Do biofilm formation and interactions with human cells explain the clinical success of Acinetobacter baumannii?

BACKGROUND: The dramatic increase in antibiotic resistance and the recent manifestation in war trauma patients underscore the threat of Acinetobacter baumannii as a nosocomial pathogen. Despite numerous reports documenting its epidemicity, little is known about the pathogenicity of A. baumannii. The aim of this study was to obtain insight into the factors that might explain the clinical success of A. baumannii. METHODOLOGY/PRINCIPAL FINDINGS: We compared biofilm formation, adherence to and inflammatory cytokine induction by human cells for a large panel of well-described strains of A. baumannii and compared these features to that of other, clinically less relevant Acinetobacter species. Results revealed that biofilm formation and adherence to airway epithelial cells varied widely within the various species, but did not differ among the species. However, airway epithelial cells and cultured human macrophages produced significantly less inflammatory cytokines upon exposure to A. baumannii strains than to strains of A. junii, a species infrequently causing infection. CONCLUSION/SIGNIFICANCE: The induction of a weak inflammatory response may provide a clue to the persistence of A. baumannii in patients.

CsuA/BABCDE-dependent pili are not involved in the adherence of Acinetobacter baumannii ATCC19606(T) to human airway epithelial cells and their inflammatory response.

Acinetobacter baumannii is a nosocomial pathogen responsible for outbreaks of infection worldwide. The factors associated with its ability to colonize/infect human hosts are largely unknown. Adherence to host cells is the first step in colonization/infection, which can be followed by biofilm formation. A. baumannii ATCC19606(T) biofilm formation on abiotic surfaces depends on expression of the CsuA/BABCDE chaperonee-usher pili assembly system. The present study focused on the involvement of CsuA/BABCDE-dependent pili in the interactions between A. baumannii 19606(T) and human bronchial epithelial cells and sheep erythrocytes. Light microscopy analysis revealed that CsuE-mutant #144 adhered to more bronchial epithelial cells than the parental strain. Similar amounts of interleukin (IL)-6 and IL-8 were produced by bronchial epithelial cells in response to these two bacterial strains. Scanning electron microscopy revealed the presence of two types of surface extensions on ATCC19606(T), i.e., short (29 nm; 5-140 nm) pili and long (260 nm; 143-1008 nm) extensions. The latter were not observed on the CsuE-mutant and therefore are likely the previously described CsuA/BABCDE-encoded extensions. We conclude that CsuA/BABCDE-dependent pili are not involved in adherence of A. baumannii ATCC19606(T) to bronchial epithelial cells. The structure of the short pili and their possible role in adherence to human cells requires further investigation.

Adherence of Acinetobacter baumannii strains to human bronchial epithelial cells.

Acinetobacter baumannii is an important nosocomial pathogen, but the mechanisms contributing to its epidemicity and virulence are largely unknown. The organism is able to colonize skin and mucosal surfaces of the human host. Adherence of microorganisms to host cells is an important virulence factor as it is the initial step of the colonization process. In the present study, adherence of A. baumannii to human bronchial epithelial NCI-H(292) cells was examined by light and scanning electron microscopy. Thirty-seven strains were investigated including 18 from outbreaks, 16 not associated with outbreaks, and three for which an epidemic implication was unknown. Eight and 11 isolates belonged to European clone I and II, respectively. Two types of adherence were observed, dispersed adherence of bacteria to the cell, and adherence of clusters of bacteria at localized areas of the cells. Bacteria with dispersed adherence interacted with the epithelial cells through fimbriae, but were also entrapped by protrusions extending from the epithelial cells. Quantitative adherence varied considerably among strains but there was no significant correlation of the outbreak-associated strains with the percentage of infected cells. There was, however, a correlation between the clonal lineage and the percent of infected cells, with clone II being more adherent than clone I (P<0.05). Ten consecutive isolates from one outbreak were investigated to test whether adherence increased during passage among patients, but this appeared not to be the case. This study showed that A. baumannii adheres to human bronchial epithelial cells in vitro and that A. baumannii strains of clone II had a relatively high capacity for adhering to these cells.