Molecular biology reports · 2026
Molecular Characterization of vanA and blaTEM Mutant Genes in Enterococcus faecalis: In silico and in vitro investigation of Sitagliptin as a potential Resistance Modulator.
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Alabdali Yasir Adil Jabbar, Munahi Murad G, Dawood Yessar A, Kudhair Bassam K, Al-Hejjaj Murtakab Y, Aziz Zahraa Nafeh
Аннотация
BACKGROUND: E. faecalis is an important opportunistic pathogen increasingly associated with multi-drug resistance infections, particularly through the spreading of resistance genes such as vanA and blaTEM.
METHODS AND RESULTS: In the present work, we examined the frequency of two resistance genes in E. faecalis isolated from clinical specimens in Al-Muthanna, Iraq, and investigated the potential of sitagliptin as a resistance-modulating agent. Among 350 samples, 83 isolates (23.71%) were identified as E. faecalis, and they were significantly implicated in cases of urinary catheter and pyelonephritis (p = 0.045). The resistance profile showed maximum resistance to amoxicillin/clavulanate (95.2%), followed by vancomycin (13.3%) and sitagliptin (2.4%). Molecular analysis confirmed the presence of the vanA and blaTEM resistance genes. Sequence analysis of selected isolates revealed single nucleotide polymorphisms (SNPs) in vanA (G521A and C560T) and in blaTEM (G244A), leading to amino acid substitutions. Gene expression analysis by qRT-PCR showed that vanA expression was up-regulated by vancomycin (1.47-fold), while sitagliptin exposure resulted in altered expression levels (3.66-fold). Likewise, blaTEM expression was down-regulated from 1.95-fold under antibiotic induction to 0.75-fold following sitagliptin treatment. A synergistic effect was observed in checkerboard assays when sitagliptin was combined with amoxicillin. Phylogenetic analysis of 16 S rRNA sequences supported the close genetic relatedness of the local E. faecalis isolates with strains reported from China, Hungary, and Tunisia, suggesting possible international dissemination patterns.
CONCLUSION: In conclusion, sitagliptin demonstrated a modulatory effect on the major resistance genes (vanA and blaTEM) in E. faecalis without clear bactericidal activity, indicating its potential role as a resistance-modifying agent. These findings encourage further investigation of sitagliptin as a possible adjunct therapeutic option against multidrug-resistant enterococcal infections.
METHODS AND RESULTS: In the present work, we examined the frequency of two resistance genes in E. faecalis isolated from clinical specimens in Al-Muthanna, Iraq, and investigated the potential of sitagliptin as a resistance-modulating agent. Among 350 samples, 83 isolates (23.71%) were identified as E. faecalis, and they were significantly implicated in cases of urinary catheter and pyelonephritis (p = 0.045). The resistance profile showed maximum resistance to amoxicillin/clavulanate (95.2%), followed by vancomycin (13.3%) and sitagliptin (2.4%). Molecular analysis confirmed the presence of the vanA and blaTEM resistance genes. Sequence analysis of selected isolates revealed single nucleotide polymorphisms (SNPs) in vanA (G521A and C560T) and in blaTEM (G244A), leading to amino acid substitutions. Gene expression analysis by qRT-PCR showed that vanA expression was up-regulated by vancomycin (1.47-fold), while sitagliptin exposure resulted in altered expression levels (3.66-fold). Likewise, blaTEM expression was down-regulated from 1.95-fold under antibiotic induction to 0.75-fold following sitagliptin treatment. A synergistic effect was observed in checkerboard assays when sitagliptin was combined with amoxicillin. Phylogenetic analysis of 16 S rRNA sequences supported the close genetic relatedness of the local E. faecalis isolates with strains reported from China, Hungary, and Tunisia, suggesting possible international dissemination patterns.
CONCLUSION: In conclusion, sitagliptin demonstrated a modulatory effect on the major resistance genes (vanA and blaTEM) in E. faecalis without clear bactericidal activity, indicating its potential role as a resistance-modifying agent. These findings encourage further investigation of sitagliptin as a possible adjunct therapeutic option against multidrug-resistant enterococcal infections.