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40 results on '"Langford, Paul R."'

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Author

Aizawa, Shin-Ichi, primary, Alberdi, Pilar, additional, Alexander, David C., additional, Alía, Alberto, additional, Allison, D.G., additional, Amyes, Sebastian G.B., additional, An, Haoran, additional, Andrade, María J., additional, Antelmann, Haike, additional, Arias, Cesar A., additional, Asensio, Miguel A., additional, Axell-House, Dierdre B., additional, Bae, Hee-Won, additional, Baena, Laura Muñoz, additional, Baig, Abdul Mannan, additional, Bailey, Spenser O., additional, Baize, Sylvain, additional, Baldi, Pablo C., additional, Barbosa, Angela Silva, additional, Barbuddhe, Sukhadeo B., additional, Bard, Emilie, additional, Barry, Eileen M., additional, Basarab, Gregory S., additional, Beloborodova, N.V, additional, Bermúdez, Elena, additional, Bidmos, Fadil A., additional, Bisgaard, Magne, additional, Blakely, Garry W., additional, Bloch, Evan, additional, Boesen, Thias Oberg, additional, Bose, Dipayan, additional, Botero, Javier Enrique, additional, Bouabe, Hicham, additional, Bouchard, Michael J., additional, Bozue, Joel A., additional, Bradbury, Richard S., additional, Brett Moreau, G., additional, Cabezas-Cruz, Alejandro, additional, Cai, Rong-Jun, additional, Calderón, Enrique J., additional, Cao, Boyang, additional, Carmena, David, additional, Carvalho, Eneas, additional, Caulfield, Amanda D., additional, Cen, Shan, additional, Chai, Jong-Yil, additional, Chamberland, Robin R., additional, Champredon, David, additional, Chan, Edward D., additional, Charbon, Godefroid, additional, Chato, Connor, additional, Chelomina, G.N., additional, Chen, Jingyu, additional, Chen, Min, additional, Chen, Shuyu, additional, Chen, Suilin, additional, Chen, Yanfei, additional, Chen, Zhaoyuan, additional, Cheng, Aimin, additional, Cheng, Keding, additional, Chiu, Charles Y., additional, Cho, You-Hee, additional, Christensen, Henrik, additional, Chrtdernevskaya, E.A., additional, Contreras, Adolfo, additional, Contreras, Marinela, additional, Córdoba, Juan J., additional, Córdoba, María G., additional, Costa, Rita, additional, Cote, Christopher K., additional, Cui, Xiangling, additional, Cui, Yujun, additional, Dacal, Elena, additional, Dammann, Allison N., additional, Das, Shubhagata, additional, Dashti, Alejandro, additional, de la Fuente, José, additional, de la Garza, Mireya, additional, Delgado, Josué, additional, Delgado-Cuesta, Juan, additional, Deng, Haiteng, additional, Deng, Li, additional, Dey, Debajit, additional, Dhama, Kuldeep, additional, Diego, Juan García-Bernalt, additional, Ding, Hao, additional, Doern, Christopher D., additional, Dorman, Charles J., additional, Du, Zongmin, additional, Dunbar, Sherry A., additional, Duthie, Malcolm, additional, Dybvig, Kevin F., additional, Eakin, Ann E., additional, Eallonardo, Samuel J., additional, Eberly, Allison R., additional, Echeverry, Adriana Jaramillo, additional, Egland, Paul G., additional, El Zowalaty, Mohamed E., additional, Endsley, Janice Jones, additional, Eom, Keeseon S., additional, Evans, Benjamin A., additional, Falkinham, Joseph O., additional, Feng, Siwei, additional, Feng, Yaoyu, additional, Feng, Zongdi, additional, Fernández-Soto, Pedro, additional, Ferreira, Roux-Cil, additional, Flores-Huerta, Nadia, additional, Foster, Timothy J., additional, Fox-Moon, Sandra M., additional, Fraga, Tatiana Rodrigues, additional, Fredricks, David N., additional, Freitag, Nancy E., additional, Frimodt-Møller, Jakob, additional, Fuller, Risa, additional, Ganesh, Balasubramanian, additional, Gao, Ning, additional, García-Carnero, Laura C., additional, Garzetti, Debora, additional, Geoghegan, Joan A., additional, Ghenim, Raed, additional, Giambartolomei, Guillermo H., additional, Gilbert, Nicole M., additional, Gillis, Thomas Phillip, additional, Gladstone, Camilla A., additional, Gómez-Gaviria, Manuela, additional, Gómez-Marín, Jorge E., additional, Gong, Tengfang, additional, González, Ramón A., additional, Gray-Owen, Scott