Rifabutin Is Bactericidal against Intracellular and Extracellular Forms of Mycobacterium abscessus.

Johansen, MD; Daher, W; Roquet-Banères, F; Raynaud, C; Alcaraz, M; Maurer, FP; Kremer, L

Rifabutin Is Bactericidal against Intracellular and Extracellular Forms of Mycobacterium abscessus.

Johansen, MD Daher, W Roquet-Banères, F Raynaud, C Alcaraz, M Maurer, FP Kremer, L

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Publisher:: AMER SOC MICROBIOLOGY
Publication Type:: Journal Article
Citation:: Antimicrobial agents and chemotherapy, 2020, 64, (11)
Issue Date:: 2020-10-20

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Field	Value	Language
dc.contributor.author	Johansen, MD
dc.contributor.author	Daher, W
dc.contributor.author	Roquet-Banères, F
dc.contributor.author	Raynaud, C
dc.contributor.author	Alcaraz, M
dc.contributor.author	Maurer, FP
dc.contributor.author	Kremer, L
dc.date.accessioned	2021-01-14T05:40:34Z
dc.date.available	2021-03-22T18:03:09Z
dc.date.issued	2020-10-20
dc.identifier.citation	Antimicrobial agents and chemotherapy, 2020, 64, (11)
dc.identifier.issn	0066-4804
dc.identifier.issn	1098-6596
dc.identifier.uri	http://hdl.handle.net/10453/145437
dc.description.abstract	Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. In this context, rifabutin (RFB) has been shown to be active against M. abscessus and has raised renewed interest in using rifamycins for the treatment of M. abscessus pulmonary diseases. Here, we compared the in vitro and in vivo activity of RFB against the smooth and rough variants of M. abscessus, differing in their susceptibility profiles to several drugs and physiopathologial characteristics. While the activity of RFB is greater against rough strains than in smooth strains in vitro, suggesting a role of the glycopeptidolipid layer in susceptibility to RFB, both variants were equally susceptible to RFB inside human macrophages. RFB treatment also led to a reduction in the number and size of intracellular and extracellular mycobacterial cords. Furthermore, RFB was highly effective in a zebrafish model of infection and protected the infected larvae from M. abscessus-induced killing. This was corroborated by a significant reduction in the overall bacterial burden, as well as decreased numbers of abscesses and cords, two major pathophysiological traits in infected zebrafish. This study indicates that RFB is active against M. abscessus both in vitro and in vivo, further supporting its potential usefulness as part of combination regimens targeting this difficult-to-treat mycobacterium.
dc.format	Electronic-Print
dc.language	eng
dc.publisher	AMER SOC MICROBIOLOGY
dc.relation.ispartof	Antimicrobial agents and chemotherapy
dc.relation.isbasedon	10.1128/aac.00363-20
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Microbiology
dc.title	Rifabutin Is Bactericidal against Intracellular and Extracellular Forms of Mycobacterium abscessus.
dc.type	Journal Article
utslib.citation.volume	64
utslib.location.activity	United States
utslib.for	0605 Microbiology
utslib.for	1108 Medical Microbiology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2021-01-14T05:40:22Z
pubs.issue	11
pubs.publication-status	Published
pubs.volume	64
utslib.citation.issue	11

Abstract:

Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. In this context, rifabutin (RFB) has been shown to be active against M. abscessus and has raised renewed interest in using rifamycins for the treatment of M. abscessus pulmonary diseases. Here, we compared the in vitro and in vivo activity of RFB against the smooth and rough variants of M. abscessus, differing in their susceptibility profiles to several drugs and physiopathologial characteristics. While the activity of RFB is greater against rough strains than in smooth strains in vitro, suggesting a role of the glycopeptidolipid layer in susceptibility to RFB, both variants were equally susceptible to RFB inside human macrophages. RFB treatment also led to a reduction in the number and size of intracellular and extracellular mycobacterial cords. Furthermore, RFB was highly effective in a zebrafish model of infection and protected the infected larvae from M. abscessus-induced killing. This was corroborated by a significant reduction in the overall bacterial burden, as well as decreased numbers of abscesses and cords, two major pathophysiological traits in infected zebrafish. This study indicates that RFB is active against M. abscessus both in vitro and in vivo, further supporting its potential usefulness as part of combination regimens targeting this difficult-to-treat mycobacterium.

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http://hdl.handle.net/10453/145437