Community-acquired Clostridium difficile infection and Australian food animals

Squire, Michele M.; Knight, Daniel R.; Riley, Thomas V.

doi:10.1071/ma15040

Cited by 6 publications

(8 citation statements)

References 38 publications

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“…difficile spores in the environment. These include curtailing the use of late-generation cephalosporins, immunization, environmental cleaning (e.g., sporicidal treatment of effluent) and discontinuing the practice of slaughtering neonatal calves (37, 50).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary and Genomic Insights into Clostridioides difficile Sequence Type 11: a Diverse Zoonotic and Antimicrobial-Resistant Lineage of Global One Health Importance

Knight

Kullin

Androga

et al. 2019

mBio

113

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Clostridioides difficile (Clostridium difficile) sequence type 11 (ST11) is well established in production animal populations worldwide and contributes considerably to the global burden of C. difficile infection (CDI) in humans. Increasing evidence of shared ancestry and genetic overlap of PCR ribotype 078 (RT078), the most common ST11 sublineage, between human and animal populations suggests that CDI may be a zoonosis. We performed whole-genome sequencing (WGS) on a collection of 207 ST11 and closely related ST258 isolates of human and veterinary/environmental origin, comprising 16 RTs collected from Australia, Asia, Europe, and North America. Core genome single nucleotide variant (SNV) analysis identified multiple intraspecies and interspecies clonal groups (isolates separated by ≤2 core genome SNVs) in all the major RT sublineages: 078, 126, 127, 033, and 288. Clonal groups comprised isolates spread across different states, countries, and continents, indicative of reciprocal long-range dissemination and possible zoonotic/anthroponotic transmission. Antimicrobial resistance genotypes and phenotypes varied across host species, geographic regions, and RTs and included macrolide/lincosamide resistance (Tn6194 [ermB]), tetracycline resistance (Tn6190 [tetM] and Tn6164 [tet44]), and fluoroquinolone resistance (gyrA/B mutations), as well as numerous aminoglycoside resistance cassettes. The population was defined by a large “open” pan-genome (10,378 genes), a remarkably small core genome of 2,058 genes (only 19.8% of the gene pool), and an accessory genome containing a large and diverse collection of important prophages of the Siphoviridae and Myoviridae. This study provides novel insights into strain relatedness and genetic variability of C. difficile ST11, a lineage of global One Health importance. IMPORTANCE Historically, Clostridioides difficile (Clostridium difficile) has been associated with life-threatening diarrhea in hospitalized patients. Increasing rates of C. difficile infection (CDI) in the community suggest exposure to C. difficile reservoirs outside the hospital, including animals, the environment, or food. C. difficile sequence type 11 (ST11) is known to infect/colonize livestock worldwide and comprises multiple ribotypes, many of which cause disease in humans, suggesting CDI may be a zoonosis. Using high-resolution genomics, we investigated the evolution and zoonotic potential of ST11 and a new closely related ST258 lineage sourced from diverse origins. We found multiple intra- and interspecies clonal transmission events in all ribotype sublineages. Clones were spread across multiple continents, often without any health care association, indicative of zoonotic/anthroponotic long-range dissemination in the community. ST11 possesses a massive pan-genome and numerous clinically important antimicrobial resistance elements and prophages, which likely contribute to the success of this globally disseminated lineage of One Health importance.

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Section: Discussionmentioning

confidence: 99%

Evolutionary and Genomic Insights into Clostridioides difficile Sequence Type 11: a Diverse Zoonotic and Antimicrobial-Resistant Lineage of Global One Health Importance

Knight

Kullin

Androga

et al. 2019

mBio

113

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“…We have previously reported that RT014 has established significant reservoirs in both human and porcine populations in Australia (Foster et al, 2014; Knight et al, 2014, 2015b; Collins et al, in press). These findings, together with a notable increase in CA-CDI in Australia, particularly in populations not considered to be at risk of CDI, have fuelled speculation that zoonotic transmission is a potential source of human infection (Slimings et al, 2014; Squire et al, 2015; Bloomfield and Riley, 2016). Using WGS and high-resolution core genome phylogenetics we describe for the first time the evolutionary relationships and extent of genetic overlap between strains of RT014 sourced from human and pigs in Australia.…”

Section: Discussionmentioning

confidence: 99%

“…Within Australia, two livestock/agricultural practices have been identified which could present significant risk for CA-CDI: (i) slaughtering of neonatal animals destined for human consumption, and (ii) the recycling of effluent to agriculture and compost manufacture with dissemination of contaminated vegetables and compost in the community setting (Squire and Riley, 2013; Squire et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

