein also functions as an adhesion factor for enterohemorrhagic E. coli (EHEC) and Shiga toxin-producing E. coli and is alternatively known as efa1 (EHEC factor for adherence 1). The lifA/efa1 gene is also present in Citrobacter rodentium, an enteric pathogen that causes a disease termed transmissible murine colonic hyperplasia (TMCH), which induces colitis and massive crypt cell proliferation, in mice. To determine if lifA/efa1 is required for C. rodentium-induced colonic pathology in vivo, three in-frame mutations were generated, disrupting the glycosyltransferase (GlM12) and protease (PrMC31) motifs and a domain in between that does not encode any known activity (EID3). In contrast to infection with wild-type C. rodentium, that with any of the lifA/efa1 mutant strains did not induce weight loss or TMCH. Enteric infection with motif mutants GlM12 and PrM31 resulted in significantly reduced colonization counts during the entire 20-day course of infection. In contrast, EID3 was indistinguishable from the wild type during the initial colonic colonization, but cleared rapidly after day 8 of the infection. The colonic epithelium of all infected mice displayed increased epithelial regeneration. However, significantly increased regeneration was observed by day 20 only in mice infected with the wild-type in comparison to those infected with lifA/efa1 mutant EID3. In summary, lifA/efa1 is a critical gene outside the locus for enterocyte effacement that regulates bacterial colonization, crypt cell proliferation, and epithelial cell regeneration.

scholarly journals Effects of Orally Administered Epidermal Growth Factor on Enteropathogenic Escherichia coli Infection in Rabbits

1998 ◽  
Vol 66 (10) ◽  
pp. 4917-4923 ◽  
Author(s):  
Andre Buret ◽  
Merle E. Olson ◽  
D. Grant Gall ◽  
James A. Hardin
Keyword(s):  
Escherichia Coli ◽  
Weight Gain ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Brush Border ◽  
Bacterial Colonization ◽  
E Coli ◽  
Epidermal Growth

ABSTRACT The increased intestinal absorption induced by epidermal growth factor (EGF) is associated with diffuse lengthening of brush border microvilli. The aim of this study was to examine the in vivo effects of oral administration of EGF during infection with enteropathogenicEscherichia coli. New Zealand White rabbits (4 weeks old) received orogastric EGF daily starting 3 days prior to infection with enteropathogenic E. coli RDEC-1 and were compared with sham-treated infected animals and uninfected controls. Weight gain, food intake, fecal E. coli, and stool consistency were assessed daily. On day 10, segments of jejunum, ileum, proximal, and distal colon were assessed for gram-negative bacterial colonization, disaccharidase activities, and epithelial ultrastructure. Effects of EGF on E. coli RDEC-1 proliferation were studied in vitro.E. coli RDEC-1 caused diarrhea and reduced weight gain. Seven days postinfection, the small and large intestines were colonized with numerous bacteria, brush border microvilli were disrupted, and maltase and sucrase activities were significantly reduced in the jejunum. Daily treatment with EGF prevented the occurrence of diarrhea and reduction of weight gain. These effects were associated with significant inhibition of E. coli colonization in the small and large intestine, improved jejunal maltase and sucrase activities and reduced microvillous injury. EGF did not affect the proliferation of E. coli in vitro. The findings suggest that EGF protects the gastrointestinal tract against colonization by enteropathogenicE. coli.

scholarly journals Follow Me! A Tale of Avian Heart Development with Comparisons to Mammal Heart Development

2020 ◽  
Vol 7 (1) ◽  
pp. 8 ◽  
Author(s):  
Rusty Lansford ◽  
Sandra Rugonyi
Keyword(s):  
Heart Development ◽  
Avian Embryos ◽  
Non Invasive ◽  
Heart Formation ◽  
Ease Of Access ◽  
Invasive Techniques ◽  
Further Development ◽  
Chicken Development ◽  
Study Development

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can then be covered, and the embryo returned to the incubator for the desired amount of time, and observed during further development. Up to about 4 days of chicken development (out of 21 days of incubation), when the egg is opened the embryo is on top of the yolk, and its heart is on top of its body. This allows easy imaging of heart formation and heart development using non-invasive techniques, including regular optical microscopy. After day 4, the embryo starts sinking into the yolk, but still imaging technologies, such as ultrasound, can tomographically image the embryo and its heart in vivo. Importantly, because like the human heart the avian heart develops into a four-chambered heart with valves, heart malformations and pathologies that human babies suffer can be replicated in avian embryos, allowing a unique developmental window into human congenital heart disease. Here, we review avian heart formation and provide comparisons to the mammalian heart.

scholarly journals Improved pentamethine cyanine nanosensors for optoacoustic imaging of pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew D. Laramie ◽  
Benjamin L. Fouts ◽  
William M. MacCuaig ◽  
Emmanuel Buabeng ◽  
Meredith A. Jones ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Contrast Agents ◽  
Optical Imaging ◽  
Silica Nanoparticles ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Optoacoustic Imaging ◽  
Initial Development ◽  
Imaging Technology

AbstractOptoacoustic imaging is a new biomedical imaging technology with clear benefits over traditional optical imaging and ultrasound. While the imaging technology has improved since its initial development, the creation of dedicated contrast agents for optoacoustic imaging has been stagnant. Current exploration of contrast agents has been limited to standard commercial dyes that have already been established in optical imaging applications. While some of these compounds have demonstrated utility in optoacoustic imaging, they are far from optimal and there is a need for contrast agents with tailored optoacoustic properties. The synthesis, encapsulation within tumor targeting silica nanoparticles and applications in in vivo tumor imaging of optoacoustic contrast agents are reported.

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