Rifabutin Is Inactivated by Mycobacterium abscessus Arr

Daniel Schäfle; Petra Selchow; Barbara Borer; Michael Meuli; Anna Rominski; Bettina Schulthess; Peter Sander

doi:10.1128/AAC.02215-20

Rifabutin Is Inactivated by Mycobacterium abscessus Arr

Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02215-20. doi: 10.1128/AAC.02215-20. Print 2021 Feb 17.

Authors

Daniel Schäfle¹, Petra Selchow¹, Barbara Borer¹, Michael Meuli¹, Anna Rominski¹, Bettina Schulthess^{1

2}, Peter Sander^{3

2}

Affiliations

¹ Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
² National Center for Mycobacteria, University of Zurich, Zurich, Switzerland.
³ Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland [email protected].

Abstract

Mycobacterium abscessus exhibits Arr (ADP-ribosyltransferase)-dependent rifampin resistance. In apparent contrast, rifabutin (RBT) has demonstrated promising activity in M. abscessus infection models, implying that RBT might not be inactivated by Arr. RBT susceptibility testing of M. abscessusΔarr revealed a strongly decreased MIC. Our findings suggest that the efficacy of RBT might be enhanced by rendering RBT resilient to Arr-dependent modification or by blocking M. abscessus Arr activity.

Keywords: ADP-ribosyltransferase; Mycobacterium; Mycobacterium abscessus; cystic fibrosis; resistance; rifabutin; rifampicin; rifamycin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADP Ribose Transferases
Humans
Microbial Sensitivity Tests
Mycobacterium Infections, Nontuberculous* / drug therapy
Mycobacterium abscessus* / genetics
Rifabutin / pharmacology
Rifampin / pharmacology

Substances

Rifabutin
ADP Ribose Transferases
Rifampin