INTRODUCTION
Carbapenem-resistant Enterobacteriaceae have become a major threat to global health, with Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli (E. coli) receiving critical priority status from the World Health Organization. These pathogens are particularly concerning due to their resistance to multiple antibiotics and their potential to cause severe infections in healthcare settings. The emergence of blaKPC genes in E. coli, though less common than in K. pneumoniae, represents a growing public health risk, especially with limited therapeutic options available. In this context, a retrospective genomic study was carried out at a Brazilian teaching hospital to better understand the mechanisms underlying antimicrobial resistance, virulence, and evolutionary dynamics of KPC-producing E. coli. The findings not only highlight the genetic diversity among the isolates but also provide insight into resistance trends that may inform infection control strategies and clinical management protocols.
MOLECULAR CHARACTERIZATION OF blaKPC-2
All 40 E. coli isolates analyzed in the study were confirmed to carry the blaKPC-2 gene, which encodes for the carbapenemase enzyme responsible for hydrolyzing carbapenem antibiotics. The blaKPC-2 gene was found to be mobilized by the transposable element Tn4401, emphasizing the gene's ability to disseminate across bacterial populations through horizontal gene transfer. This mechanism is particularly troubling in clinical environments, where high antibiotic pressure can select for these resistant strains. The identification of Tn4401 as a key vector of blaKPC-2 provides valuable molecular insight that could inform surveillance and containment strategies.
ANTIMICROBIAL SUSCEPTIBILITY PATTERNS
Despite the resistance to meropenem, several antibiotics maintained efficacy against the KPC-producing E. coli isolates. Notably, amikacin, tigecycline, colistin, polymyxin B, and fosfomycin showed promising activity. These results offer some hope for treatment, though caution must be exercised due to the potential for rapid resistance development. The susceptibility patterns underscore the importance of routine antimicrobial testing in clinical isolates and suggest that combination therapies or last-resort antibiotics may still be viable in certain scenarios. However, the narrow spectrum of effective drugs demands judicious use and the development of novel therapeutic agents.
GENOMIC DIVERSITY AND SEQUENCE TYPING
The whole-genome sequencing and MLST (multi-locus sequence typing) revealed significant genetic diversity among the 40 isolates, with 20 distinct sequence types (STs) identified. ST131 was the most prevalent, a lineage widely recognized for its global dissemination and association with multidrug resistance. The grouping of genomes by ST indicates clonal spread within the hospital setting, although the diversity also points to multiple introduction events. This genotypic profiling is critical in understanding the transmission dynamics of KPC-producing E. coli and tailoring interventions to prevent further spread within healthcare environments.
VIRULENCE FACTORS AND PATHOGENICITY
In addition to antimicrobial resistance genes, the sequenced isolates harbored a variety of virulence-associated genes that enhance their pathogenic potential. These included genes related to adhesion, iron acquisition, and immune evasion, commonly found in extraintestinal pathogenic E. coli (ExPEC). The co-occurrence of virulence and resistance traits raises significant concerns for public health, as it increases the likelihood of severe, hard-to-treat infections. The predominance of strains from pathogenic phylogroups reinforces the need for vigilant monitoring and infection control practices.
CLINICAL IMPLICATIONS AND PUBLIC HEALTH IMPACT
Although KPC-producing E. coli remains relatively rare compared to other carbapenemase producers, its presence in clinical settings signals a troubling trend. The combination of high virulence and limited treatment options poses a serious threat to vulnerable patient populations. Understanding the genomic context of these organisms is essential for developing rapid diagnostic tools, optimizing therapeutic strategies, and implementing effective infection prevention measures. The study underscores the urgent need for global surveillance systems and sustained research efforts to mitigate the impact of these formidable pathogens.
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