D., additional, Gu, Bing, additional, Guzmán-Téllez, Paula, additional, Hajal, Caroline, additional, Han, Yanping, additional, Hao, Yi, additional, Harrington, Amanda T., additional, Harris, Jason B., additional, Harvill, Eric T., additional, Hasan, S. Saif, additional, He, Guang-Jun, additional, He, Yongqun, additional, Heffron, Jared D., additional, Hidalgo, Paloma, additional, Hindiyeh, Musa Y., additional, Hreha, Teri N., additional, Hu, Xiaoyu, additional, Huang, Guanghua, additional, Huang, Jiangqing, additional, Huang, Liang, additional, Huang, Shifeng, additional, Huang, Xingxu, additional, Huang, Xueting, additional, Huang, Yilun, additional, Huffman, Anthony, additional, Humphreys, Tricia L., additional, Hunstad, David A., additional, Inglis, Timothy J.J., additional, Isaac, Lourdes, additional, Jacobs, Samantha E., additional, Janowicz, Diane M., additional, Jeon, Hyeong-Kyu, additional, Ji, Quanjiang, additional, Jia, Qi, additional, Jia, Wei, additional, Jin, Shouguang, additional, Jneidi, Lama, additional, Jose, Shinsmon, additional, Jung, Bong-Kwang, additional, Kattan, Randa, additional, Kaushik, Rahul, additional, Khare, Reeti, additional, Kim, Eun Sook, additional, Kirn, Thomas J., additional, Koo, Hyun, additional, Köster, Pamela C., additional, Krause, Peter J., additional, Kumar, Sanjai, additional, Kupz, Andreas, additional, Lambert, P.A., additional, Lamont, Richard J., additional, Langford, Paul R., additional, Lebeaux, David, additional, Legname, Giuseppe, additional, Li, Bin, additional, Li, Chunhao, additional, Li, Fen, additional, Li, Jun, additional, Li, Lanjuan, additional, Li, Ruofan, additional, Li, Ruoyu, additional, Li, Ting, additional, Li, Yang-Yang, additional, Li, Yanhua, additional, Li, Zhuorong, additional, Liang, Xiaomeng, additional, Liao, Guojian, additional, Lin, Ping, additional, Ling, Yun, additional, Liu, Bo, additional, Liu, Dongyou, additional, Liu, Guohua, additional, Liu, Huidi, additional, Liu, Jiafeng, additional, Liu, Jintao, additional, Liu, Qi, additional, Liu, Shu-Lin, additional, Liu, Taiping, additional, Liu, Tongbao, additional, Liu, Wei, additional, Liu, Yan, additional, Liu, Yanni, additional, Liu, Yisong, additional, Liu, Yuan, additional, Løbner-Olesen, Anders, additional, Loeffelholz, Michael, additional, Lu, Hongzhou, additional, Luna, Brian, additional, Ma, Bingting, additional, Ma, Chengying, additional, Ma, Shuang, additional, Ma, TianLi, additional, Madan, Rajat, additional, Mahle, Rachael E., additional, Mahlen, Steven D., additional, Malik, Satya Veer Singh, additional, Malik, Yashpal Singh, additional, Malvy, Denis, additional, Mann, Barbara J., additional, Marasini, Daya, additional, Maris, Alexander S., additional, Marjomäki, Varpu, additional, Marjuki, Henju, additional, Martín, Alberto, additional, Martín, Irene, additional, Martínez-Castillo, Moisés, additional, Martínez-Pabón, María Cecilia, additional, Mathison, Blaine A., additional, Ma’ayeh, Showgy, additional, McDowell, Andrew, additional, McLaughlin, Stephanie E., additional, McSheffrey, Gordon G., additional, Medrano, Francisco J., additional, Meehan, Conor J., additional, Mehta, Dhwani, additional, Mejía-Oquendo, Manuela, additional, Melo-Cristino, José, additional, Mendoza-Barberá, Elena, additional, Meng, Xinan, additional, Merino, Susana, additional, Merritt, Adam J., additional, Miller, Steve, additional, Miller, William R., additional, Minamino, Tohru, additional, Mirzaei, Mohammadali Khan, additional, Mora-Montes, Héctor M., additional, Mortensen, Joel, additional, Mostafa, Heba H., additional, Muhsen, Khitam, additional, Mujahed, Ahlam, additional, Muro, Antonio, additional, Murphy, Olwen C., additional, Newton, Hayley J., additional, Nguyen, April H., additional, Nichols, Wright W., additional, Niu, Siqiang, additional, Núñez, Félix, additional, Obregon, Dasiel, additional, Okamoto, Akira, additional, Okutani, Akiko, additional, Olabode, Abayomi, additional, Omar, Muna, additional, Ong, Edison, additional, Ouyang, Zhiming, additional, Pacak, Christina A., additional, Pacheco-Yépez, Judith, additional, Palmer, John, additional, Pang, Xiaoli, additional, Paredes-Sabja, Daniel, additional, Peng, Zhong, additional, Peng, Zonggen, additional, Pérez-Nevado, Francisco, additional, Poon, Art, additional, Pospíšilová, Petra, additional, Potts, Caelin