Pseudomonas aeruginosa and Burkholderia cenocepacia are predominant opportunistic pathogens in cystic fibrosis (CF) patients. In healthy humans the lower respiratory tract as well as all mucosa, contains a very low free iron concentration (10⁻¹⁸ M), while in CF patients' sputum iron concentration is very high, showing a median value of 63×10⁻⁶ M. Accumulation of catalytic reactive iron heavily contributes to subsequent clinical complications in the lung disorders by the production of reactive oxygen species and increases bacterial growth and virulence. The data reported in this study indicate that low iron concentration (Fe³⁺1 μM) induced free-living forms and motility both in P. aeruginosa and B. cenocepacia, while high iron concentrations (Fe³⁺ 10 and 100 μM) stimulated aggregation and biofilm formation already in the fluid phases, so demonstrating that aggregation and biofilm formation are positively iron-modulated in these bacteria. Moreover, the different morphological forms (free-living, aggregates and biofilm) showed different capabilities of adhering and invading the bronchial cell line A549. P. aeruginosa PAO1 aggregates, and mostly biofilm, exerted the highest adhesion efficiency, while B. cenocepacia PV1 aggregates or biofilm the lowest. A significant reduction in invasion efficiency by P. aeruginosa biofilm and a significant increase in cell internalization by B. cenocepacia biofilm has been reported. Therefore, the iron availability is an important signal to which P. aeruginosa and B. cenocepacia counteract by leaving the motile free-living forms and entering into a new lifestyle, i.e. biofilm. These data could contribute to explain that the iron-overload of the sputum of CF patients, inducing nonmotile forms, aggregates and biofilm, may facilitate penetration of host epithelial barriers contributing to the establishment of infection, colonization, persistence and systemic spread of these opportunistic pathogens.

Urinary tract infections (UTIs) are among the most common infections worldwide. Uropathogenic Escherichia coli (UPECs) are the main causative agent of UTIs. UPECs initially colonize the human host adhering to the bladder epithelium. Adhesion is followed by the bacterial invasion of urothelial epithelial cells where they can replicate to form compact aggregates of intracellular bacteria with biofilm-like properties. UPEC strains may persist within epithelial urothelial cells, thus acting as quiescent intracellular bacterial reservoirs (QIRs). It has been proposed that host cell invasion may facilitate both the establishment and persistence of UPECs within the human urinary tract. UPEC strains express a variety of virulence factors including fimbrial and afimbrial adhesins, invasins, iron-acquisition systems, and toxins, which cooperate to the establishment of long lasting infections. An increasing resistance rate relative to the antibiotics recommended by current guidelines for the treatment of UTIs and an increasing number of multidrug resistant UPEC isolates were observed. In order to ameliorate the cure rate and improve the outcomes of patients, appropriate therapy founded on new strategies, as alternative to antibiotics, needs to be explored. Here, we take a snapshot of the current knowledge of coordinated efforts to develop innovative anti-infective strategies to control the diffusion of UPECs.