The unusual glycine-rich C terminus of the Acinetobacter baumannii RNA chaperone Hfq plays an important role in bacterial physiology

• Published in: The Journal of biological chemistry Vol. 293; no. 35; pp. 13377 - 13388
• Main Authors: Sharma, Atin, Dubey, Vineet, Sharma, Rajnikant, Devnath, Kuldip, Gupta, Vivek Kumar, Akhter, Jawed, Bhando, Timsy, Verma, Aparna, Ambatipudi, Kiran, Sarkar, Mihir, Pathania, Ranjana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.08.2018; American Society for Biochemistry and Molecular Biology
• Subjects: AbsR25; Acinetobacter baumannii - chemistry; Acinetobacter baumannii - growth & development; Acinetobacter baumannii - physiology; Acinetobacter Infections - microbiology; Amino Acid Motifs; bacterial adhesion; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; biofilm; chaperone; gene regulation; Glycine - chemistry; Glycine - metabolism; Gram negative pathogen; Host Factor 1 Protein - chemistry; Host Factor 1 Protein - metabolism; Humans; intrinsically disordered protein; Microbiology; pathogen; Protein Stability; Protein Structure, Secondary; resistance; RNA binding protein; RNA, Bacterial - metabolism; RNA, Small Untranslated - metabolism; small RNA; Stress, Physiological; virulence factor; intrinsically disordered protein; chaperone; gene regulation; AbsR25; biofilm; RNA binding protein; pathogen; virulence factor; small RNA; bacterial adhesion; Gram negative pathogen; resistance
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA118.002921

Acinetobacter baumannii is a Gram-negative nosocomial pathogen that causes soft tissue infections in patients who spend a long time in intensive care units. This recalcitrant bacterium is very well known for developing rapid drug resistance, which is a combined outcome of its natural competence and mobile genetic elements. Successful efforts to treat these infections would be aided by additional information on the physiology of A. baumannii. Toward that end, we recently reported on a small RNA (sRNA), AbsR25, in this bacterium that regulates the genes of several efflux pumps. Because sRNAs often require the RNA chaperone Hfq for assistance in binding to their cognate mRNA targets, we identified and characterized this protein in A. baumannii. The homolog in A. baumannii is a large protein with an extended C terminus unlike Hfqs in other Gram-negative pathogens. The extension has a compositional bias toward glycine and, to a lower extent, phenylalanine and glutamine, suggestive of an intrinsically disordered region. We studied the importance of this glycine-rich tail using truncated versions of Hfq in biophysical assays and complementation of an hfq deletion mutant, finding that the tail was necessary for high-affinity RNA binding. Further tests implicate Hfq in important cellular processes of A. baumannii like metabolism, drug resistance, stress tolerance, and virulence. Our findings underline the importance of the glycine-rich C terminus in RNA binding, ribo-regulation, and auto-regulation of Hfq, demonstrating this hitherto overlooked protein motif to be an indispensable part of the A. baumannii Hfq.