C., additional, Pu, Qinqin, additional, Pujic, Petar, additional, Qi, Rui, additional, Qian, Chenyun, additional, Qian, Liu, additional, Qin, Aiping, additional, Qu, Fen, additional, Rakin, Alexander, additional, Ramesh, Ashwin, additional, Ramirez, Mario, additional, Rao, Yu, additional, Ratner, Adam J., additional, Rawool, Deepak B., additional, Rehman, Asma, additional, Ren, Jie, additional, Ren, Ping, additional, Retchless, Adam C., additional, Robertson, Erle S., additional, Rodríguez, Alicia, additional, Rodriguez, Azucena, additional, Rodríguez-Medina, Carolina, additional, Rodriguez-Nava, Veronica, additional, Rohde, Manfred, additional, Romero-Rodríguez, Alba, additional, Rosales-Morgan, Gabriela, additional, Rosenkranz, Andrea L., additional, Ruiz-Moyano, Santiago, additional, Ruokolainen, Visa, additional, Sabateen, Ali, additional, Sahu, Radhakrishna, additional, Sails, Andrew, additional, Sang, Yu, additional, Santana, Clarissa H., additional, Santos, Jesus A., additional, Santos, Renato L., additional, Schmitz, Jonathan E., additional, Serrano-Luna, Jesús, additional, Shen, Jianzhong, additional, Shen, Zhangqi, additional, Shibayama, Mineko, additional, Shirtliff, Mark E., additional, Silva-Costa, Catarina, additional, Silva-Olivares, Angélica, additional, Singh, Niraj Kumar, additional, Šmajs, David, additional, Smith, Robert P., additional, Smith, Sophie, additional, Snyder, Lori A.S., additional, Song, Yinggai, additional, Soro, Aurea Simon, additional, Spearman, Paul, additional, Spellberg, Brad, additional, Sprague, Lisa D., additional, Stratton, Charles W., additional, Strenk, Susan M., additional, Strugnell, Richard A., additional, Sun, Keer, additional, Suo, Xun, additional, Suzuki-Hatano, Silveli, additional, Svärd, Staffan, additional, Talbot, Elizabeth A., additional, Tamez-Castrellón, Alma K., additional, Tan, Nie, additional, Tang, Cynthia Y., additional, Tang, Yi-Wei, additional, Tao, Jia, additional, Tao, Lili, additional, Terrero-Salcedo, David, additional, Tharmalingam, Jayaraman, additional, Thwe, Phyu M., additional, Tiamani, Kawtar, additional, Tomás, Juan M., additional, Topaz, Nadav, additional, Tsai, Ang-Chen, additional, Tsalik, Ephraim L., additional, Tuomanen, Elaine I., additional, Turenne, Christine Y., additional, Tyagi, Anuj, additional, Uprety, Priyanka, additional, Valour, Florent, additional, van Hensbergen, Vincent P., additional, Venkatesan, Arun, additional, Vergis, Jess, additional, Villar, Margarita, additional, Vollmer, Waldemar, additional, Waites, Ken B., additional, Wan, Xiu-Feng, additional, Wang, Guiqing, additional, Wang, Lijun, additional, Wang, Lin, additional, Wang, Linqi, additional, Wang, Xiangru, additional, Wang, Xin, additional, Wang, Xinjie, additional, Wang, Ya-Ting, additional, Wang, Yang, additional, Wang, Yating, additional, Weil, Ana A., additional, Welkos, Susan L., additional, Wengenack, Nancy L., additional, Westblade, Lars F., additional, Whitfield, Chris, additional, Wu, Hui, additional, Wu, Lijuan, additional, Wu, Min, additional, Wu, Yarong, additional, Wu, Zhaowei, additional, Xiang, Ye, additional, Xiao, Di, additional, Xiao, Li, additional, Xiao, Lihua, additional, Xu, Tao, additional, Xu, Wenyue, additional, Xu, Xinping, additional, Xue, Jinling, additional, Yadav, Jay Prakash, additional, Yan, Junxiang, additional, Yan, Yixin, additional, Yang, Changmei, additional, Yang, Ruifu, additional, Yang, Ying, additional, Yao, Kaihu, additional, Yao, Yu-Feng, additional, Yeakle, Kyle C., additional, Yu, Demin, additional, Yu, Hao, additional, Yu, Xue-Jie, additional, Yuan, Zhenghong, additional, Zai, Wenjing, additional, Zhang, Jianzhong, additional, Zhang, Jing-Ren, additional, Zhang, Lanyue, additional, Zhang, Lijie, additional, Zhang, Qiwei, additional, Zhang, Wenbao, additional, Zhang, Wenhong, additional, Zhang, Xinxin, additional, Zhao, Youbao, additional, Zhou, Chuanmin, additional, Zhu, Feng, additional, Zhu, Jingting, additional, and Zhu, Yongqun, additional

