Iron metabolism in bacterial cells: from physiological significance to a new class of antimicrobial agents

Abstract

Infectious complications in the respiratory tract caused by microorganisms from the Burkholderia cepacia complex are the main cause of death among patients with cystic fibrosis. Natural and acquired resistance mechanisms allow Burkholderia cepacia complex pathogens to adapt to the conditions of regular antibiotic therapy, which necessitates the use of antibacterial drugs with an alternative mechanism of action. Studies on the importance of iron as an essential factor in the metabolism of bacteria and methods of its acquisition from the environment contributed to the development of a new antibiotic from a number of cephalosporins – cefiderocol. In the structure of cefiderocol, a fragment is formed that imitates siderophores – chelating molecules that ensure the transport of iron ions into the internal environment of the microorganism. A unique mechanism, described in the scientific literature as a “Trojan horse”, allows antibiotic molecules conjugated with siderophores to effectively penetrate into the bacterial cell, exerting a bactericidal effect. Thus, cefiderocol can be used to treat infectious complications in the lungs of patients with cystic fibrosis caused by bacteria from the Burkholderia cepacia complex, including multidrug-resistant strains. In addition, the spectrum of activity of cefiderocol allows the use of this antibiotic in the treatment of infections caused by nosocomial gram-negative bacteria such as Enterobacterales, Acinetobacter, Pseudomonas and Stenotrophomonas.