AUTHOR=Yao Yancheng , Doijad Swapnil , Falgenhauer Jane , Schmiedel Judith , Imirzalioglu Can , Chakraborty Trinad 

TITLE=Co-occurrence of dual carbapenemases KPC-2 and OXA-48 with the mobile colistin resistance gene mcr-9.1 in Enterobacter xiangfangensis

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.2022.960892

DOI=10.3389/fcimb.2022.960892

ISSN=2235-2988

ABSTRACT=<p>Bacterial infections with the genus <italic>Enterobacter</italic> are notoriously difficult to treat and often associated with resistance to penicillin, aminoglycosides, fluoroquinolones, and third-generation cephalosporins. Also, <italic>Enterobacter</italic> species have emerged as the third most common hosts for carbapenemases worldwide, forcing the use of colistin as a “last-resort” antibiotic for the treatment. Studies on the population structure of the genus <italic>Enterobacter</italic> repeatedly detect <italic>E. xiangfangensis</italic> as a common clinical species present worldwide. Here, we report on the characteristics of an extreme drug-resistant <italic>E. xiangfangensis</italic> isolate va18651 (ST88), obtained from a cervical swab of an expectant mother. The isolate was resistant to almost all the classes of antibiotics tested, including β-lactams (viz., penicillins, carbapenems, cephalosporin, monobactams, and their combinations), quinolone, aminoglycosides, and sulfonamide/dihydrofolate reductase inhibitor, and exhibited heteroresistance towards colistin. Analysis of its complete genome sequence revealed 37 antibiotic resistance genes (ARGs), including <italic>mcr-9.1</italic>, <italic>bla<sub>KPC-2</sub></italic>, and <italic>bla<sub>OXA-48</sub></italic>, encoded on three of the four different plasmids (cumulative plasmidome size 604,632 bp). An unusually high number of plasmid-based heavy metal resistance gene (HRG) clusters towards silver, arsenate, cadmium, copper, mercury, and tellurite were also detected. Virulence genes (VGs) for the lipopolysaccharide and capsular polysaccharide structures, iron acquisition (<italic>iroBCDEN</italic>, <italic>ent/fep/fes</italic>, <italic>sitABCD</italic>, <italic>iut</italic>, and <italic>fur</italic>), and a type VI secretion system, together with motility genes and Type IV pili, were encoded chromosomally. Thus, a unique combination of chromosomally encoded VGs, together with plasmid-encoded ARGs and HRGs, converged to result in an extreme drug-resistant, pathogenic isolate with survival potential in environmental settings. The use of a disinfectant, octenidine, led to its eradication; however, the existence of a highly antibiotic-resistant isolate with significant virulence potential is a matter of concern in public health settings and warrants further surveillance for extreme drug-resistant <italic>Enterobacter</italic> isolates.</p>