Published
2024
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15. Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that control distinct phasevarions

Author

Nahar, Nusrat, primary, Tram, Greg, additional, Jen, Freda E-C, additional, Phillips, Zachary N, additional, Weinert, Lucy A, additional, Bossé, Janine T, additional, Jabbari, Jafar S, additional, Gouil, Quentin, additional, Du, Mei R M, additional, Ritchie, Matthew E, additional, Bowden, Rory, additional, Langford, Paul R, additional, Tucker, Alexander W, additional, Jennings, Michael P, additional, Turni, Conny, additional, Blackall, Patrick J, additional, and Atack, John M, additional

Published
2023
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17. Bolaamphiphile Analogues of 12-bis-THA Cl 2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens

Author

Di Blasio, Simona, primary, Clarke, Maria, additional, Hind, Charlotte K., additional, Asai, Masanori, additional, Laurence, Louis, additional, Benvenuti, Angelica, additional, Hassan, Mahnoor, additional, Semenya, Dorothy, additional, Man, DeDe Kwun-Wai, additional, Horrocks, Victoria, additional, Manzo, Giorgia, additional, Van Der Lith, Sarah, additional, Lam, Carolyn, additional, Gentile, Eugenio, additional, Annette, Callum, additional, Bosse, Janine, additional, Li, Yanwen, additional, Panaretou, Barry, additional, Langford, Paul R., additional, Robertson, Brian D., additional, Lam, Jenny K. W., additional, Sutton, J. Mark, additional, McArthur, Michael, additional, and Mason, A. James, additional

Published
2022
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18. Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that comprise distinct phasevarions

Author

Nahar, Nusrat, primary, Tram, Greg, additional, Jen, Freda E-C, additional, Phillips, Zachary N., additional, Weinert, Lucy A., additional, Bossé, Janine T., additional, Jabbari, Jafar S., additional, Gouil, Quentin, additional, Du, Mei R. M., additional, Ritchie, Matthew E., additional, Bowden, Rory, additional, Langford, Paul R., additional, Tucker, Alexander W., additional, Jennings, Michael P., additional, Turni, Conny, additional, Blackall, Patrick J., additional, and Atack, John M., additional

Published
2022
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19. The Metabolic Adaptation in Response to Nitrate Is Critical for Actinobacillus pleuropneumoniae Growth and Pathogenicity under the Regulation of NarQ/P

Author

Zhang, Qiuhong, primary, Tang, Hao, additional, Yan, Chaoyue, additional, Han, Weiyao, additional, Peng, Lu, additional, Xu, Jiajia, additional, Chen, Xiabing, additional, Langford, Paul R., additional, Bei, Weicheng, additional, Huang, Qi, additional, Zhou, Rui, additional, and Li, Lu, additional

Published
2022
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24. Bolaamphiphile Analogues of 12-bis-THA Cl2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens.

