Assessing correlation between antimicrobial resistance genes and susceptibility phenotypes for Enterobacter cloacae complex isolates from the Vet-LIRN AMR monitoring program and clinical samples

Project Summary Enterobacter cloacae complex (ECC) are a natural component of mammalian gastrointestinalmicrobiota (Davin-Regli and Pags 2015; Ramirez and Giron 2020) but also found in a wide range of foodsand can potentially serve as foodborne pathogens (Healy et al. 2010; Shaker et al. 2007;Capita et al. 2020;Gwida et al. 2014; Kilonzo-Nthenge et al. 2013). A recent study has identified multi-drug resistant ECC in rawtomatoes lettuce carrots and other fresh vegetables that were intended for direct human consumption inSpain (Pintor-Cora et al. 2023). ECC and E. aerogenes are recognized as the most predominant nosocomial clinical pathogens withinthe Enterobacter genus often linked to infection outbreaks (Davin-Regli and Pags 2015; Mezzatesta et al.2012). Over the past three decades they emerged as highly significant opportunistic and multi-drug resistantpathogens in hospital settings (Gaston 1988). These infections ranging from urinary tract infectionspneumonia bacteremia and sepsis pose significant risks particularly for immunocompromised individuals(Annavajhala et al. 2019; Girlich et al. 2021; Intra et al. 2023). Antimicrobial resistance (AMR) inEnterobacteriaceae represents a global public health concern (John Jr et al. 1982; Ramirez and Giron 2020).Klebsiella species and Enterobacter species including ECC isolates are recognized as the most prevalentcarbapenem-resistant Enterobacteriaceae (CRE) in the United States (Annavajhala et al. 2019; Lutgring2019; Mezzatesta et al. 2012). In recent years many antibiotics commonly used to treat Enterobacter infections including ECC-associated diseases have been alarmingly less effective(Sanders Jr and Sanders 1997). This trend isattributed to the intrinsic -lactam resistance observed in ECC species primarily due to expression of lowlevels of ampC genes encoding for an inducible AmpC-type cephalosporinase (Annavajhala et al. 2019;Seeberg et al. 1983). This unique chromosomal -lactam mechanism enables ECC species to resist thebactericidal effect of Penicillins and first- and second-generation Cephalosporins. In cases of prolongedexposure to -lactam drugs ECC species may even exhibit resistance to third generation Cephalosporins(Seeberg et al. 1983). The Vet-LIRN AMR monitoring program has collected and sequenced approximately 200 ECC strainsand determined their corresponding AMR phenotypes. KSVDL routinely receives ECC-positive diagnosticsamples. The objectives of this project are to isolate ~20 ECC isolates from KSVDL submitted specimensobtain genome sequences and determine AMR phenotypes then perform a comparative analysis of AMRphenotypes of these ECC genome sequences alongside the 200 ECC strains from the Vet-LIRN AMRmonitoring program.