Characterization of a novel AraC/XylS-regulated family of N-acyltransferases in pathogens of the order Enterobacterales.

Autor: Belmont-Monroy L; Department of Pediatrics, University of Virginia School of Medicine and University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America.; Department of Public Health, UNAM School of Medicine and Federico Gomez Children's Hospital, Mexico City, Mexico., Saitz-Rojas W; Department of Pediatrics, University of Virginia School of Medicine and University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America., Soria-Bustos J; Department of Pediatrics, University of Virginia School of Medicine and University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America., Mickey AS; Department of Pediatrics, University of Virginia School of Medicine and University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America., Sherman NE; W. M. Keck Biomedical Mass Spectrometry Lab. University of Virginia, Charlottesville, Virginia, United States of America., Orsburn BC; W. M. Keck Biomedical Mass Spectrometry Lab. University of Virginia, Charlottesville, Virginia, United States of America., Ruiz-Perez F; Department of Pediatrics, University of Virginia School of Medicine and University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America., Santiago AE; Department of Pediatrics, University of Virginia School of Medicine and University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Aug 26; Vol. 16 (8), pp. e1008776. Date of Electronic Publication: 2020 Aug 26 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008776
Abstrakt: Enteroaggregative Escherichia coli (EAEC) is a diarrheagenic pathotype associated with traveler's diarrhea, foodborne outbreaks and sporadic diarrhea in industrialized and developing countries. Regulation of virulence in EAEC is mediated by AggR and its negative regulator Aar. Together, they control the expression of at least 210 genes. On the other hand, we observed that about one third of Aar-regulated genes are related to metabolism and transport. In this study we show the AggR/Aar duo controls the metabolism of lipids. Accordingly, we show that AatD, encoded in the AggR-regulated aat operon (aatPABCD) is an N-acyltransferase structurally similar to the essential Apolipoprotein N-acyltransferase Lnt and is required for the acylation of Aap (anti-aggregation protein). Deletion of aatD impairs post-translational modification of Aap and causes its accumulation in the bacterial periplasm. trans-complementation of 042aatD mutant with the AatD homolog of ETEC or with the N-acyltransferase Lnt reestablished translocation of Aap. Site-directed mutagenesis of the E207 residue in the putative acyltransferase catalytic triad disrupted the activity of AatD and caused accumulation of Aap in the periplasm due to reduced translocation of Aap at the bacterial surface. Furthermore, Mass spectroscopy revealed that Aap is acylated in a putative lipobox at the N-terminal of the mature protein, implying that Aap is a lipoprotein. Lastly, deletion of aatD impairs bacterial colonization of the streptomycin-treated mouse model. Our findings unveiled a novel N-acyltransferase family associated with bacterial virulence, and that is tightly regulated by AraC/XylS regulators in the order Enterobacterales.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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