AUTHOR=Knecht Camila A. , García Allende Natalia , Álvarez Verónica E. , Prack McCormick Barbara , Massó Mariana G. , Piekar María , Campos Josefina , Fox Bárbara , Camicia Gabriela , Gambino Anahí S. , Leguina Ana Carolina del Valle , Donis Nicolás , Fernández-Canigia Liliana , Quiroga María Paula , Centrón Daniela 

TITLE=Novel insights related to the rise of KPC-producing Enterobacter cloacae complex strains within the nosocomial niche

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.2022.951049

DOI=10.3389/fcimb.2022.951049

ISSN=2235-2988

ABSTRACT=<p>According to the World Health Organization, carbapenem-resistant <italic>Enterobacteriaceae</italic> (CRE) belong to the highest priority group for the development of new antibiotics. Argentina-WHONET data showed that Gram-negative resistance frequencies to imipenem have been increasing since 2010 mostly in two CRE bacteria: <italic>Klebsiella pneumoniae</italic> and <italic>Enterobacter cloacae</italic> Complex (ECC). This scenario is mirrored in our hospital. It is known that <italic>K. pneumoniae</italic> and the ECC coexist in the human body, but little is known about the outcome of these species producing KPC, and colonizing or infecting a patient. We aimed to contribute to the understanding of the rise of the ECC in Argentina, taking as a biological model both a patient colonized with two KPC-producing strains (one <italic>Enterobacter hormaechei</italic> and one <italic>K. pneumoniae</italic>) and <italic>in vitro</italic> competition assays with prevalent KPC-producing ECC (KPC-ECC) versus KPC-producing <italic>K. pneumoniae</italic> (KPC-Kp) high-risk clones from our institution. A KPC-producing <italic>E. hormaechei</italic> and later a KPC-Kp strain that colonized a patient shared an identical novel conjugative IncM1 plasmid harboring <italic>bla</italic><sub>KPC-2</sub>. In addition, a total of 19 KPC-ECC and 58 KPC-Kp strains isolated from nosocomial infections revealed that high-risk clones KPC-ECC ST66 and ST78 as well as KPC-Kp ST11 and ST258 were prevalent and selected for competition assays. The competition assays with KCP-ECC ST45, ST66, and ST78 versus KPC-Kp ST11, ST18, and ST258 strains analyzed here showed no statistically significant difference. These assays evidenced that high-risk clones of KPC-ECC and KPC-Kp can coexist in the same hospital environment including the same patient, which explains from an ecological point of view that both species can exchange and share plasmids. These findings offer hints to explain the worldwide rise of KPC-ECC strains based on the ability of some pandemic clones to compete and occupy a certain niche. Taken together, the presence of the same new plasmid and the fitness results that showed that both strains can coexist within the same patient suggest that horizontal genetic transfer of <italic>bla</italic><sub>KPC-2</sub> within the patient cannot be ruled out. These findings highlight the constant interaction that these two species can keep in the hospital environment, which, in turn, can be related to the spread of KPC.</p>