Can Targeting Iron Help in Combating Chronic Pseudomonas Infection? A Systematic Review

Abstract

Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by Pseudomonas aeruginosa (P. aeruginosa). Eradication of these infections has become a challenge as P. aeruginosa has developed resistance to multiple antibiotics. In several studies, iron has been shown to play an integral role in biofilm formation, which is the predominant resistance mechanism used by P. aeruginosa to combat antibiotics. The increased iron content in cystic fibrosis patients' sputum samples explains their increased susceptibility to Pseudomonas infections. Hence in this review article, we have used the research data available on therapeutic agents that target iron as an adjuvant treatment for chronic Pseudomonas infection. We systematically screened three databases using focused words and Medical Subject Headings (MeSH) terms for relevant articles. Further, we applied the inclusion and exclusion criteria and performed a thorough quality appraisal. Thirty shortlisted relevant studies were meticulously reviewed. In our opinion, novel therapeutic approaches targeting iron such as iron chelators, gallium, and cefiderocol have potent anti-biofilm properties. Future studies and clinical trials using these approaches in the management of chronic Pseudomonas infection might help in decreasing morbidity and mortality in patients with cystic fibrosis. Exploring these approaches might also help to combat other resistant organisms whose survival is dependent on iron.

Single nucleotide variants in Pseudomonas aeruginosa populations from sputum correlate with baseline lung function and predict disease progression in individuals with cystic fibrosis

“…Updated AmpliSeq panels or whole-genome sequencing, along with targeted experimental studies, could be used to test the hypothesis that variation in these genes plays a role in disease progression. Multiple studies have shown competition for iron to be key for the survival and virulence of many of the pathogens that reside in the CF lung, including Pa [59, 60]. We also found that SNVs predictive of lung function decline are enriched in genes involved in stress/metabolism.…”

Cefiderocol to manage chronic, multi-drug-resistant Burkholderia cepacia complex infection in a patient with cystic fibrosis: a case report

“…The management of pulmonary infections, and Bcc infection specifically, requires that clinicians assess each person individually, taking into account symptomatic changes, previous clinical responses and their own experiences [3]. Evidence from the literature, which to date is largely founded on in vitro studies or case reports, supports that cefiderocol is an antibiotic that appears to expand the treatment options for CF patients colonized with MDR Gram-negative bacilli [15][16][17][18][19][20].…”

Single nucleotide variants in Pseudomonas aeruginosa populations from sputum correlate with baseline lung function and predict disease progression in individuals with cystic fibrosis

“…Updated AmpliSeq panels or whole-genome sequencing, along with targeted experimental studies, could be used to test the hypothesis that variation in these genes plays a role in disease progression. Multiple studies have shown competition for iron to be key for the survival and virulence of many of the pathogens that reside in the CF lung, including Pa (Bouvier 2016, Firoz, Haris et al 2021). We also found that SNVs predictive of lung function decline are enriched in genes involved in stress/metabolism.…”