“…Possible reservoirs of CDI external to the healthcare system include wild animals, domesticated animals, performance animals, food, water, soil, farm animals, and their effluent or effluent by-products including compost (Hensgens et al, 2012; Squire et al, 2015; Bloomfield and Riley, 2016). C. difficile is particularly prevalent in production animals such as piglets and calves both in Australia (Knight et al, 2014, 2016) and other countries (Hensgens et al, 2012; Rodriguez et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Genome Analysis of Clostridium difficile PCR Ribotype 014 Lineage in Australian Pigs and Humans Reveals a Diverse Genetic Repertoire and Signatures of Long-Range Interspecies Transmission

et al. 2017

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Clostridium difficile PCR ribotype (RT) 014 is well-established in both human and porcine populations in Australia, raising the possibility that C. difficile infection (CDI) may have a zoonotic or foodborne etiology. Here, whole genome sequencing and high-resolution core genome phylogenetics were performed on a contemporaneous collection of 40 Australian RT014 isolates of human and porcine origin. Phylogenies based on MLST (7 loci, STs 2, 13, and 49) and core orthologous genes (1260 loci) showed clustering of human and porcine strains indicative of very recent shared ancestry. Core genome single nucleotide variant (SNV) analysis found 42% of human strains showed a clonal relationship (separated by ≤2 SNVs in their core genome) with one or more porcine strains, consistent with recent inter-host transmission. Clones were spread over a vast geographic area with 50% of the human cases occurring without recent healthcare exposure. These findings suggest a persistent community reservoir with long-range dissemination, potentially due to agricultural recycling of piggery effluent. We also provide the first pan-genome analysis for this lineage, characterizing its resistome, prophage content, and in silico virulence potential. The RT014 is defined by a large “open” pan-genome (7587 genes) comprising a core genome of 2296 genes (30.3% of the total gene repertoire) and an accessory genome of 5291 genes. Antimicrobial resistance genotypes and phenotypes varied across host populations and ST lineages and were characterized by resistance to tetracycline [tetM, tetA(P), tetB(P) and tetW], clindamycin/erythromycin (ermB), and aminoglycosides (aph3-III-Sat4A-ant6-Ia). Resistance was mediated by clinically important mobile genetic elements, most notably Tn6194 (harboring ermB) and a novel variant of Tn5397 (harboring tetM). Numerous clinically important prophages (Siphoviridae and Myoviridae) were identified as well as an uncommon accessory gene regulator locus (agr3). Conservation in the pathogenicity locus and S-layer correlated with ST affiliation, further extending the concept of clonal C. difficile lineages. This study provides novel insights on the genetic variability and strain relatedness of C. difficile RT014, a lineage of emerging One Health importance. Ongoing molecular and genomic surveillance of strains in humans, animals, food, and the environment is imperative to identify opportunities to reduce the overall CDI burden.

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“…Individuals acquiring disease in the community setting do not have the classic risk factors for CDI acquisition and are generally young and healthy, without contact with hospital- ized patients and often without prior antimicrobial exposure (173)(174)(175). Notably, the genotypes of C. difficile strains acquired in the community differ from those of predominant hospital strains.…”

Section: Animal Reservoirs and Zoonotic Potentialmentioning

confidence: 99%

Diversity and Evolution in the Genome of Clostridium difficile

et al. 2015

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SUMMARY Clostridium difficile infection (CDI) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. In the last 2 decades, PCR- and sequence-based techniques, particularly whole-genome sequencing (WGS), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. C. difficile is taxonomically distinct from many other well-known clostridia, with a diverse population structure comprising hundreds of strain types spread across at least 6 phylogenetic clades. The C. difficile species is defined by a large diverse pangenome with extreme levels of evolutionary plasticity that has been shaped over long time periods by gene flux and recombination, often between divergent lineages. These evolutionary events are in response to environmental and anthropogenic activities and have led to the rapid emergence and worldwide dissemination of virulent clonal lineages. Moreover, genome analysis of large clinically relevant data sets has improved our understanding of CDI outbreaks, transmission, and recurrence. The epidemiology of CDI has changed dramatically over the last 15 years, and CDI may have a foodborne or zoonotic etiology. The WGS era promises to continue to redefine our view of this significant pathogen.

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Community-acquired Clostridium difficile infection and Australian food animals

Cited by 6 publications

References 38 publications

Evolutionary and Genomic Insights into Clostridioides difficile Sequence Type 11: a Diverse Zoonotic and Antimicrobial-Resistant Lineage of Global One Health Importance

Evolutionary and Genomic Insights into Clostridioides difficile Sequence Type 11: a Diverse Zoonotic and Antimicrobial-Resistant Lineage of Global One Health Importance

Genome Analysis of Clostridium difficile PCR Ribotype 014 Lineage in Australian Pigs and Humans Reveals a Diverse Genetic Repertoire and Signatures of Long-Range Interspecies Transmission

Diversity and Evolution in the Genome of Clostridium difficile

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