Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are alarming in the clinical setting, as CRE isolates often exhibit resistance to most clinically-available antibiotics. Klebsiella pneumoniae carbapenemase (KPC) is the most common carbapenemase carried by CRE in North America and Europe, frequently detected in isolates of K. pneumoniae, Escherichia coli, and Enterobacter cloacae. Notably, KPC-expressing strains often arise from clonal lineages, with sequence type 258 (ST258) representing the dominant lineage in K. pneumoniae, ST131 in E. coli, and ST78 and ST171 in E. cloacae. Prior studies have demonstrated that carbapenem-resistant K. pneumoniae differs from carbapenem-susceptible K. pneumoniae at both the transcriptomic and soluble metabolomic levels. In the present study, we sought to determine whether carbapenem-resistant and carbapenem-susceptible isolates of K. pneumoniae, E. coli, and E. cloacae produce distinct volatile metabolic profiles. We were able to identify a volatile metabolic fingerprint that could discriminate between CRE and non-CRE with an area under the receiver operating characteristic curve (AUROC) as high as 0.912. Species-specific AUROCs were as high as 0.988 for K. pneumoniae and 1.000 for E. cloacae. Paradoxically, curing of KPC-expressing plasmids from a subset of K. pneumoniae isolates further accentuated the metabolic differences observed between ST258 and non-ST258.
Bibliographical noteFunding Information:
We thank Dr. Robert Bonomo, MD (Case Western Reserve University), Dr. Ilaria Frasson, PhD (University of Padova), Dr. Sara Richter, PhD (University of Padova), and Dr. Joseph D Schwartzman, MD (Geisel School of Medicine at Dartmouth) for generously providing the strains used in this study. We also thank Dr. Chris Bailey-Kellogg, PhD and Srivamshi Pittala (Dartmouth College) for their thoughtful feedback on the statistical approaches utilized. This work was supported by the National Institutes of Health grant R21 AI121076 to Jane E Hill and Lennart KA Lundblad. Dartmouth College holds an Institutional Program Unifying Population and Laboratory Based Sciences award from the Burroughs Wellcome Fund (Grant# 1014106), and both Christiaan A Rees and Mavra Nasir were supported by this grant. Christiaan A Rees was also supported by the National Institutes of Health training grant T32 LM012204 (PI: Christopher I Amos). Agnieszka Smolinska was supported by a Niels Stensen Fellowship. Alexa E Lewis and Katherine R Kane were supported by the Hellman Family Foundation at Dartmouth College. Katherine R Kane and Shannon E Kossmann were supported by the Paul K Richter and Evalyn E Cook Richter Memorial Fund at Dartmouth College.
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