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  • 1
    In: EMBO reports, EMBO, Vol. 22, No. 6 ( 2021-06-04)
    Type of Medium: Online Resource
    ISSN: 1469-221X , 1469-3178
    Language: English
    Publisher: EMBO
    Publication Date: 2021
    detail.hit.zdb_id: 2025376-X
    SSG: 12
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  • 2
    In: eLife, eLife Sciences Publications, Ltd, Vol. 10 ( 2021-07-05)
    Abstract: Urinary tract infections are one of the most common reasons people need antibiotics. These bacterial infections are typically caused by uropathogenic Escherichia coli (also known as UPEC), which either float freely in the urine and wash away when the bladder empties, or form communities inside cells that the bladder struggles to clear. It is possible that the bacteria living within cells are also more protected from the immune system and antibiotics. But this is hard to study in animal models. To overcome this, Sharma et al. built a ‘bladder-chip’ which mimics the interface between the blood vessels and the tissue layers of the human bladder. Similar chip devices have also been made for other organs. However, until now, no such model had been developed for the bladder. On the chip created by Sharma et al. is a layer of bladder cells which sit at the bottom of a channel filled with diluted human urine. These cells were infected with UPEC, and then imaged over time to see how the bacteria moved, interacted with the bladder cells, and aggregated together. Immune cells from human blood were then added to a vascular channel underneath the bladder tissue, which is coated with endothelial cells that normally line blood vessels. The immune cells rapidly crossed the endothelial barrier and entered the bladder tissue, and swarmed around sites of infection. In some instances, they released the contents of their cells to form net-like traps to catch the bacteria. But these traps failed to remove the bacteria living inside bladder cells. Antibiotics were then added to the urine flowing over the bladder cells as well as the vascular channel, similar to how drugs would be delivered in live human tissue. Sharma et al. discovered that the antibiotics killed bacteria residing in bladder cells slower than bacteria floating freely in the urine. Furthermore, they found that bacteria living in tightly packed communities within bladder cells were more likely to survive treatment and go on to re-infect other parts of the tissue. Antibiotic resistance is a pressing global challenge, and recurrent urinary tract infections are a significant contributor. The bladder-chip presented here could further our understanding of how these bacterial infections develop in vivo and how good antibiotics are at removing them. This could help researchers identify the best dosing and treatment strategies, as well as provide a platform for rapidly testing new antibiotic drugs and other therapies.
    Type of Medium: Online Resource
    ISSN: 2050-084X
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2021
    detail.hit.zdb_id: 2687154-3
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  • 3
    In: eLife, eLife Sciences Publications, Ltd, Vol. 9 ( 2020-11-24)
    Abstract: Tuberculosis is a contagious respiratory disease caused by the bacterium Mycobacterium tuberculosis . Droplets in the air carry these bacteria deep into the lungs, where they cling onto and infect lung cells. Only small droplets, holding one or two bacteria, can reach the right cells, which means that just a couple of bacterial cells can trigger an infection. But people respond differently to the bacteria: some develop active and fatal forms of tuberculosis, while many show no signs of infection. With no effective tuberculosis vaccine for adults, understanding why individuals respond differently to Mycobacterium tuberculosis may help develop treatments. Different responses to Mycobacterium tuberculosis may stem from the earliest stages of infection, but these stages are difficult to study. For one thing, tracking the movements of the few bacterial cells that initiate infection is tricky. For another, studying the molecules, called ‘surfactants’, that the lungs produce to protect themselves from tuberculosis can prove difficult because these molecules are necessary for the lungs to inflate and deflate normally. Normally, the role of a molecule can be studied by genetically modifying an animal so it does not produce the molecule in question, which provides information as to its potential roles. Unfortunately, due to the role of surfactants in normal breathing, animals lacking them die. Therefore, to reveal the role of some of surfactants in tuberculosis, Thacker et al. used ‘lung-on-chip’ technology. The ‘chip’ (a transparent device made of a polymer compatible with biological tissues) is coated with layers of cells and has channels to simulate air and blood flow. To see what effects surfactants have on M. tuberculosis bacteria, Thacker et al. altered the levels of surfactants produced by the cells on the lung-on-chip device. Two types of mouse cells were grown on the chip: lung cells and immune cells. When cells lacked surfactants, bacteria grew rapidly on both lung and immune cells, but when surfactants were present bacteria grew much slower on both cell types, or did not grow at all. Further probing showed that the surfactants pulled out proteins and fats on the surface of M. tuberculosis that help the bacteria to infect their host, highlighting the protective role of surfactants in tuberculosis. These findings lay the foundations for a system to study respiratory infections without using animals. This will allow scientists to study the early stages of Mycobacterium tuberculosis infection, which is crucial for finding ways to manage tuberculosis.
    Type of Medium: Online Resource
    ISSN: 2050-084X
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2020
    detail.hit.zdb_id: 2687154-3
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