Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance be...Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity.Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.In addition,bacterial derivatives,including outer membrane vesicles(OMVs)produced by bacterial secretion and nanovesicles synthesized by modification of OMVs,could enhance antitumor immunity while improving safety.This perspective discusses the unique advantages of engineered bacteria and their derivatives for immunotherapy,as well as the challenges that need to be overcome to achieve clinical translation.展开更多
Vibrio splendidus is an important opportunistic pathogen ubiquitously present in the marine environment,exhibiting virulence to a variety of cultured animals.The extracellular products secreted by V.splendidus are cru...Vibrio splendidus is an important opportunistic pathogen ubiquitously present in the marine environment,exhibiting virulence to a variety of cultured animals.The extracellular products secreted by V.splendidus are crucial to bacterial survival and virulence.In this study,the secretion of outer membrane vesicles(OMVs)by V.splendidus was determined,purified,and morphologically characterized.The protein composition of OMVs was analyzed by proteomic analysis.The results showed that approximately 120 proteins were contained in these OMVs,including outer membrane proteins,flagellins,ABC transporters,protease,and iron regulation proteins,etc.,which were involved in bacterial motility,formation of biofilms and the cell membrane components,and cellular localization based on their structural molecule activity,passive transmembrane transporter activity,channel activity,neurotransmitter receptor activity,extracellular ligand-gated ion channel activity,glutamate receptor activity,ligand-gated ion channel activity,and transmembrane signaling receptor activity.To explore the biological functions of OMVs in V.splendidus,the effects of OMVs on the bacterial adaption to iron limitation,antibiotic,and the coelomic fluid of the Apostichopus japonicus were confirmed.This study is the first time to show that V.splendidus secretes OMVs,and OMVs carry functional proteins that enhance bacterial survival under various stresses.展开更多
Alpha-hemolysin (HlyA) is an extracellular toxin secreted by Escherichia coli, targeting to plasma membranes of eukaryotic cells. Recently it was found that this toxin is released to external media associated to bacte...Alpha-hemolysin (HlyA) is an extracellular toxin secreted by Escherichia coli, targeting to plasma membranes of eukaryotic cells. Recently it was found that this toxin is released to external media associated to bacterial outer membrane vesicles (OMVs), but the hemolytic mechanism in this way has not been studied yet. Our results report that HlyA is the only protein present in OMVs that is responsible for erythrocyte lysis, and show that no fusion event is involved in the lytic mechanism of OMVs-HlyA. Furthermore, the specific hemolytic activity is approximately 10 fold higher than that of purified free-HlyA, showing the same relative lysis efficiency and specificity for erythrocytes from different species. OMVs could be an important auxiliary way of secretion, acting mainly as a concentration mechanism of HlyA near the target cells. Cell lysis would occur after toxin transfer from OMVs to target membranes, as demonstrated by hemolysis kinetic studies, lipid mixing and western blot assays.展开更多
The Manantali dam is located on the Bafing River in the Kayes region of Mali. It is the main tributary of the Senegal River. The water released from the dam provides year-round access to water for drinking, irrigation...The Manantali dam is located on the Bafing River in the Kayes region of Mali. It is the main tributary of the Senegal River. The water released from the dam provides year-round access to water for drinking, irrigation and livestock watering. The Manantali dam regulates the river’s flow, generates energy and supports agricultural development in all three countries (Mali, Mauritania, and Senegal). The aim of this article is to monitor changes in the physico-chemical quality of the water in the dam’s reservoir from 1989 (one year after the dam was impounded) to 2022. In order to carry out this work, we analysed the evolution of physico-chemical parameters in Stations 1 and 3 of the dam, on the basis of fluctuating water levels in the reservoir. The results obtained show a similarity in the parameters measured at the two stations, except for iron content, which is higher at Station 3. The average pH is weakly basic (7.44 at Station 1 and 7.29 at Station 3) and the average water temperature is between 26.5°C at Station 1 and 26.2°C at Station 3. The average conductivity of the water at Station 1 is 38.8 μS/cm and 39.8 μS/cm at Station 3, attesting to low mineralization of the water. The oxygen content of 5.75 mg/L at Station 1 and 5.00 mg/L at Station 3 shows good oxygenation of the water, which is favorable for the development of most fish and aquatic plant species. Ammonium levels of 0.02 mg/L at Station 1 and 0.06 mg/L at Station 3 show that the water is not contaminated. In addition, the Water Quality Index (WQI) was calculated, showing excellent water quality at Station 1 and good quality at Station 3. Overall, the results obtained show that the water is of good quality, enabling the authorities of the Organization for the Development of the Senegal River (OMVS) to achieve their development objectives.展开更多
Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic applic...Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.展开更多
基金supported by the National Natural Science Foundation of China(nos.82222035 and 82372106)the Shenzhen Medical Research Found(no.B2302041).
