Gentamicin modulates pgaA and pgaB expression in Klebsiella pneumoniae: Insights into biofilm-associated adaptation
Year: 2025
Type: article
Abstract: Background: Klebsiella pneumoniae is a clinically significant Gram-negative pathogen whose persistence and virulence are strongly linked to biofilm formation. Biofilms protect bacterial cells from host immune responses and antibiotic action, promoting chronic and recurrent infections. The poly-β-1,6-N-acetyl-D-glucosamine (PNAG) biosynthetic cluster (pgaABCD) is essential for biofilm formation, where pgaA encodes an outer membrane protein responsible for PNAG export, and pgaB encodes a deacetylase that stabilizes the biofilm matrix. This study aimed to assess the regulatory effect of gentamicin on pgaA and pgaB expression in clinical K. pneumoniae isolates to elucidate antibiotic–biofilm interactions. Methods: Fifty-six clinical isolates were identified using VITEK 2 and biochemical assays. Antimicrobial susceptibility was determined by the disk diffusion method, and gentamicin minimum inhibitory concentrations were assessed by broth microdilution. Biofilm formation was quantified using the crystal violet assay, while pgaA and pgaB expression levels were measured by quantitative real-time PCR using the 2^−ΔΔCt method with 16S rRNA as a reference gene. Results: High resistance was observed across antibiotic classes, with carbapenems showing the highest resistance (≥86%). Among isolates, 78.57% were multidrug-resistant (MDR), 17.86% extensively drug-resistant (XDR), and 3.57% pandrug-resistant (PDR). Gentamicin exposure markedly influenced biofilm formation, with pgaA expression increased from 17.3-fold to 264.6-fold, while pgaB decreased from 33.5-fold to 11.2-fold post-treatment. Gentamicin exerts a selective regulatory effect on biofilm-associated genes, promoting pgaA-mediated PNAG export while downregulating pgaB. Conclusion: This adaptive mechanism reinforces biofilm integrity under antibiotic stress, highlighting pgaA as a potential marker for biofilm-mediated resistance and a target for novel anti-biofilm therapies against MDR K. pneumoniae.
Authors: Marwah Jamal Khalaf, Haneen Ali Ibrahim, Huda Abbas Abd, Maryam Qasim Mohammed, Asmaa Samir Mohsin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4416850127
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