Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance

Abstract

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. First described in 1960, this group member has proven to be more complex as a result of the exponential evolution of phenotypic and genotypic methods. Today, 22 species belong to the Enterobacter genus. These species are described in the environment and have been reported as opportunistic pathogens in plants, animals, and humans. The pathogenicity/virulence of this bacterium remains rather unclear due to the limited amount of work performed to date in this field. In contrast, its resistance against antibacterial agents has been extensively studied. In the face of antibiotic treatment, it is able to manage different mechanisms of resistance via various local and global regulator genes and the modulation of the expression of different proteins, including enzymes (β-lactamases, etc.) or membrane transporters, such as porins and efflux pumps. During various hospital outbreaks, the Enterobacter aerogenes and E. cloacae complex exhibited a multidrug-resistant phenotype, which has stimulated questions about the role of cascade regulation in the emergence of these well-adapted clones.

Keywords: Enterobacter spp.; clinical aspects; diagnosis; efflux; epidemiology; impermeability; multidrug resistance; pathogenicity; β-lactamases.

FIG 1

Schematic representation of the regulation pathways that control the expression of porins and efflux pumps and their interconnection in Enterobacter spp. The multiple regulation cascades that can modulate the outer membrane permeability (porins and LPS) and the expression of major efflux pumps (AcrAB and OqxAB) are summarized. Blue arrows represent transcriptional activation/repression of different genes, such as acrR and ompX, by the global regulators (e.g., Mar, Ram, and Sox). Red arrows symbolize the external stress signals that can activate/repress some gene expression. Black arrows indicate the negative regulation of gene expression (thin line directly on promoter/operator region). Yellow squares illustrate some unknown regulation that can modulate gene expression on promoter/operator regions (represented by dashed boxes) of key loci. Dashed lines represent hypothesized regulation.