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Structural Variabilities in β-Lactamase (blaA) of Different Biovars of Yersinia enterocolitica: Implications for β-Lactam Antibiotic and β-Lactamase Inhibitor Susceptibilities.

Singhal N, Srivastava A, Kumar M, Virdi JS - PLoS ONE (2015)

Bottom Line: Our findings indicated that neither variations in the promoter regions, nor the secondary structures of mRNA contributed to higher/lower expression of blaA in different biovars.Analysis of H-bonding residues of blaA variants with amoxicillin and clavulanic acid revealed that if amino acid residues of a β-lactamase interacting with amoxicillin and the clavulanic acid were similar, clavulanic acid was effective in engaging the enzyme, accounting for a significant reduction in MIC of amoxicillin-clavulanate.This finding might aid in designing better β-lactamase inhibitors with improved efficiencies in future.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Delhi South Campus, Benito Juarez Road, New Delhi, India.

ABSTRACT
Yersiniosis caused by Yersinia enterocolitica has been reported from all continents. The bacterial species is divided into more than fifty serovars and six biovars viz. 1A, 1B, 2, 3, 4 and 5 which differ in geographical distribution, ecological niches and pathogenicity. Most Y.enterocolitica strains harbor chromosomal genes for two β-lactamases, blaA an Ambler class A penicillinase and blaB an Ambler class C inducible cephalosporinase. In the present study, susceptibility to b-lactam antibiotics and β-lactamase inhibitor was studied for Y. enterocolitica strains of biovars 1A, 1B, 2 and 4. We observed that β-lactamases were expressed differentially among strains of different biovars. To understand the molecular mechanisms underlying such differential expression, the sequences of genes and promoters of blaA were compared. Also, the variants of blaA present in different biovars were modeled and docked with amoxicillin and clavulanic acid. The mRNA secondary structures of blaA variants were also predicted in-silico. Our findings indicated that neither variations in the promoter regions, nor the secondary structures of mRNA contributed to higher/lower expression of blaA in different biovars. Analysis of H-bonding residues of blaA variants with amoxicillin and clavulanic acid revealed that if amino acid residues of a β-lactamase interacting with amoxicillin and the clavulanic acid were similar, clavulanic acid was effective in engaging the enzyme, accounting for a significant reduction in MIC of amoxicillin-clavulanate. This finding might aid in designing better β-lactamase inhibitors with improved efficiencies in future.

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Related in: MedlinePlus

The mRNA secondary structures of blaAx (A), blaAy (B) and blaAz (C)predicted by mfold based on complete coding sequences of different blaAvariants of Y.enterocolitica.
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pone.0123564.g003: The mRNA secondary structures of blaAx (A), blaAy (B) and blaAz (C)predicted by mfold based on complete coding sequences of different blaAvariants of Y.enterocolitica.

Mentions: Apart from variations in the amino acids, other confounding factors like secondarystructure of mRNA, and/or mutations in the promoters of blaA genesmight also influence antibiotic/inhibitor susceptibility of blaA types. Thereforethe secondary structures of mRNA and promoter sequences of blaA types were alsoinvestigated. The mRNA secondary structure directly affects the rate of genetranslation, and thus the enzyme activity. The mfold webserver predicted a similarfree energy change (ΔG values) and similar mRNA secondary structure for thethree blaA types (Fig 3). Thisimplied that the mRNA secondary structure was not responsible for the observedincrease in MIC of AMX and/or AMC inY.enterocolitica biovar 1A. However,introduction of mutations that would change the secondary structure of the mRNAmolecule are required further to validate this finding.


Structural Variabilities in β-Lactamase (blaA) of Different Biovars of Yersinia enterocolitica: Implications for β-Lactam Antibiotic and β-Lactamase Inhibitor Susceptibilities.

Singhal N, Srivastava A, Kumar M, Virdi JS - PLoS ONE (2015)

The mRNA secondary structures of blaAx (A), blaAy (B) and blaAz (C)predicted by mfold based on complete coding sequences of different blaAvariants of Y.enterocolitica.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414059&req=5

pone.0123564.g003: The mRNA secondary structures of blaAx (A), blaAy (B) and blaAz (C)predicted by mfold based on complete coding sequences of different blaAvariants of Y.enterocolitica.
Mentions: Apart from variations in the amino acids, other confounding factors like secondarystructure of mRNA, and/or mutations in the promoters of blaA genesmight also influence antibiotic/inhibitor susceptibility of blaA types. Thereforethe secondary structures of mRNA and promoter sequences of blaA types were alsoinvestigated. The mRNA secondary structure directly affects the rate of genetranslation, and thus the enzyme activity. The mfold webserver predicted a similarfree energy change (ΔG values) and similar mRNA secondary structure for thethree blaA types (Fig 3). Thisimplied that the mRNA secondary structure was not responsible for the observedincrease in MIC of AMX and/or AMC inY.enterocolitica biovar 1A. However,introduction of mutations that would change the secondary structure of the mRNAmolecule are required further to validate this finding.

Bottom Line: Our findings indicated that neither variations in the promoter regions, nor the secondary structures of mRNA contributed to higher/lower expression of blaA in different biovars.Analysis of H-bonding residues of blaA variants with amoxicillin and clavulanic acid revealed that if amino acid residues of a β-lactamase interacting with amoxicillin and the clavulanic acid were similar, clavulanic acid was effective in engaging the enzyme, accounting for a significant reduction in MIC of amoxicillin-clavulanate.This finding might aid in designing better β-lactamase inhibitors with improved efficiencies in future.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Delhi South Campus, Benito Juarez Road, New Delhi, India.

ABSTRACT
Yersiniosis caused by Yersinia enterocolitica has been reported from all continents. The bacterial species is divided into more than fifty serovars and six biovars viz. 1A, 1B, 2, 3, 4 and 5 which differ in geographical distribution, ecological niches and pathogenicity. Most Y.enterocolitica strains harbor chromosomal genes for two β-lactamases, blaA an Ambler class A penicillinase and blaB an Ambler class C inducible cephalosporinase. In the present study, susceptibility to b-lactam antibiotics and β-lactamase inhibitor was studied for Y. enterocolitica strains of biovars 1A, 1B, 2 and 4. We observed that β-lactamases were expressed differentially among strains of different biovars. To understand the molecular mechanisms underlying such differential expression, the sequences of genes and promoters of blaA were compared. Also, the variants of blaA present in different biovars were modeled and docked with amoxicillin and clavulanic acid. The mRNA secondary structures of blaA variants were also predicted in-silico. Our findings indicated that neither variations in the promoter regions, nor the secondary structures of mRNA contributed to higher/lower expression of blaA in different biovars. Analysis of H-bonding residues of blaA variants with amoxicillin and clavulanic acid revealed that if amino acid residues of a β-lactamase interacting with amoxicillin and the clavulanic acid were similar, clavulanic acid was effective in engaging the enzyme, accounting for a significant reduction in MIC of amoxicillin-clavulanate. This finding might aid in designing better β-lactamase inhibitors with improved efficiencies in future.

Show MeSH
Related in: MedlinePlus