Petersson M, Pettersen JS, Henriksen HB, Duzs Á, Fernández-Quintero ML, Burlet NJ, Mojica N, Krengel U, Jenkins TP, Ward AB, Andersen TE, Møller-Jensen J, Gram L, Laustsen AH, Thrane SW.
Gut Microbes
Dec. 31, 2026
Bacterial enteric pathogens are major contributors to the global burden of diarrheal diseases and the associated consequences for human health including malnutrition, growth stunting, morbidity, and mortality. While mortality from diarrhea has decreased, incidence remains high, and better interventions for preventing disease are needed. Single-domain antibodies (i.e., VHHs), functioning as target-binding proteins in the gastrointestinal tract, have been proposed as a potential approach to mitigate bacterial pathogenesis. Here, we describe a mitigation strategy where precision binding of a bivalent VHH to the receptor-binding B-pentamer of heat-labile enterotoxin aggregates the AB5 toxin and impairs enterotoxigenic Escherichia coli colonization in a flow chamber model simulating the human intestine. The VHH construct also binds to the structurally similar cholera toxin and effectively abrogates its intestinal cell cytotoxicity in vitro. Based on these results, we believe that targeting virulence could emerge as a new strategy for the management of bacterial enteric pathogens, supporting gut health in at-risk populations alongside vaccination campaigns or in populations without access to vaccines.
Park J, Jo G, Reyes Y, Pickens W, Kim DS, Beaver A, Costantini VP, Liu C, Kim D, Park D, Longo V, Brewer-Jensen PD, Mallory ML, Satterwhite E, Zapata-Bustos R, Marchioni J, Zweigart MR, Flitter BA, Vinjé J, Han J, Ross TM, Lee J, Lavinder JJ, Tucker SN, Ke Z, Ward AB, Lindesmith LC, Baric RS, Georgiou G.
Erasmus MF, Bedinger D, Hopkins E, Ferguson G, Strickler J, Graff CP, Summers SR, Capehart SL, Slocum JD, Richardson C, Kumar S, Sun Z, Shang Y, Zhang J, Gu M, Yi L, Wellner A, Zheng S, Lu W, Sormanni P, Greenig M, Zhang H, Mann BT, Baghbanzadeh M, Rahnavard A, Moore GL, Sun H, Ding Y, Nisthal A, Kanodia J, Bernett MJ, Pélissier A, Shao Y, Rodriguez Martinez M, Ramesh K, Nastri H, Evers A, Abdelatif A, Bordner AJ, Bordyuh M, Heo L, Kidd BA, Serhat Tetikol H, Wei S, Shin JE, Peckner R, Manley L, Lunge A, Devasurmutt Y, Guloglu B, Copoiu L, McGibbon M, Fernandez-Quintero ML, Mishra N, Callaghan SM, Swanson OM, Bader DLV, Ferguson JA, Raghavan SSR, Nemoz B, Maillie CA, Bowman C, Briney B, Ward AB, Marcatili P, Akbar R, He B, Wu F, Yao J, Hu B, Kucer M, Gibson KR, Somasundaram R, Hung LW, Kaszuba T, Fremont DH, Jeong H, Kurella VB, Malhotra S, Kumar S, Liu Y, Xu L, Misa J, John ANS, Vogt J, Dávila-Hernández FA, Xu D, Chungyoun M, Huggan ZD, Gray JJ, Parkinson J, Ko YS, Wang W, Geiger F, Ziegler JD, Haas N, Challacombe C, Qamar A, Singh A, Tang YC, An Z, Jiang X, Kim Y, Zhao X, Swanson E, Klattig J, Winkler K, Bataa T, Sandig V, Denzler L, Liu C, Brezski RJ, Spector L, Perea-Schmittle K, D'Angelo S, Ferrara F, Bradbury ARM.
Williams BG, Barrett JR, Scott JB, Rigby CA, Cagiada M, Quinkert D, McHugh K, Huhn A, Burnap SA, Gourjault C, Byrne F, Raghavan SSR, Rodrigues A, Bergamaschi L, Balzarotti B, Watson S, Miller N, King LDW, Donnellan FR, Gladstone CA, Paterson J, Scalabrino S, Silk SE, Salkeld J, Minassian AM, Skinner K, Struwe WB, Deane CM, Reece ST, Ward AB, Draper SJ.
Zhou P, Feng Z, He WT, Zhu Y, Yuan M, Li X, Zhang Y, Vo L, Capozzola T, Callaghan S, Mishra N, Avillion G, Dueker K, Liang B, Roy Chowdhury R, Nedellec R, Lee WH, Allen JD, Walsh A, Melo M, McAnarney ET, Kumar NA, Rinaldi W, Ferguson M, Crispin MM, Ward AB, Irvine DJ, Alameh MG, Weissman D, Baric RS, Gralinski LE, Wilson IA, Burton DR, Andrabi R.
Lin HK, Blake DA, Freeman R, Chen Y, Kim J, Johnson AM, Wells K, Mudigonda A, Liu W, Yadav P, Zeng F, Muhuri A, Min K, Sarkar S, Wang Y, Goyal S, Roberts RC, Christensen E, Ward AB, Heller B, Chun P, Dougan J, Porter CC, Barwick BG, Paulos CM, Yang L, Patgiri A, Thomas SN, Waller EK, Rafiq S.
Naghizadeh M, Flores-Garcia Y, Moskovitz R, Erdogan SM, Martin GM, Ofori EA, Plieskatt J, Cannac F, MacGill RS, Nielsen MA, Locke E, King CR, Miura K, Birkett A, Soisson LA, Sander AF, Skogstrand K, Barfod L, Salgado-Jimenez B, Borbye-Lorenzen N, Wilson IA, Ward AB, Zavala F, Theisen M.
Dueker K, Capozzola T, Feng Z, Lin RN, Hurtado J, Bangaru S, Yuan M, Beutler N, Garcia E, He WT, Callaghan S, Avillion G, Vo L, Li X, Torres JL, Musharrafieh R, Song G, Mishra N, Sharma P, Yong P, Anzanello F, Kaczmarek Michaels K, Ben-Akiva E, Silva M, Melo M, Makhdoomi M, Westfall-Gomez E, Rinaldi W, Ferguson M, Safonova Y, Crotty S, Irvine DJ, Rogers T, Ward AB, Briney B, Wilson IA, Burton DR, Andrabi R.
Skelly AN, Fan C, Keeffe JR, Ökten AB, Gavor E, Newby ML, Allen JD, Kreider EF, Ding W, Osbaldeston RA, Park Y, Connell AJ, Lituchy MG, Bibollet-Ruche F, Radford KM, P West A Jr, Peña-Hernández MA, Cruickshank K, Liu W, Li Y, Albertus A, McWilliams B, Russell RM, Konrath KM, Torres JL, Yuan M, Gao H, Montefiori DC, Saag MS, Goepfert PA, Kulp DW, Ward AB, Wilson IA, Shaw GM, Andrabi R, Crispin M, Weissman D, Wilen CB, Bjorkman PJ, Hahn BH.