| A. baumannii is a strictly aerobic, gram negative, catalase positive, oxidase negative, non-motile, non-fermentative coccobacilli. The genus Acinetobacter has undergone significant taxonomic modification over the last 30 years. Its most important representative, Acinetobacter baumannii, has emerged as one of the most troublesome pathogens for healthcare institutions globally (Peleg et al., 2008). It has a remarkable ability to acquire resistant determinants, threatening the antibiotic resources we comprise today. By such, A. baumannii has proven to be a major cause of healthcare-associated infections worldwide including bacteremia, ventilator-associated pneumonia, urinary tract infection, meningitis and wound infection, particularly in patients admitted to intensive care units (Perez et al., 2007). Carbapenem antibiotics (imipenem and meropenem) have been primarily used to treat A. baumannii infections. However, carbapenem resistant A. baumannii has emerged in patients worldwide and has proved a challenge to treatment of the infections.;Glutathione is a tripeptide (L-gamma-glutamyl-L-cysteinyl-glycine) thiol compound existing in many bacteria, and it maintains a proper cellular redox state thus protecting cells against toxic substances such as reactive oxygen species. Polyamines (spermine and spermidine) are low molecular weight aliphatic polycations ubiquitously present in all living cells, and they modulate many cellular functions. It has been previously reported that exogenous polyamines significantly enhanced beta-lactam susceptibility of beta-lactam-associated multidrug resistant A. baumannii. In this study, three genes differentially associated with the polyamine effect on beta-lactam susceptibility were identified by transposon mutagenesis of A. baumannii ATCC 19606. All three genes encoded components of membrane transport systems. Inactivation of one of the genes, encoding a putative glutathione transport ATP-binding protein, increased the accumulation of intracellular glutathione (∼150 to ∼200 %), which significantly decreased the polyamine effect on beta-lactam susceptibility in A. baumannii ATCC 19606. When the cells were grown with polyamines, the levels of intracellular glutathione of A. baumannii ATCC 19606 significantly decreased from ∼0.5 to ∼0.2 nmol while the levels of extracellular glutathione were correspondingly increased. However, the levels of total glutathione (intracellular and extracellular) remained unchanged when the cells were grown with or without polyamines. Overall, these results suggest that exogenous polyamines induce the glutathione export resulting in decreased-levels of intracellular glutathione, which may produce an improper cellular redox state that is associated with the polyamine-mediated beta-lactam susceptibility of A. baumannii. This finding may provide a clue to develop a new antimicrobial agent and/or novel strategies to treat multidrug resistant A. baumannii.. |