文摘Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity.Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.In addition,bacterial derivatives,including outer membrane vesicles(OMVs)produced by bacterial secretion and nanovesicles synthesized by modification of OMVs,could enhance antitumor immunity while improving safety.This perspective discusses the unique advantages of engineered bacteria and their derivatives for immunotherapy,as well as the challenges that need to be overcome to achieve clinical translation.
基金the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(No.LR20C190001)the National Natural Science Foundation of China(No.31972833)+1 种基金the Fundamental Research Funds for the Provincial Universities of Zhejiang(No.SJ LZ2020001)the K.C.Wong Magna Fund at Ningbo University。
文摘Vibrio splendidus is an important opportunistic pathogen ubiquitously present in the marine environment,exhibiting virulence to a variety of cultured animals.The extracellular products secreted by V.splendidus are crucial to bacterial survival and virulence.In this study,the secretion of outer membrane vesicles(OMVs)by V.splendidus was determined,purified,and morphologically characterized.The protein composition of OMVs was analyzed by proteomic analysis.The results showed that approximately 120 proteins were contained in these OMVs,including outer membrane proteins,flagellins,ABC transporters,protease,and iron regulation proteins,etc.,which were involved in bacterial motility,formation of biofilms and the cell membrane components,and cellular localization based on their structural molecule activity,passive transmembrane transporter activity,channel activity,neurotransmitter receptor activity,extracellular ligand-gated ion channel activity,glutamate receptor activity,ligand-gated ion channel activity,and transmembrane signaling receptor activity.To explore the biological functions of OMVs in V.splendidus,the effects of OMVs on the bacterial adaption to iron limitation,antibiotic,and the coelomic fluid of the Apostichopus japonicus were confirmed.This study is the first time to show that V.splendidus secretes OMVs,and OMVs carry functional proteins that enhance bacterial survival under various stresses.
文摘Alpha-hemolysin (HlyA) is an extracellular toxin secreted by Escherichia coli, targeting to plasma membranes of eukaryotic cells. Recently it was found that this toxin is released to external media associated to bacterial outer membrane vesicles (OMVs), but the hemolytic mechanism in this way has not been studied yet. Our results report that HlyA is the only protein present in OMVs that is responsible for erythrocyte lysis, and show that no fusion event is involved in the lytic mechanism of OMVs-HlyA. Furthermore, the specific hemolytic activity is approximately 10 fold higher than that of purified free-HlyA, showing the same relative lysis efficiency and specificity for erythrocytes from different species. OMVs could be an important auxiliary way of secretion, acting mainly as a concentration mechanism of HlyA near the target cells. Cell lysis would occur after toxin transfer from OMVs to target membranes, as demonstrated by hemolysis kinetic studies, lipid mixing and western blot assays.
文摘The Manantali dam is located on the Bafing River in the Kayes region of Mali. It is the main tributary of the Senegal River. The water released from the dam provides year-round access to water for drinking, irrigation and livestock watering. The Manantali dam regulates the river’s flow, generates energy and supports agricultural development in all three countries (Mali, Mauritania, and Senegal). The aim of this article is to monitor changes in the physico-chemical quality of the water in the dam’s reservoir from 1989 (one year after the dam was impounded) to 2022. In order to carry out this work, we analysed the evolution of physico-chemical parameters in Stations 1 and 3 of the dam, on the basis of fluctuating water levels in the reservoir. The results obtained show a similarity in the parameters measured at the two stations, except for iron content, which is higher at Station 3. The average pH is weakly basic (7.44 at Station 1 and 7.29 at Station 3) and the average water temperature is between 26.5°C at Station 1 and 26.2°C at Station 3. The average conductivity of the water at Station 1 is 38.8 μS/cm and 39.8 μS/cm at Station 3, attesting to low mineralization of the water. The oxygen content of 5.75 mg/L at Station 1 and 5.00 mg/L at Station 3 shows good oxygenation of the water, which is favorable for the development of most fish and aquatic plant species. Ammonium levels of 0.02 mg/L at Station 1 and 0.06 mg/L at Station 3 show that the water is not contaminated. In addition, the Water Quality Index (WQI) was calculated, showing excellent water quality at Station 1 and good quality at Station 3. Overall, the results obtained show that the water is of good quality, enabling the authorities of the Organization for the Development of the Senegal River (OMVS) to achieve their development objectives.
基金supported in part by the National Natural Science Foundation of China (81472820, 81773255, 81071860 and 81602702)Jiangsu Special Program for Clinical Medical Science and Technology (BL2014054)+2 种基金the Natural Science Foundation of Jiangsu Province of China (BK20160126)the Fundamental Research Funds for the Central Universities (021414380223 and 14380336/1-2)Six talent peaks project in Jiangsu Province to JW
文摘Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.
