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International audience; Background: Streptococcus equi subspecies equi (S.equi) is the cause of the highly contagious equine respiratory disease ‘strangles’. Approximately 10% of recovered animals can persistently carry the bacteria and transmit it to naïve animals. The global movement of horses is an ideal mechanism for widespread transmission to geographically distant locations.Objectives: Utilise whole-genome sequence data to disentangle the transmission of S. equi and subsequent outbreaks of strangles.Study design: In vitro analysis of micro-organisms.Methods: Isolates (n = 670) of S. equi were recovered from clinical samples submitted to multiple collaborating clinics and institutions globally. Following species confirmation, isolates underwent whole-genome sequencing using Illumina technology. Sequence reads passing quality control measures were assembled and uploaded to Pathogenwatch, which assigned a phylogeny based upon sequences of core genome alleles. Population structure was inferred using the population mixture analysis in BAPS.Results: BAPS clustered the isolates into six different clusters (BAPS 1-6) and showed dominant lineages in different geographical areas but also global transmission within the clusters. Sub-groups within the clusters highlighted multiple outbreaks at local, national and international scales and highlighted population structures and transmission dynamics within single locations. For example, four different strains collected over just seven months were identified in a single location. Sequence data also identified a statistically significant decline in BAPS-5 since 2010.Main limitations: Pathogenwatch has shown its utility in investigating S. equi transmission and population structure. However, it is based upon a curated set of 1286 core genome loci. Further investigations will need to be conducted using the full spectrum of data available from whole-genome sequencing.Conclusions: Pathogenwatch was used as a tool to rapidly identify and visualise the whole-genome sequence data of a large S. equi dataset. The data demonstrate widespread transmission of multiple S. equi lineages and provide strong evidence that asymptomatic carrier horses are perpetuating this dissemination.

The accurate identification of Taylorella equigenitalis strains is essential to improve worldwide prevention and control strategies for contagious equine metritis (CEM). This study compared 367 worldwide equine strains using multilocus sequence typing according to the geographical origin, isolation year and equine breed. The strains were divided into 49 sequence types (STs), including 10 described for the first time. Three major and three minor clonal complexes (CCs), and 11 singletons, were identified. The genetic heterogeneity was low (0.13 STs/strain) despite the wide diversity of geographical origins (n = 16), isolation years (1977-2018) and equine breeds (n = 18). It was highest outside Europe and in the 1977-1997 period; current major STs and CCs already existed before 1998. Previous data associated the major CC1 with the first CEM outbreaks in 1977-1978 in the United Kingdom, Australia and the United States, and revealed its circulation in France. Our study confirms its circulation in France over a longer period of time (1992-2018) and its distribution in Spain and Germany but not throughout Europe. In addition to CC1, relationships between non-European and European countries were observed only through ST4, ST17 and ST30. Within Europe, several STs emerged with cross-border circulation, in particular ST16 and ST46 from the major complexes CC2 and CC8. These results constitute a baseline for monitoring the spread of CEM outbreaks. A retrospective analysis of a higher number of strains isolated worldwide between 1977 and the early 2000s would be helpful to obtain an exhaustive picture of the original CEM situation.

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.

The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, Streptococcus equi subspecies equi, establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit S. equi to naïve animals initiating new episodes of disease. Here, we report the analysis and visualization of phylogenomic and epidemiological data for 670 isolates of S. equi recovered from 19 different countries using a new core-genome multilocus sequence typing (cgMLST) web bioresource. Genetic relationships among all 670 S. equi isolates were determined at high resolution, revealing national and international transmission events that drive this endemic disease in horse populations throughout the world. Our data argue for the recognition of the international importance of strangles by the Office International des Épizooties to highlight the health, welfare and economic cost of this disease. The Pathogenwatch cgMLST web bioresource described herein is available for tailored genomic analysis of populations of S. equi and its close relative S. equi subspecies zooepidemicus that are recovered from horses and other animals, including humans, throughout the world. This article contains data hosted by Microreact.