Author

Di Blasio, Simona, Clarke, Maria, Hind, Charlotte K., Asai, Masanori, Laurence, Louis, Benvenuti, Angelica, Hassan, Mahnoor, Semeny, Dorothy, DeDeKwun-WaiMan, Horrocks, Victoria, Manzo, Giorgia, Van Der Lith, Sarah, Lam, Carolyn, Gentile, Eugenio, Annette, Callum, Bosse, Janine, Yanwen Li, Panaretou, Barry, Langford, Paul R., and Robertson, Brian D.

Published
2023
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26. Rapid Detection of Actinobacillus pleuropneumoniae From Clinical Samples Using Recombinase Polymerase Amplification

Author

Stringer, Oliver W., primary, Li, Yanwen, additional, Bossé, Janine T., additional, Forrest, Matthew S., additional, Hernandez-Garcia, Juan, additional, Tucker, Alexander W., additional, Nunes, Tiago, additional, Costa, Francisco, additional, Mortensen, Preben, additional, Velazquez, Eduardo, additional, Penny, Paul, additional, Rodriguez-Manzano, Jesus, additional, Georgiou, Pantelis, additional, and Langford, Paul R., additional

Published
2022
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29. Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

Author

Bossé, Janine T, Li, Yanwen, Leanse, Leon G, Zhou, Liqing, Chaudhuri, Roy R, Peters, Sarah E, Wang, Jinhong, Maglennon, Gareth A, Holden, Matthew TG, Maskell, Duncan J, Tucker, Alexander W, Wren, Brendan W, Rycroft, Andrew N, Langford, Paul R, and BRaDP1T consortium

Abstract

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

Published
2021

30. Comparative Genome Sequence Analysis of Actinobacillus pleuropneumoniae Serovar 8 Isolates From Norway, Denmark, and the United Kingdom Indicates Distinct Phylogenetic Lineages and Differences in Distribution of Antimicrobial Resistance Genes

Author

Cohen, Liza Miriam, primary, Bossé, Janine T., additional, Stegger, Marc, additional, Li, Yanwen, additional, Langford, Paul R., additional, Kielland, Camilla, additional, Klem, Thea Blystad, additional, Gulliksen, Stine Margrethe, additional, Ranheim, Birgit, additional, Grøntvedt, Carl Andreas, additional, and Angen, Øystein, additional

Published
2021
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31. Rapid Detection and Typing of Actinobacillus pleuropneumoniae Serovars Directly From Clinical Samples: Combining FTA® Card Technology With Multiplex PCR

Author

Stringer, Oliver W., primary, Bossé, Janine T., additional, Lacouture, Sonia, additional, Gottschalk, Marcelo, additional, Fodor, László, additional, Angen, Øystein, additional, Velazquez, Eduardo, additional, Penny, Paul, additional, Lei, Liancheng, additional, Langford, Paul R., additional, and Li, Yanwen, additional

Published
2021
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33. Galleria mellonellaas an infection model for the virulent Mycobacterium tuberculosisH37Rv

Author

Asai, Masanori, Li, Yanwen, Spiropoulos, John, Cooley, William, Everest, David J., Kendall, Sharon L., Martín, Carlos, Robertson, Brian D., Langford, Paul R., and Newton, Sandra M.

