AUTHOR=Bhatt Krishna , Timsit Edouard , Rawlyk Neil , Potter Andrew , Liljebjelke Karen 

TITLE=Integrative Conjugative Element ICEHs1 Encodes for Antimicrobial Resistance and Metal Tolerance in Histophilus somni

JOURNAL=Frontiers in Veterinary Science

VOLUME=5

YEAR=2018

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2018.00153

DOI=10.3389/fvets.2018.00153

ISSN=2297-1769

ABSTRACT=<p>The objectives of this study were to determine antimicrobial resistance and metal tolerance, and identify associated genes and mobile genetic elements in clinical strains of <italic>Histophilus somni</italic> isolated from feedlot cattle in Alberta during years 2012–2016 (contemporary isolates, <italic>n</italic> = 63) and years 1980–1990 (historical isolates, <italic>n</italic> = 31). Comparison of antimicrobial resistance (AMR) showed a significant increase in resistance among contemporary isolates compared to historical isolates (<italic>P</italic> &lt; 0.001). Tolerance to copper (Cu) and zinc (Zn) concentrations above 1 mM was observed in 68 and 52% of the contemporary isolates, respectively. The <italic>tet</italic>(H) gene associated with oxytetracycline resistance and multicopper oxidase (<italic>mco</italic>) and cation efflux (<italic>czcD</italic>) genes associated with Cu and Zn tolerance were identified. An integrative conjugative element; ICE<italic>Hs1</italic>, was identified in whole genome sequences of strains resistant to oxytetracycline, which had Cu and Zn minimum inhibitory concentrations (MIC) &gt;1 mM. The length of ICE<italic>Hs1</italic> was 64,932 bp and it contained 83 genes, including tetracycline resistance gene <italic>tet</italic>H, a multidrug efflux pump gene <italic>ebrB</italic>, and metal tolerance genes <italic>mco, czcD</italic>, and <italic>acr3</italic>. Comparative genomics of ICEs revealed that ICE<italic>Hs1</italic> shares high homology with previously described ICEs of <italic>Histophilus somni, Pasteurella multocida</italic>, and <italic>Mannheimia haemolytica</italic>. The ICE<italic>Hs1</italic> is an active element capable of intra- and inter-genus transfer as demonstrated by successful transfer to <italic>H. somni</italic> and <italic>P. multocida</italic> recipients. All isolates carrying ICE<italic>Hs1</italic> were resistant to tetracycline, a commonly used antibiotic in feedlots, and had Cu and Zn MIC higher than 1 mM. Since Cu and Zn are routinely used in feedlots, there is the possibility of co-selection of AMR in <italic>H. somni</italic> due to selection pressure created by Cu and Zn. Based on results of <italic>in-vitro</italic> conjugation experiments, ICE<italic>Hs1</italic> mediated transmission of antimicrobial and metal resistance genes is possible between BRD pathogens in the respiratory tract, potentially undermining treatment options available for histophilosis and BRD.</p>