Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals, Food and the Environment

Abstract

The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem resistance (CR) in Enterobacteriaceae caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. Carbapenem-resistant Enterobacteriaceae (CRE) isolates have been reported not only in nosocomial and community-acquired pathogens but also in food-producing animals, companion animals, and the environment. The reported carbapenemases in Enterobacteriaceae from different sources belong to the Ambler class A (bla_KPC), class B (bla_IMP, bla_VIM, bla_NDM), and class D (bla_OXA-48) β-lactamases. The carbapenem encoding genes are often located on plasmids or associated with various mobile genetic elements (MGEs) like transposons and integrons, which contribute significantly to their spread. These genes are most of the time associated with other antimicrobial resistance genes such as other β-lactamases, as well as aminoglycosides and fluoroquinolones resistance genes leading to multidrug resistance phenotypes. Control strategies to prevent infections due to CRE and their dissemination in human, animal and food have become necessary. Several factors involved in the emergence of CRE have been described. This review mainly focuses on the molecular epidemiology of carbapenemases in members of Enterobacteriaceae family from humans, animals, food and the environment.

Keywords: Enterobacteriales; animal; carbapenemases; environment; food; human.

Figure 1

Chemical Structures of various carbapenems: (a) Imipenem; (b) Meropenem; (c) Ertapenem; (d) Doripenem; (e) Biapenem; (f) Faropenem; (g) Panipenem, obtained from the National Center for Biotechnology Information (NCBI) PubChem database.

Figure 2

Mechanism of action of β-lactam antibiotics compared to that of vancomycin on the bacterial cell wall. Beta-lactams bind to and inhibit enzymes (PBPs: transpeptidases) which catalyse the final crosslinking (transpeptidation) of the nascent peptidoglycan layer which disrupt cell wall synthesis. Updated from Neu and Gootz, 1996, Ch. 11. Antimicrobial Chemotherapy in Medical Microbiology. 4th edition. Baron, editor. Galveston (TX): University of Texas Medical Branch at Galveston, USA.

Figure 3

Major mechanisms associated with carbapenem-resistance in Gram-negative bacteria. (I) Production of carbapenemases enzyme from gene located on chromosome or plasmid that hydrolyze carbapenem antibiotics shown in golden rectangles. (II) Decreased permeability of the outer membrane due to structural mutations in porins (modified porins shown as red circle). (III) Drug efflux pumps. The blue and grey rectangles represent the chromosomal loci that encode various membrane associated proteins. Abbreviations: LPS, lipopolysaccharides; OM, outer membrane; IM, inner membrane; PG, peptidoglycan.