Reuterin disruptsClostridioides difficilemetabolism and pathogenicity through reactive oxygen species generation

被引:27
作者
Engevik, Melinda A. [1 ]
Danhof, Heather A. [2 ]
Shrestha, Ritu [3 ]
Chang-Graham, Alexandra L. [2 ]
Hyser, Joseph M. [2 ]
Haag, Anthony M. [1 ,4 ]
Mohammad, Mahmoud A. [5 ]
Britton, Robert A. [2 ]
Versalovic, James [1 ,2 ,4 ]
Sorg, Joseph A. [3 ]
Spinler, Jennifer K. [1 ,4 ]
机构
[1] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
[3] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA
[4] Texas Childrens Hosp, Dept Pathol, Texas Childrens Microbiome Ctr, Houston, TX 77030 USA
[5] Baylor Coll Med, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
Reuterin; probiotics; Lactobacillus reuteri; Clostridioides difficile; enteroids; organoids; oxidative stress; reactive oxygen species; metabolism; CLOSTRIDIUM-DIFFICILE INFECTION; LACTOBACILLUS-REUTERI; OXIDATIVE STRESS; ANTIMICROBIAL RESISTANCE; HUMAN ENTEROIDS; MODEL; 3-HYDROXYPROPIONALDEHYDE; ACID; PURIFICATION; PHYSIOLOGY;
D O I
10.1080/19490976.2020.1795388
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Antibiotic resistance is one of the world's greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden.Clostridioides difficileinfection (CDI) is a prime example where adjunct probiotic therapies could decrease disease incidence through prevention. Human-derivedLactobacillus reuteriis a probiotic that produces the antimicrobial compound reuterin known to preventC. difficilecolonization of antibiotic-treated fecal microbial communities. However, the mechanism of inhibition is unclear. We show that reuterin inhibitsC. difficileoutgrowth from spores and vegetative cell growth, however, no effect onC. difficilegermination or sporulation was observed. Consistent with published studies, we found that exposure to reuterin stimulated reactive oxygen species (ROS) inC. difficile, resulting in a concentration-dependent reduction in cell viability that was rescued by the antioxidant glutathione. Sublethal concentrations of reuterin enhanced the susceptibility of vegetativeC. difficileto vancomycin and metronidazole treatment and reduced toxin synthesis byC. difficile. We also demonstrate that reuterin is protective againstC. difficiletoxin-mediated cellular damage in the human intestinal enteroid model. Overall, our results indicate that ROS are essential mediators of reuterin activity and show that reuterin production byL. reuteriis compatible as a therapeutic in a clinically relevant model.
引用
收藏
页数:21
相关论文
共 79 条
  • [11] Chinese Center for Disease Control and Prevention, 2019, SEXUALLY TRANSMITTED
  • [12] Antimicrobial resistance: a priority for global health action
    Chioro, Arthur
    Coll-Seck, Awa Marie
    Hoie, Bent
    Moeloek, Nila
    Motsoaledi, Aaron
    Rajatanavin, Rajata
    Touraine, Marisol
    [J]. BULLETIN OF THE WORLD HEALTH ORGANIZATION, 2015, 93 (07) : 439 - 439
  • [13] Intestinal Epithelial Cells In Vitro
    Chopra, Dharam P.
    Dombkowski, Alan A.
    Stemmer, Paul M.
    Parker, Graham C.
    [J]. STEM CELLS AND DEVELOPMENT, 2010, 19 (01) : 131 - 141
  • [14] Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria
    Cleusix, Valentine
    Lacroix, Christophe
    Vollenweider, Sabine
    Duboux, Marc
    Le Blay, Gwenaelle
    [J]. BMC MICROBIOLOGY, 2007, 7 (1)
  • [15] Dietary trehalose enhances virulence of epidemic Clostridium difficile
    Collins, J.
    Robinson, C.
    Danhof, H.
    Knetsch, C. W.
    van Leeuwen, H. C.
    Lawley, T. D.
    Auchtung, J. M.
    Britton, R. A.
    [J]. NATURE, 2018, 553 (7688) : 291 - +
  • [16] Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis
    Das, Nupur K.
    Schwartz, Andrew J.
    Barthel, Gabrielle
    Inohara, Naohiro
    Liu, Qing
    Sankar, Amanda
    Hill, David R.
    Ma, Xiaoya
    Lamberg, Olivia
    Schnizlein, Matthew K.
    Arques, Juan L.
    Spence, Jason R.
    Nunez, Gabriel
    Patterson, Andrew D.
    Sun, Duxin
    Young, Vincent B.
    Shah, Yatrik M.
    [J]. CELL METABOLISM, 2020, 31 (01) : 115 - +
  • [17] Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects
    Di Bella, Stefano
    Ascenzi, Paolo
    Siarakas, Steven
    Petrosillo, Nicola
    di Masi, Alessandra
    [J]. TOXINS, 2016, 8 (05):
  • [18] Reactive oxygen species: a novel antimicrobial
    Dryden, Matthew
    [J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2018, 51 (03) : 299 - 303
  • [19] Control of Clostridium difficile Physiopathology in Response to Cysteine Availability
    Dubois, Thomas
    Dancer-Thibonnier, Marie
    Monot, Marc
    Hamiot, Audrey
    Bouillaut, Laurent
    Soutourina, Olga
    Martin-Verstraete, Isabelle
    Dupuy, Bruno
    [J]. INFECTION AND IMMUNITY, 2016, 84 (08) : 2389 - 2405
  • [20] Unraveling the Physiological Complexities of Antibiotic Lethality
    Dwyer, Daniel J.
    Collins, James J.
    Walker, Graham C.
    [J]. ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55, 2015, 55 : 313 - 332