title: An in vitro combined antibiotic-antibody treatment eliminates toxicity from Shiga toxin-producing Escherichia coli.
abstract: Treating Shiga toxin-producing Escherichia coli (STEC) gastrointestinal infections is difficult. The utility of antibiotics for STEC treatment is controversial, since antibiotic resistance among STEC isolates is widespread and certain antibiotics dramatically increase the expression of Shiga toxins (Stxs), which are some of the most important virulence factors in STEC. Stxs contribute to life-threatening hemolytic uremic syndrome (HUS), which develops in considerable proportions of patients with STEC infections. Understanding the antibiotic resistance profiles of STEC isolates and the Stx induction potential of promising antibiotics is essential for evaluating any antibiotic treatment of STEC. In this study, 42 O157:H7 or non-O157 STEC isolates (including the "big six" serotypes) were evaluated for their resistance against 22 antibiotics by using an antibiotic array. Tigecycline inhibited the growth of all of the tested STEC isolates and also inhibited the production of Stxs (Stx2 in particular). In combination with neutralizing antibodies to Stx1 and Stx2, the tigecycline-antibody treatment fully protected Vero cells from Stx toxicity, even when the STEC bacteria and the Vero cells were cultured together. The combination of an antibiotic such as tigecycline with neutralizing antibodies presents a promising strategy for future STEC treatments.
authors.affiliation: Western Regional Research Center, U.S. Department of Agriculture, Agricultural Research Service, Albany, California, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Skinner
authors.affiliation: Center for Food Safety and Applied Nutrition, Food and Drug Administration, Division of Microbiology, College Park, Maryland, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Western Regional Research Center, U.S. Department of Agriculture, Agricultural Research Service, Albany, California, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Patfield
authors.affiliation: Western Regional Research Center, U.S. Department of Agriculture, Agricultural Research Service, Albany, California, USA xiaohua.he@ars.usda.gov.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D000906:Antibodies / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D007779:Lactobacillus acidophilus / Q000502:physiology; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D054323:Shiga-Toxigenic Escherichia coli / Q000187:drug effects*; D000078304:Tigecycline; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D000906:Antibodies; D057134:Antibodies, Neutralizing; D000078304:Tigecycline; D008911:Minocycline