TY - JOUR
T1 - Anti-virulence strategies for Clostridioides difficile infection
T2 - advances and roadblocks
AU - Stewart, David
AU - Anwar, Farhan
AU - Vedantam, Gayatri
N1 - Funding Information:
This work was supported by funding from the National Institutes of Health [R33AI121590 (GV); R21 AI132353 (DS)], and the US Dept. of Veterans Affairs [IK6BX003789 (GV); I01BX001183 (GV)]. GV conceptualized the article, and GV, FA and DS participated in the writing of the manuscript. The Authors report no conflict of interest. We thank Adam Weiss for his patience and insight as this manuscript was being prepared.
Funding Information:
This work was supported by the National Institutes of Health [R33AI121590, R21 AI132353]; U.S. Department of Veterans Affairs [IK6BX003789, I01BX001183]. This work was supported by funding from the National Institutes of Health [R33AI121590 (GV); R21 AI132353 (DS)], and the US Dept. of Veterans Affairs [IK6BX003789 (GV); I01BX001183 (GV)]. GV conceptualized the article, and GV, FA and DS participated in the writing of the manuscript. The Authors report no conflict of interest. We thank Adam Weiss for his patience and insight as this manuscript was being prepared.
Publisher Copyright:
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/11/9
Y1 - 2020/11/9
N2 - Clostridioides difficile infection (CDI) is a common healthcare- and antibiotic-associated diarrheal disease. If mis-diagnosed, or incompletely treated, CDI can have serious, indeed fatal, consequences. The clinical and economic burden imposed by CDI is great, and the US Centers for Disease Control and Prevention has named the causative agent, C. difficile (CD), as an Urgent Threat To US healthcare. CDI is also a significant problem in the agriculture industry. Currently, there are no FDA-approved preventives for this disease, and the only approved treatments for both human and veterinary CDI involve antibiotic use, which, ironically, is associated with disease relapse and the threat of burgeoning antibiotic resistance. Research efforts in multiple laboratories have demonstrated that non-toxin factors also play key roles in CDI, and that these are critical for disease. Specifically, key CD adhesins, as well as other surface-displayed factors have been shown to be major contributors to host cell attachment, and as such, represent attractive targets for anti-CD interventions. However, research on anti-virulence approaches has been more limited, primarily due to the lack of genetic tools, and an as-yet nascent (but increasingly growing) appreciation of immunological impacts on CDI. The focus of this review is the conceptualization and development of specific anti-virulence strategies to combat CDI. Multiple laboratories are focused on this effort, and the field is now at an exciting stage with numerous products in development. Herein, however, we focus only on select technologies (Figure 1) that have advanced near, or beyond, pre-clinical testing (not those that are currently in clinical trial), and discuss roadblocks associated with their development and implementation.
AB - Clostridioides difficile infection (CDI) is a common healthcare- and antibiotic-associated diarrheal disease. If mis-diagnosed, or incompletely treated, CDI can have serious, indeed fatal, consequences. The clinical and economic burden imposed by CDI is great, and the US Centers for Disease Control and Prevention has named the causative agent, C. difficile (CD), as an Urgent Threat To US healthcare. CDI is also a significant problem in the agriculture industry. Currently, there are no FDA-approved preventives for this disease, and the only approved treatments for both human and veterinary CDI involve antibiotic use, which, ironically, is associated with disease relapse and the threat of burgeoning antibiotic resistance. Research efforts in multiple laboratories have demonstrated that non-toxin factors also play key roles in CDI, and that these are critical for disease. Specifically, key CD adhesins, as well as other surface-displayed factors have been shown to be major contributors to host cell attachment, and as such, represent attractive targets for anti-CD interventions. However, research on anti-virulence approaches has been more limited, primarily due to the lack of genetic tools, and an as-yet nascent (but increasingly growing) appreciation of immunological impacts on CDI. The focus of this review is the conceptualization and development of specific anti-virulence strategies to combat CDI. Multiple laboratories are focused on this effort, and the field is now at an exciting stage with numerous products in development. Herein, however, we focus only on select technologies (Figure 1) that have advanced near, or beyond, pre-clinical testing (not those that are currently in clinical trial), and discuss roadblocks associated with their development and implementation.
KW - Clostridioides difficile
KW - antimicrobial
KW - antisense RNA
KW - diarrhea
KW - synthetic biologic
KW - virulence
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U2 - 10.1080/19490976.2020.1802865
DO - 10.1080/19490976.2020.1802865
M3 - Review article
C2 - 33092487
AN - SCOPUS:85093820361
SN - 1949-0976
VL - 12
JO - Gut microbes
JF - Gut microbes
IS - 1
M1 - 1802865
ER -