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1.
Microb Cell Fact ; 23(1): 163, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824527

ABSTRACT

BACKGROUND: Type I interferons (IFN-I)-a group of cytokines with immunomodulatory, antiproliferative, and antiviral properties-are widely used as therapeutics for various cancers and viral diseases. Since IFNs are proteins, they are highly susceptible to degradation by proteases and by hydrolysis in the strong acid environment of the stomach, and they are therefore administered parenterally. In this study, we examined whether the intestinal bacterium, enteropathogenic Escherichia coli (EPEC), can be exploited for oral delivery of IFN-Is. EPEC survives the harsh conditions of the stomach and, upon reaching the small intestine, expresses a type III secretion system (T3SS) that is used to translocate effector proteins across the bacterial envelope into the eukaryotic host cells. RESULTS: In this study, we developed an attenuated EPEC strain that cannot colonize the host but can secrete functional human IFNα2 variant through the T3SS. We found that this bacteria-secreted IFN exhibited antiproliferative and antiviral activities similar to commercially available IFN. CONCLUSION: These findings present a potential novel approach for the oral delivery of IFN via secreting bacteria.


Subject(s)
Enteropathogenic Escherichia coli , Type III Secretion Systems , Enteropathogenic Escherichia coli/metabolism , Humans , Type III Secretion Systems/metabolism , Interferon-alpha/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/metabolism , Interferon alpha-2/metabolism , Cell Proliferation/drug effects
2.
PLoS One ; 9(2): e88468, 2014.
Article in English | MEDLINE | ID: mdl-24516662

ABSTRACT

Recent studies of the larvae of coral-reef fishes reveal that these tiny vertebrates possess remarkable swimming capabilities, as well as the ability to orient to olfactory, auditory, and visual cues. While navigation according to reef-generated chemicals and sounds can significantly affect dispersal, the effect is limited to the vicinity of the reef. Effective long-distance navigation requires at least one other capacity-the ability to maintain a bearing using, for example, a sun compass. Directional information in the sun's position can take the form of polarized-light related cues (i.e., e-vector orientation and percent polarization) and/or non-polarized-light related cues (i.e., the direct image of the sun, and the brightness and spectral gradients). We examined the response to both types of cues using commercially-reared post-larvae of the spine-cheeked anemonefish Premnas biaculeatus. Initial optomotor trials indicated that the post-larval stages are sensitive to linearly polarized light. Swimming directionality was then tested using a Drifting In-Situ Chamber (DISC), which allowed us to examine the response of the post-larvae to natural variation in light conditions and to manipulated levels of light polarization. Under natural light conditions, 28 of 29 post-larvae showed significant directional swimming (Rayleigh's test p<0.05, R = 0.74±0.23), but to no particular direction. Swimming directionality was positively affected by sky clarity (absence of clouds and haze), which explained 38% of the observed variation. Moreover, post-larvae swimming under fully polarized light exhibited a distinct behavior of tracking the polarization axis, as it rotated along with the DISC. This behavior was not observed under partially-polarized illumination. We view these findings as an indication for the use of sun-related cues, and polarized light signal in specific, by orienting coral-reef fish larvae.


Subject(s)
Behavior, Animal/physiology , Coral Reefs , Fishes/physiology , Orientation/physiology , Animals , Cues , Light , Swimming/physiology
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