Abstract

ABSTRACTTuberculosis (TB), caused by Mycobacterium tuberculosis(MTB), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for more ethically acceptable, economical, and reproducible TB infection models capable of mimicking key aspects of disease. Here, we demonstrate and present a basic description of how Galleria mellonella(the greater wax moth, Gm) larvae can be used as a low cost, rapid, and ethically more acceptable model for TB research. This is the first study to infect Gmwith the fully virulent MTBH37Rv, the most widely used strain in research. Infection of Gmwith MTBresulted in a symptomatic lethal infection, the virulence of which differed from both attenuated Mycobacterium bovisBCG and auxotrophic MTBstrains. The Gm-MTBmodel can also be used for anti-TB drug screening, although CFU enumeration from Gmis necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of MTBisogenic mutants can be determined in Gm. However, comparison of mutant phenotypes in Gmagainst conventional models must consider the limitations of innate immunity. Our findings indicate that Gmwill be a practical, valuable, and advantageous additional model to be used alongside existing models to advance tuberculosis research.

Published
2022
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34. HylS’, a fragment of truncated hyaluronidase of <italic>streptococcus suis</italic>, contributes to immune evasion by interaction with host complement factor C3b.

Author

Xu, Jiajia, Chen, Long, Pang, Siqi, Zhang, Qiuhong, Deng, Simin, Zhu, Jiaqi, Chen, Xiabing, Langford, Paul R, Huang, Qi, Zhou, Rui, and Li, Lu

Abstract

Pathogenic bacteria have evolved many strategies to evade surveillance and attack by complements. Streptococcus suis is an important zoonotic pathogen that infects humans and pigs. Hyaluronidase (HylA) has been reported to be a potential virulence factor of S. suis. However, in this study, it was discovered that the genomic region encoding HylA of the virulent S. suis strain SC19 and other ST1 strains was truncated into four fragments when aligned with a strain containing intact HylA and possessing hyaluronidase activity. As a result, SC19 had no hyaluronidase activity, but one truncated HylA fragment, designated as HylS,’ directly interacted with complement C3b, as confirmed by western ligand blotting, pull-down, and ELISA assays. The deposition of C3b and membrane attack complex (MAC) formation on the surface of a HylS’-deleted mutant (ΔhylS’) was significantly increased compared to wild-type SC19. In human sera and whole blood, ΔhylS’ survival was significantly reduced compared to that in SC19. The resistance of ΔhylS’ to macrophages and human polymorphonuclear neutrophil PMNs also decreased. In a mouse infection model, ΔhylS’ showed reduced lethality and lower bacterial load in the organs compared to that of SC19. We conclude that the truncated hyaluronidase HylS’ fragment contributes to complement evasion and the pathogenesis of S. suis. [ABSTRACT FROM AUTHOR]

Published
2024
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35. <italic>Galleria mellonella</italic> as an infection model for the virulent <italic>Mycobacterium tuberculosis</italic> H37Rv.

Author

Asai, Masanori, Li, Yanwen, Spiropoulos, John, Cooley, William, Everest, David J., Kendall, Sharon L., Martín, Carlos, Robertson, Brian D., Langford, Paul R., and Newton, Sandra M.

Abstract

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for more ethically acceptable, economical, and reproducible TB infection models capable of mimicking key aspects of disease. Here we demonstrate and present a basic description of how Galleria mellonella (the greater wax moth, Gm) larvae can be used as a low cost, rapid and ethically more acceptable model for TB research. This is the first study to infect Gm with the fully virulent MTB H37Rv, the most widely used strain in research. Infection of Gm with MTB resulted in a symptomatic lethal infection, the virulence of which differed from both attenuated Mycobacterium bovis BCG and auxotrophic MTB strains. The Gm-MTB model can also be used for anti-TB drug screening, although CFU enumeration from Gm is necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of MTB isogenic mutants can be determined in Gm. However, comparison of mutant phenotypes in Gm against conventional models must consider the limitations of innate immunity. Our findings indicate that Gm will be a practical, valuable and advantageous additional model to be used alongside existing models to advance tuberculosis research. [ABSTRACT FROM AUTHOR]

Published
2022
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36. Identification of FtpA, a Dps-Like Protein Involved in Anti-Oxidative Stress and Virulence in Actinobacillus pleuropneumoniae.

