Transposon-associated lincosamide resistance lnu (C) gene identified in Brachyspira hyodysenteriae ST83

Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery

“…The WGS of each isolate was examined for mutations in the 16S rRNA, 23S rRNA, and rplC genes associated with resistance to these antibiotics (Table 1 ). Reduced susceptibility to tylosin, lincomycin, tylvalosin, and doxycycline (i.e., antimicrobial phenotype) correlated well with the presence of relevant mutant SNPs (i.e., genotype), giving good (≥80%) sensitivity, specificity, positive predictive values, and negative predictive values, as calculated using two-by-two table analysis (Table S3 ) (Mackinnon, 2000 ), in accordance with previous studies (Karlsson et al, 1999 , 2003 ; Pringle et al, 2007 ; Hidalgo et al, 2011 ; Alvarez-Ordóñez et al, 2013 ; Mahu et al, 2017 ; De Luca et al, 2018 ). A new polymorphism (G1058T) associated with reduced doxycycline susceptibility was identified in the 16S rRNA gene of isolates BH6 and BH37.…”

“…The 34 UK B. hyodysenteriae isolates sequenced for this study were obtained from submissions to APHA between 2005 and 2013, except P18A which was a historical UK strain isolated from a pig with swine dysentery in the late 1970s (Lemcke and Burrows, 1981 ; Table 1 ). The genome properties of these isolates, including genome size, GC%, and number of predicted coding sequences were similar to the reference strain WA1 (Bellgard et al, 2009 ) and other published B. hyodysenteriae genomes (Black et al, 2015 ; La et al, 2016b ; De Luca et al, 2018 ; Table S1 ). As only 43 B. hyodysenteriae genomes have been published to date, the B. hyodysenteriae MLST scheme (La et al, 2009 ) was used to place these UK isolates into a global context.…”

“…A maximum likelihood phylogenetic tree was constructed using core genome SNPs from the WGS of the 34 UK isolates and 43 published B. hyodysenteriae genomes (Bellgard et al, 2009 ; Black et al, 2015 ; La et al, 2016b ; De Luca et al, 2018 ; Figure 1 ). Most UK isolates from this study ( n = 32) formed a sub-cluster that also contained isolates from Germany and the Canadian ST4 isolate.…”

“…A major threat to the effective control of SD is resistance of B. hyodysenteriae to pleuromutilins and/or other antibiotics, indeed isolates with reduced susceptibility have been reported in North America, Europe, Japan, and Australia, and the prevalence of resistance appears to be increasing (Karlsson et al, 2002 ; Lobová et al, 2004 ; Hidalgo et al, 2009 ; Pringle et al, 2012 ; Swedres-Svarm, 2015 ; Kajiwara et al, 2016 ; Mirajkar et al, 2016 ; Mahu et al, 2017 ; De Luca et al, 2018 ). Reduced antibiotic susceptibility can lead to suboptimal or ineffective antibiotic treatment, resulting in increased economic impact to producers, adverse effects on pig health and welfare, and development of antibiotic resistance.…”

“…Furthermore, multidrug resistance has been reported and in some herds B. hyodysenteriae has become resistant to all authorised antimicrobials, leaving depopulation and elimination of infection through thorough cleansing and disinfection, and then restocking as the only effective course of action (Hampson, 2012 ; Strugnell et al, 2013 ), which has significant cost. Reduced antibiotic susceptibility in B. hyodysenteriae has been associated with the presence of lnu (C) (lincosamides) (De Luca et al, 2018 ) and point mutations at specific positions in the 16S rRNA gene (doxycycline), 23S rRNA gene (macrolides, lincosamides, and pleuromutilins) and rplC , the gene encoding the L3 ribosomal protein (pleuromutilins) (Karlsson et al, 1999 ; Pringle et al, 2004 , 2007 ; Hidalgo et al, 2011 ; Hillen et al, 2014 ; De Luca et al, 2018 ). The development of resistance to pleuromutilins in B. hyodysenteriae is thought to occur in a stepwise manner both in vitro and in vivo , suggesting that multiple mutations are required for the emergence of high level resistance (Karlsson et al, 2001 ; Hidalgo et al, 2011 ; van Duijkeren et al, 2014 ), however the dynamics and mechanisms of emergence of resistance to pleuromutilins remain poorly defined.…”