The Citrobacter freundii Complex as an Emerging Pathogen: Genomic Plasticity, Virulence, and Antimicrobial Resistance

The Citrobacter freundii (C. freundii) complex represents an increasingly significant group of opportunistic pathogens within healthcare settings. This bacterial complex demonstrates remarkable genomic plasticity, characterized by extensive horizontal gene transfer capabilities that facilitate rapid acquisition of resistance determinants and virulence factors. Although originally considered environmental organisms with limited pathogenic potential, members of the C. freundii complex have emerged as important nosocomial pathogens responsible for urinary tract infections, bacteremia, wound infections, and neonatal meningitis. Importantly, their clinical significance lies less in unique disease manifestations and more in the moderate risk of resistance emergence during therapy with third-generation cephalosporins, driven by inducible chromosomal AmpC β-lactamase production. Beyond this intrinsic mechanism, the genomic adaptability of the C. freundii complex also enables acquisition of additional resistance determinants, including extended-spectrum β-lactamases (ESBLs) and carbapenemases, further limiting therapeutic options and complicating clinical management. Understanding the molecular mechanisms underlying genomic plasticity, virulence expression, and resistance development in the C. freundii complex is crucial for developing effective diagnostic strategies, infection control measures, and novel therapeutic approaches. This pathogen exemplifies the challenge of emerging multidrug-resistant bacteria in contemporary healthcare and underscores the need for continued surveillance and research. This narrative review provides current insights into the taxonomy, genomic plasticity, virulence, and mechanisms of antibiotic resistance.