Author

Hao Tang, Qiuhong Zhang, Weiyao Han, Zhenyue Wang, Siqi Pang, Han Zhu, Kangning Tan, Xiao Liu, Langford, Paul R., Qi Huang, Rui Zhou, and Lu Li

Abstract

Bacteria have evolved a variety of enzymes to eliminate endogenous or host-derived oxidative stress factors. The Dps protein, first identified in Escherichia coli, contains a ferroxidase center, and protects bacteria from reactive oxygen species damage. Little is known of the role of Dps-like proteins in bacterial pathogenesis. Actinobacillus pleuropneumoniae causes pleuropneumonia, a respiratory disease of swine. The A. pleuropneumoniae ftpA gene is upregulated during shifts to anaerobiosis, in biofilms and, as found in this study, in the presence of H2O2. An A. pleuropneumoniae ftpA deletion mutant (Î"ftpA) had increased H2O2 sensitivity, decreased intracellular viability in macrophages, and decreased virulence in a mouse infection model. Expression of ftpA in an E. coli dps mutant restored wild-type H2O2 resistance. FtpA possesses a conserved ferritin domain containing a ferroxidase site. Recombinant rFtpA bound and oxidized Fe2+ reversibly. Under aerobic conditions, the viability of an Î"ftpA mutant was reduced compared with the wild-type strain after extended culture, upon transition from anaerobic to aerobic conditions, and upon supplementation with Fenton reaction substrates. Under anaerobic conditions, the addition of H2O2 resulted in a more severe growth defect of Î"ftpA than it did under aerobic conditions. Therefore, by oxidizing and mineralizing Fe2+, FtpA alleviates the oxidative damage mediated by intracellular Fenton reactions. Furthermore, by mutational analysis, two residues were confirmed to be critical for Fe2+ binding and oxidization, as well as for A. pleuropneumoniae H2O2 resistance. Taken together, the results of this study demonstrate that A. pleuropneumoniae FtpA is a Dps-like protein, playing critical roles in oxidative stress resistance and virulence. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Spatial proximity and gene function: a new dimension in prokaryotic gene association network analysis with 3D-GeneNet.

Author

Gao Y, Ma B, Xu Q, Peng Y, Gong H, Guan A, Hua K, Langford PR, Jin H, and Luo R

Subjects
Algorithms, Computational Biology methods, High-Throughput Nucleotide Sequencing methods, Escherichia coli K12 genetics, Escherichia coli K12 metabolism, Escherichia coli genetics, Escherichia coli metabolism, Gene Regulatory Networks, Software
Abstract

Understanding the biological functions and processes of genes, particularly those not yet characterized, is crucial for advancing molecular biology and identifying therapeutic targets. The hypothesis guiding this study is that the 3D proximity of genes correlates with their functional interactions and relevance in prokaryotes. We introduced 3D-GeneNet, an innovative software tool that utilizes high-throughput sequencing data from chromosome conformation capture techniques and integrates topological metrics to construct gene association networks. Through a series of comparative analyses focused on spatial versus linear distances, we explored various dimensions such as topological structure, functional enrichment levels, distribution patterns of linear distances among gene pairs, and the area under the receiver operating characteristic curve by utilizing model organism Escherichia coli K-12. Furthermore, 3D-GeneNet was shown to maintain good accuracy compared to multiple algorithms (neighbourhood, co-occurrence, coexpression, and fusion) across multiple bacteria, including E. coli, Brucella abortus, and Vibrio cholerae. In addition, the accuracy of 3D-GeneNet's prediction of long-distance gene interactions was identified by bacterial two-hybrid assays on E. coli K-12 MG1655, where 3D-GeneNet not only increased the accuracy of linear genomic distance tripled but also achieved 60% accuracy by running alone. Finally, it can be concluded that the applicability of 3D-GeneNet will extend to various bacterial forms, including Gram-negative, Gram-positive, single-, and multi-chromosomal bacteria through Hi-C sequencing and analysis. Such findings highlight the broad applicability and significant promise of this method in the realm of gene association network. 3D-GeneNet is freely accessible at https://github.com/gaoyuanccc/3D-GeneNet., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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38. Bolaamphiphile Analogues of 12-bis-THA Cl 2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens.

