Enterobacter cloacae Complex: Clinical Impact and Emerging Antibiotic Resistance

Maria Lina Mezzatesta; Floriana Gona; Stefania Stefani


Future Microbiol. 2012;7(7):887-902. 

In This Article

Mechanisms of Pathogenicity

Little is known about the factors impacting the pathogenicity and virulence of Enterobacter spp. As Gram-negative pathogens, they possess endotoxins and thus have all of the pathogenetic properties imparted to an organism by this virulence factor.[1] The possible pathogenetic mechanism is complex and multifactorial, with the involvement of a number of putative virulence factors, whose role in the development of the disease is still not clear. Barnes et al. report that after adhesion to the epithelial cells, in vitroEnterobacter spp. strains produce many potential virulence factors, including enterotoxins, α-hemolysin and thiol-activated pore-forming cytotoxins similar to Shiga-like toxin II, which require treatment with 2-mercaptoethanol.[22] In several Gram-negative bacteria, the type III secretion system (TTSS) has been shown to be an important factor that plays a crucial role in host–pathogen interactions. The TTSS consists of several proteins assembled in a system that delivers virulence factors, usually toxins, directly into the host cells. Hence, the presence of the TTSS can be used as a general indicator of bacterial virulence.[23] In a study by Krzyminska et al., TTSS genes were present in 27% of the E. cloacae isolated from clinical specimens, indicating that these bacteria may destroy phagocytes and epithelial cells, leading to their spread within the host.[24] The results of this study demonstrate that cytotoxic enterotoxins activated by 2-mercaptoethanol and the TTSS may contribute to E. cloacae pathogenesis. In a recent study, it has been demonstrated that the E. cloacae complex strains may induce apoptosis of HEp-2 cells.[25] This process may be a primary strategy of the strains, resulting in tissue destruction, bacterial spreading and, as a consequence, invasive disease or systemic infection. These mechanisms may be considered as contributing factors in disease development. Finally, some studies have found that the biofilm formation on and the colonization of inert surfaces in Enterobacteriaceae are due to a class of proteinaceous extracellular fibers, defined 'curli fimbriae', which mediate binding to a variety of host proteins and also mediate host cell adhesion and invasion.[26,27] Recently, Kim et al. have demonstrated a good correlation between the phenotypic detection of curli fimbriae and the genotypic detection of the curli gene, suggesting the importance of these fimbriae in the formation and morphology of biofilms in E. cloacae.[28]