Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

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The number of studies about A. baumannii is increasing dramatically because of its increasing clinical importance. Use of animal models has produced important data regarding virulence factors that contribute to A. baumannii pathogenesis. Notably, some studies on metal acquisition and protein secretion systems are interesting. Besides iron acquisition systems such as acinetobactin, the discovery of zinc and manganese acquisition systems in A. baumannii broadens our understanding of A. baumannii pathogenesis. Recent interest about A. baumannii is mostly due to its seemingly endless capacity to acquire antibiotic resistance. A. baumannii has almost all bacterial resistance mechanisms. All class -lactamases have been detected in A. baumannii and the frequency of carbapenem-resistant A. baumannii isolates is very high. Furthermore, almost all A. baumannii contain aminoglycoside-modifying enzymes and many efflux pumps responsible for resistance to various clinically important antibiotics have been identified in A. baumannii. Due to these abilities, available antibiotics to treat A. baumannii infections are significantly limited. Colistin is used as the antibiotic treatment of last resort, due to its relatively low resistance rate. However, emergence of colistin-resistant A. baumannii strains has increased worldwide with increasing use of colistin. Notably, some more recent studies have proposed that another polymyxin antibiotic, polymyxin B, is a potential therapeutic alternative to colistin. Various trials to identify a novel alternative to carbapenem or colistin have been performed. Among them, engineered endolysins (artilysins) are particularly interesting, despite evident defects. A lytic enzyme degrading peptidoglycan of bacteria is a promising novel class of antimicrobial agents due to its unique mode of action. Similar to -lactam antibiotics that are one of the most successful antibiotics, inhibition of peptidoglycan synthesis is a promising target of antimicrobial agents. Because lytic enzymes directly degrade peptidoglycans, but not proteins, the possibility of the emergence of a resistance mechanism is relatively low.

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