AUTHOR=Sato Toyotaka , Harada Kazuki , Usui Masaru , Yokota Shin-ichi , Horiuchi Motohiro 

TITLE=Colistin Susceptibility in Companion Animal-Derived Escherichia coli, Klebsiella spp., and Enterobacter spp. in Japan: Frequent Isolation of Colistin-Resistant Enterobacter cloacae Complex

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.946841

DOI=10.3389/fcimb.2022.946841

ISSN=2235-2988

ABSTRACT=<p>Transmission of colistin-resistant <italic>Enterobacterales</italic> from companion animals to humans poses a clinical risk as colistin is a last-line antimicrobial agent for treatment of multidrug-resistant Gram-negative bacteria including <italic>Enterobacterales</italic>. In this study, we investigated the colistin susceptibility of 285 <italic>Enterobacterales</italic> (including 140 <italic>Escherichia coli</italic>, 86 <italic>Klebsiella</italic> spp., and 59 <italic>Enterobacter</italic> spp.) isolated from companion animals in Japan. We further characterized colistin-resistant isolates by multilocus sequence typing (MLST), phylogenetic analysis of <italic>hsp60</italic> sequences, and population analysis profiling, to evaluate the potential clinical risk of companion animal-derived colistin-resistant <italic>Enterobacterales</italic> to humans in line with the One Health approach. All <italic>E. coli</italic> isolates were susceptible to colistin, and only one <italic>Klebsiella</italic> spp. isolate (1.2%, 1/86 isolates) was colistin resistant. <italic>Enterobacter</italic> spp. isolates were frequently colistin resistant (20.3%, 12/59 isolates). In colistin-resistant <italic>Enterobacter</italic> spp., all except one isolate exhibited colistin heteroresistance by population analysis profiling. These colistin-heteroresistant isolates belonged to clusters I, II, IV, VIII, and XII based on <italic>hsp60</italic> phylogeny. MLST analysis revealed that 12 colistin-resistant <italic>Enterobacter</italic> spp. belonged to the <italic>Enterobacter cloacae</italic> complex; five <italic>Enterobacter kobei</italic> (four ST591 and one ST1577), three <italic>Enterobacter asburiae</italic> (one ST562 and two ST1578), two <italic>Enterobacter roggenkampii</italic> (ST606 and ST1576), and <italic>Enterobacter hormaechei</italic> (ST1579) and <italic>E. cloacae</italic> (ST765) (each one strain). Forty-two percent of the colistin-resistant <italic>E. cloacae</italic> complex isolates (predominantly ST562 and ST591) belonged to lineages with human clinical isolates. Four <italic>E. kobei</italic> ST591 isolates were resistant to third-generation cephalosporines, aminoglycosides, and fluroquinolones but remained susceptible to carbapenems. In conclusion, our study is the first to our knowledge to report the frequent isolation of the colistin-resistant <italic>E. cloacae</italic> complex from companion animals. Furthermore, a subset of isolates belonged to human-associated lineages with resistance to multiple classes of antibiotics. These data warrant monitoring carriage of the colistin-resistant <italic>E. cloacae</italic> complex in companion animals as part of a domestic infection control procedure in line with the One Health approach.</p>