Abstract
Multidrug resistant microorganisms are forecast to become the single biggest challenge to medical care in the 21st century. Over the last decades, members of the genus Acinetobacter have emerged as bacterial opportunistic pathogens, in particular as challenging nosocomial pathogens because of the rapid evolution of antimicrobial resistances. Although we lack fundamental biological insight into virulence mechanisms, an increasing number of researchers are working to identify virulence factors and to study antibiotic resistance. Here, we review current knowledge regarding the regulation of virulence genes and antibiotic resistance in Acinetobacter baumannii. A survey of the two-component systems AdeRS, BaeSR, GacSA and PmrAB explains how each contributes to antibiotic resistance and virulence gene expression, while BfmRS regulates cell envelope structures important for pathogen persistence. A. baumannii uses the transcription factors Fur and Zur to sense iron or zinc depletion and upregulate genes for metal scavenging as a critical survival tool in an animal host. Quorum sensing, nucleoid-associated proteins, and non-classical transcription factors such as AtfA and small regulatory RNAs are discussed in the context of virulence and antibiotic resistance.
Highlights
Bacterial infections are a leading cause of death worldwide, and the fading age of antibiotics increases risks associated with basic healthcare and surgeries
We provide an overview of current knowledge of the protein and RNA transcription factors that control virulence gene expression and antibiotic resistance in A. baumannii, followed by a brief discussion of research horizons that promise important insights into A. baumannii virulence
In the bacterial pathogen A. baumannii, an increasing number of virulence genes have been identified over the last few years, their gene regulation remains largely unknown
Summary
Bacterial infections are a leading cause of death worldwide, and the fading age of antibiotics increases risks associated with basic healthcare and surgeries. Carbapenem-resistant A. baumannii (CRAB) strains in particular have emerged as one of the most concerning antibiotic-resistant pathogens [16]. Over 50% of A. baumannii isolates from intensive care units are carbapenem-resistant, and therapy of CRAB infections is estimated to cost global healthcare systems in excess of 742 million US Dollars annually [17]. Despite the growing clinical importance of pathogenic strains of A. baumannii, the scientific community has only begun to understand the fundamentals of A. baumannii infection biology. To combat antibiotic resistance and develop knowledge-based interventions, detailed understanding of the resistance mechanisms and the regulation of genes conferring drug resistance are required. We provide an overview of current knowledge of the protein and RNA transcription factors that control virulence gene expression and antibiotic resistance in A. baumannii, followed by a brief discussion of research horizons that promise important insights into A. baumannii virulence
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