Author

Di Blasio S, Clarke M, Hind CK, Asai M, Laurence L, Benvenuti A, Hassan M, Semenya D, Man DK, Horrocks V, Manzo G, Van Der Lith S, Lam C, Gentile E, Annette C, Bosse J, Li Y, Panaretou B, Langford PR, Robertson BD, Lam JKW, Sutton JM, McArthur M, and Mason AJ

Subjects
Animals, Female, Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, DNA, Methicillin-Resistant Staphylococcus aureus, Arthroplasty, Replacement, Hip, Anti-Infective Agents, Moths
Abstract

12-Bis-THA Cl 2 [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl 2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro , but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications. IMPORTANCE While we face an acute threat from antibiotic resistant bacteria and a lack of new classes of antibiotic, there are many effective antimicrobials which have limited application due to concerns regarding their toxicity and which could be more useful if such risks are reduced or eliminated. We modified a bolalipid antiseptic used in throat lozenges to see if it could be made more effective against some of the highest-priority bacteria and less toxic. We found that structural modifications that rendered the lipid more toxic against human cells made it less toxic in infection models and we could effectively treat caterpillars infected with either Mycobacterium tuberculosis, methicillin resistant Staphylococcus aureus, or Acinetobacter baumannii. The study provides a rationale for further adaptation toward diversifying the range of indications in which this class of antimicrobial may be used.

Published
2023
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39. Complete genome for Actinobacillus pleuropneumoniae serovar 8 reference strain 405: comparative analysis with draft genomes for different laboratory stock cultures indicates little genetic variation.

Author

Bossé JT, Li Y, Cohen LM, Stegger M, Angen Ø, Lacouture S, Gottschalk M, Lei L, Koene M, Kuhnert P, Bandara AB, Inzana TJ, Holden MTG, Harris D, Oshota O, Maskell DJ, Tucker AW, Wren BW, Rycroft AN, Langford PR, and On Behalf Of The BRaDP T Consortium

Subjects
Animals, Genetic Variation, Genome, Bacterial, High-Throughput Nucleotide Sequencing, Serogroup, Swine, Actinobacillus Infections, Actinobacillus pleuropneumoniae classification, Actinobacillus pleuropneumoniae genetics, Swine Diseases
Abstract

We report here the complete genome sequence of the widely studied Actinobacillus pleuropneumoniae serovar 8 reference strain 405, generated using the Pacific Biosciences (PacBio) RS II platform. Furthermore, we compared draft sequences generated by Illumina sequencing of six stocks of this strain, including the same original stock used to generate the PacBio sequence, held in different countries and found little genetic variation, with only three SNPs identified, all within the degS gene. However, sequences of two small plasmids, pARD3079 and p405tetH, detected by Illumina sequencing of the draft genomes were not identified in the PacBio sequence of the reference strain.

Published
2021
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40. Rapid Detection and Typing of Actinobacillus pleuropneumoniae Serovars Directly From Clinical Samples: Combining FTA ® Card Technology With Multiplex PCR.

Author

Stringer OW, Bossé JT, Lacouture S, Gottschalk M, Fodor L, Angen Ø, Velazquez E, Penny P, Lei L, Langford PR, and Li Y

Abstract

Actinobacillus pleuropneumoniae (APP), the causative agent of porcine pleuropneumonia, is highly contagious and responsible for high morbidity, mortality, and economic losses in the swine industry worldwide, but quick serotyping and diagnosis are still not widely available. In this study, we sought to validate the use of Whatman FTA ® cards for collection and processing of A. pleuropneumoniae isolates, or porcine lung tissue samples, for direct use in diagnostic multiplex PCRs. We have optimized the processing of 3-mm discs punched from FTA ® cards loaded with cultured A. pleuropneumoniae , or imprinted on lesioned regions of lung tissue, with only three distilled water washes before addition into our APP-multiplex PCR (mPCR) assay for rapid, low-cost identification and serotyping. DNA captured on FTA ® cards generated the same diagnostic PCR results as DNA extracted using commercial kits for 85 A. pleuropneumoniae clinical isolate cultures and 22 lung samples. Additionally, bacterial DNA bound to FTA ® cards was detectable by PCR after 6 months of storage at 37°C. This study provides simple, efficient, rapid, and practical sample processing for detection and molecular serotyping of A. pleuropneumoniae ., Competing Interests: EV and PP are employed by Ceva Animal Health Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stringer, Bossé, Lacouture, Gottschalk, Fodor, Angen, Velazquez, Penny, Lei, Langford and Li.)

Published
2021
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