Eyre, David W., Didelot, Xavier, Buckley, Anthony M., Freeman, Jane, Moura, Ines B., Crook, Derrick W., Peto, Tim E.A., Walker, A. Sarah, Wilcox, Mark H. and Dingle, Kate E. (2019) Clostridium difficile trehalose metabolism variants are common and not associated with adverse patient outcomes when variably present in the same lineage. EBioMedicine, 43 . pp. 347-355. doi:10.1016/j.ebiom.2019.04.038 ISSN 2352-3964.

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Abstract

Background: Clostridium difficile ribotype-027, ribotype-078, and ribotype-017 are virulent and epidemic lineages. Trehalose metabolism variants in these ribotypes, combined with increased human trehalose consumption, have been hypothesised to have contributed to their emergence and virulence.

Methods: 5232 previously whole-genome sequenced C. difficile isolates were analysed. Clinical isolates were used to investigate the impact of trehalose metabolism variants on mortality. Import data were used to estimate changes in dietary trehalose. Ribotype-027 virulence was investigated in a clinically reflective gut model.

Findings: Trehalose metabolism variants found in ribotype-027 and ribotype-017 were widely distributed throughout C. difficile clade-2 and clade-4 in 24/29 (83%) and 10/11 (91%) of sequence types (STs), respectively. The four-gene trehalose metabolism cluster described in ribotype-078 was common in genomes from all five clinically-important C. difficile clades (40/167 [24%] STs).

The four-gene cluster was variably present in 208 ribotype-015 infections (98 [47%]); 27/208 (13%) of these patients died within 30-days of diagnosis. Adjusting for age, sex, and infecting ST, there was no association between 30-day all-cause mortality and the four-gene cluster (OR 0.36 [95%CI 0.09–1.34, p = 0.13]).

Synthetic trehalose imports in the USA, UK, Germany and the EU were  < 1 g/capita/year during 2000–2006, and  < 9 g/capita/year 2007–2012, compared with dietary trehalose from natural sources of ~100 g/capita/year.

Trehalose supplementation did not increase ribotype-027 virulence in a clinically-validated gut model.

Interpretation: Trehalose metabolism variants are common in C. difficile. Increases in total dietary trehalose during the early-mid 2000s C. difficile epidemic were likely relatively minimal. Alternative explanations are required to explain why ribotype-027, ribotype-078 and ribotype-017 have been successful.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Clostridium difficile -- Genetics
Journal or Publication Title:	EBioMedicine
Publisher:	Elsevier BV
ISSN:	2352-3964
Official Date:	May 2019
Dates:	Date Event May 2019 Published 26 April 2019 Available 18 April 2019 Accepted
Volume:	43
Page Range:	pp. 347-355
DOI:	10.1016/j.ebiom.2019.04.038
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	8 May 2019
Date of first compliant Open Access:	9 May 2019
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED [NIHR] National Institute for Health Research http://dx.doi.org/10.13039/501100000272 UNSPECIFIED Public Health England http://dx.doi.org/10.13039/501100002141 UNSPECIFIED Big Data Institute UNSPECIFIED UNSPECIFIED Hayashibara Co. Ltd. UNSPECIFIED

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