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Comparative proteomics of inner membrane fraction from carbapenem-resistant Acinetobacter baumannii with a reference strain.

Tiwari V, Vashistt J, Kapil A, Moganty RR - PLoS ONE (2012)

Bottom Line: Increased resistance of A.baumannii even to the latest generation of β-lactams like carbapenem is an immediate threat to mankind.Further, entry of carbapenem perhaps is limited by controlled production of OmpW and low levels of surface antigen help to evade host defence mechanism in developing resistance in A.baumannii.Present results support a model for the importance of proteins of inner-membrane fraction and their synergistic effect in the mediation of resistance of A.baumannii to carbapenem.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

ABSTRACT
Acinetobacter baumannii has been identified by the Infectious Diseases Society of America as one of the six pathogens that cause majority of hospital infections. Increased resistance of A.baumannii even to the latest generation of β-lactams like carbapenem is an immediate threat to mankind. As inner-membrane fraction plays a significant role in survival of A.baumannii, we investigated the inner-membrane fraction proteome of carbapenem-resistant strain of A.baumannii using Differential In-Gel Electrophoresis (DIGE) followed by DeCyder, Progenesis and LC-MS/MS analysis. We identified 19 over-expressed and 4 down-regulated proteins (fold change>2, p<0.05) in resistant strain as compared to reference strain. Some of the upregulated proteins in resistant strain and their association with carbapenem resistance in A.baumannii are: i) β-lactamases, AmpC and OXA-51: cleave and inactivate carbapenem ii) metabolic enzymes, ATP synthase, malate dehydrogenase and 2-oxoglutarate dehydrogenase: help in increased energy production for the survival and iii) elongation factor Tu and ribosomal proteins: help in the overall protein production. Further, entry of carbapenem perhaps is limited by controlled production of OmpW and low levels of surface antigen help to evade host defence mechanism in developing resistance in A.baumannii. Present results support a model for the importance of proteins of inner-membrane fraction and their synergistic effect in the mediation of resistance of A.baumannii to carbapenem.

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Schematic presentation of upregulated (↑) and downregulated (↓) proteins in the carbapenem-resistant A.baumannii.
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pone-0039451-g002: Schematic presentation of upregulated (↑) and downregulated (↓) proteins in the carbapenem-resistant A.baumannii.

Mentions: Acquired resistance to carbapenem, in A.baumannii is a multifactorial phenomenon in which the bacterium applies a number of intricate and robustic means to evade the antimicrobial effect of antibiotic. Increased production of β-lactamases to cleave the antibiotic is the first step in developing resistance. It appears that A.baumannii employs efficient and robust metabolic mechanisms by increasing the production of metabolic enzymes, as is evident from the present data. It is tempting to speculate that, elevated levels of ribosomal proteins and chaperonin may help in rapid translation and proper folding of metabolic enzymes respectively. In addition, A.baumannii down regulates a number of proteins like surface antigen which assist in evading host defence mechanism. In conclusion, A.baumannii seems to apply a number of ways which work cooperatively and synergistically which help in developing resistance to antibiotic in clinical strain with respect to reference strain. Present finding are schematically summarized in Figure 2.


Comparative proteomics of inner membrane fraction from carbapenem-resistant Acinetobacter baumannii with a reference strain.

Tiwari V, Vashistt J, Kapil A, Moganty RR - PLoS ONE (2012)

Schematic presentation of upregulated (↑) and downregulated (↓) proteins in the carbapenem-resistant A.baumannii.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3383706&req=5

pone-0039451-g002: Schematic presentation of upregulated (↑) and downregulated (↓) proteins in the carbapenem-resistant A.baumannii.
Mentions: Acquired resistance to carbapenem, in A.baumannii is a multifactorial phenomenon in which the bacterium applies a number of intricate and robustic means to evade the antimicrobial effect of antibiotic. Increased production of β-lactamases to cleave the antibiotic is the first step in developing resistance. It appears that A.baumannii employs efficient and robust metabolic mechanisms by increasing the production of metabolic enzymes, as is evident from the present data. It is tempting to speculate that, elevated levels of ribosomal proteins and chaperonin may help in rapid translation and proper folding of metabolic enzymes respectively. In addition, A.baumannii down regulates a number of proteins like surface antigen which assist in evading host defence mechanism. In conclusion, A.baumannii seems to apply a number of ways which work cooperatively and synergistically which help in developing resistance to antibiotic in clinical strain with respect to reference strain. Present finding are schematically summarized in Figure 2.

Bottom Line: Increased resistance of A.baumannii even to the latest generation of β-lactams like carbapenem is an immediate threat to mankind.Further, entry of carbapenem perhaps is limited by controlled production of OmpW and low levels of surface antigen help to evade host defence mechanism in developing resistance in A.baumannii.Present results support a model for the importance of proteins of inner-membrane fraction and their synergistic effect in the mediation of resistance of A.baumannii to carbapenem.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

ABSTRACT
Acinetobacter baumannii has been identified by the Infectious Diseases Society of America as one of the six pathogens that cause majority of hospital infections. Increased resistance of A.baumannii even to the latest generation of β-lactams like carbapenem is an immediate threat to mankind. As inner-membrane fraction plays a significant role in survival of A.baumannii, we investigated the inner-membrane fraction proteome of carbapenem-resistant strain of A.baumannii using Differential In-Gel Electrophoresis (DIGE) followed by DeCyder, Progenesis and LC-MS/MS analysis. We identified 19 over-expressed and 4 down-regulated proteins (fold change>2, p<0.05) in resistant strain as compared to reference strain. Some of the upregulated proteins in resistant strain and their association with carbapenem resistance in A.baumannii are: i) β-lactamases, AmpC and OXA-51: cleave and inactivate carbapenem ii) metabolic enzymes, ATP synthase, malate dehydrogenase and 2-oxoglutarate dehydrogenase: help in increased energy production for the survival and iii) elongation factor Tu and ribosomal proteins: help in the overall protein production. Further, entry of carbapenem perhaps is limited by controlled production of OmpW and low levels of surface antigen help to evade host defence mechanism in developing resistance in A.baumannii. Present results support a model for the importance of proteins of inner-membrane fraction and their synergistic effect in the mediation of resistance of A.baumannii to carbapenem.

Show MeSH
Related in: MedlinePlus