br Conclusion br Acknowledgments br Introduction A

Conclusion
Acknowledgments
Introduction A. baumannii is a leading cause of nosocomial bacteremia, severe pneumonia, meningitis, infections of the urinary tract, bloodstream and other parts of the body. The emergence of sharply increasing rate of Multidrug-resistant A. Baumannii (MDRAB) infection among critically ill, hospitalized patients, and subsequent epidemics, is a pressing problem in many hospitals worldwide. One of the reasons is that the bacteria can live up to 5months on undisturbed surfaces depending on tolerance to desiccation, and multidrug resistance. Emergence of MDRAB is due to antibiotic-selective pressure and its treatment has been challenging because of extensive antimicrobial drug resistance. Colistin, often used as one of the last-resort Q-VD(OMe)-OPh for multidrug-resistant Pseudomonas aeruginosa, and Acinetobacter spp., is also effective against new Delhi metallo-β-Lactamase multidrug-resistant Enterobacteriaceae. Colistin, produced by certain strains of Bacillus polymyxa var. colistinus, is a polycationic antibiotic of cyclic polypeptides. Colistin interacts with the bacterial outer membrane by displacing bacterial counter cationic in the lipopolysaccharide and solubilizes the membrane in an aqueous environment. Resistance to colistin is not common, but A. baumannii resistance to colistin has been reported before. Recently, there has been an alarming trend with regards to the emergence of colistin-resistant A. baumannii. The pressing goal of this research, therefore, was to study the genetic characteristics and mechanisms of colistin-resistance in MDR A. baumannii. In several gram-negative bacteria, such as Salmonella enterica and Pseudomonas aeruginosa, the mechanisms of colistin resistance include modifications, absence or complete loss of the lipid A of the outer membrane lipopolysaccharide (LPS), which reduce or abolish initial charge-based interaction with colistin. The PmrA/B system is involved in downregulating the LPS core and lipid A regions, and the lpxA/D/C gene mutations are involved in modifying biosynthesis of lipid A in resistant strains. However, the mechanism of colistin resistance in A. baumannii is currently unclear. Lipopolysaccharides (LPS) form the major component of the outer membrane of gram-negative bacteria, contributing greatly to the structural integrity of the bacteria, and providing an effective hydrophobic barrier to a variety of aggressive conditions, including antibiotics. Lipid A is a crucially important component of LPS, engaging in phosphorylated glucosamine disaccharide decorated with multiple fatty acids. These hydrophobic fatty acid chains anchor the LPS into the bacterial membrane. Expression of pmrA/B gene -regulating system is involved in the lipid A biosynthesis amount. The lpxA, lpxC and lpxD genes determine mainly the first three steps in the pathway of lipid A biosynthesis, and the hydrophobic anchor of lipopolysaccharide (LPS). Our recent work indicated that pmrA and pmrB gene overexpression could down-regulate lipid A biosynthesis resulting in the increase of colistin resistance. Mutations of lpxA, lpxC and lpxD, may play a role in the development of colistin resistance in clinical A. Baumannii isolates. These strains have lost their capability of producing lipid A and therefore LPS. Understanding the mechanism of resistance to colistin may guide the development of new therapies that are imperative for MDR A. baumannii treatment. It is, therefore, very important to discover alternative therapies coupled with the development of a clinical antibiotic resistant monitor testing and the prevention of transmission of MDR A. baumannii infections.
Materials and methods
Results
Discussion In our present collection of colistin-resistant isolates of A. baumannii, we also found 3 colistin-resistant-dependent strains (Col-D). Colistin-resistance as well as colistin-dependence have been documented previously in other species. E-test showed that MICs of colistin for these 3 Col-D strains were over 256µg/ml and MICs of Colistin for other Col-R strains ranged from 8 to over 256µg/ml respectively.