Comparative Proteomics of Inner Membrane Fraction from Carbapenem-Resistant Acinetobacter baumannii with a Reference Strain

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.

Significances of OMV and Extracellular Vesicle Proteomics

“…Carbapenem resistant A. baumannii has been already studied using outer membrane proteomics between wild type and resistance strain [108,[140][141][142]. Membrane proteomics result also showed that A. baumannii displays a vigorous and adaptable metabolism [143,144].…”

Proteomic Studies of the Effects of Different Stress Conditions on Central Carbon Metabolism in Microorganisms

“…Acinetobacter baumannii has emerged over several decades as a problematic human pathogen, the major cause of healthcare-associated infections including bacteremia, pneumonia, meningitis, urinary tract infection, and wound infection [38,39]. The carbapenems are a class of β-lactam antibiotics most commonly prescribed to treat infection, but A. baumannii has developed resistance leading to significant health [38].…”

“…The carbapenems are a class of β-lactam antibiotics most commonly prescribed to treat infection, but A. baumannii has developed resistance leading to significant health [38]. Proteomic analysis of the inner-membrane fraction of a carbapenem-resistant strain of A. baumannii, using differential in-gel electrophoresis (DIGE) with DeCyder, Progenesis and LC-MS/MS, identified 19 over-expressed and 4 down-regulated proteins in the resistant strain (RS307) compared to the reference (ATCC 19606) [39]. Proteins up-regulated in the resistant strain are associated with β-lactamase, protein synthesis and chaperonins, seven of which have a role in metabolism and energy production.…”

Structural studies on New Delhi Metallo-β-lactamase (NDM-2) suggest old β-lactam, penicillin to be better antibiotic for NDM-2-harbouringAcinetobacter baumanni

“…β-lactams inhibit the membrane synthesis and therefore kill bacteria. In order to escape the action of β-lactams, A. baumannii primarily utilizes production of β-lactamases, enzymes which cleave the β-lactam ring (Garau et al, 2005;Kohlenberg et al, 2009;Peleg et al, 2008;Tiwari, et al, 2012a;Tiwari et al, 2012b;Walsh, Toleman, Poirel, & Nordmann, 2005). Catalytic degradation of β-lactam by β-lactamase involves the formation of transient complex (β-lactamase-β-lactam) which subsequently releases hydrolyzed β-lactam.…”