To obtain therapeutically effective new antibiotics, we first searched for bacterial culture supernatants with antimicrobial activity in vitro and then performed a secondary screening using the silkworm infection model. Through further purification of the in vivo activity, we obtained a compound with a previously uncharacterized structure and named it 'lysocin E'. Lysocin E interacted with menaquinone in the bacterial membrane to achieve its potent bactericidal activity, a mode of action distinct from that of any other known antibiotic, indicating that lysocin E comprises a new class of antibiotic. This is to our knowledge the first report of a direct interaction between a small chemical compound and menaquinone that leads to bacterial killing. Furthermore, lysocin E decreased the mortality of infected mice. To our knowledge, lysocin E is the first compound identified and purified by quantitative measurement of therapeutic effects in an invertebrate infection model that exhibits robust in vivo effects in mammals.
The Bohai Sea is characterized as a semi-closed sea with limited water exchange ability, which has been regarded as one of the most contaminated regions in China and has attracted public attention over the past decades. In recent years, the rapid industrialization and urbanization around the coastal region has resulted in a severe pollution pressure in the Bohai Sea. Although efforts from official government and scientific experts have been made to protect and restore the marine ecosystem, satisfactory achievements were not gained. Moreover, partial coastal areas in the Bohai Sea seemingly remain heavily polluted. In this study, we focused on five coastal regions around the Bohai Sea to study the spatial distribution pattern of trace elements in the sediments and their ecological risk. A total of 108 sediment samples were analyzed to determine the contamination degree of trace elements (Cu, Cd, As, Pb, Zn, Cr, and Hg). Contamination factor (CF), pollution load index (PLI), geoaccumulation index (I), and potential ecological risk index (PERI) were utilized to assess the pollution extent of these metals. Spatial distribution patterns revealed that the sedimentary environments of coastal Bohai were in good condition, except Jinzhou Bay, according to the Marine Sediment Quality of China. The concentrations of Hg and Cd were considerably higher than the average upper crust value and presented high potential ecological risk and considerable potential ecological risk, respectively. The overall environment quality of the coastal Bohai Sea does not seem to pose an extremely serious threat in terms of metal pollution. Thus, the government should continue implementing pollution control programs in the Bohai Sea.
Lysocin E is a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus. For unclear reasons, the antibacterial activity of lysocin E in a mouse systemic infection model is higher than expected from in vitro results, and the in vitro activity is enhanced by addition of bovine serum. Here, we confirm that serum from various species, including humans, increases lysocin E antimicrobial activity, and identify apolipoprotein A-I (ApoA-I) as an enhancing factor. ApoA-I increases the antibacterial activity of lysocin E when added in vitro, and the antibiotic displays reduced activity in ApoA-I gene knockout mice. Binding of ApoA-I to lysocin E is enhanced by lipid II, a cell-wall synthesis precursor found in the bacterial membrane. Thus, the antimicrobial activity of lysocin E is potentiated through interactions with host serum proteins and microbial components.
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