scholarly journals Treatment of infection-induced vascular pathologies is protective against persistent rough morphotype Mycobacterium abscessus infection in zebrafish

2021 ◽  
Author(s):  
Julia Y Kam ◽  
Kathryn Wright ◽  
Warwick J Britton ◽  
Stefan H Oehlers
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Abscessus ◽  
Granuloma Formation ◽  
Potential Host ◽  
Global Prevalence ◽  
Host Pathogen ◽  
Treatment Of Infection

Mycobacterium abscessus infections are of increasing global prevalence and are often difficult to treat due to complex antibiotic resistance profiles. While there are similarities between the pathogenesis of M. abscessus and tuberculous mycobacteria, including granuloma formation and stromal remodeling, there are distinct molecular differences at the host-pathogen interface. Here we have used a zebrafish-M. abscessus model and host-directed therapies that were previously identified in the zebrafish-M. marinum model to identify potential host-directed therapies against M. abscessus infection. We find efficacy of anti-angiogenic and vascular normalizing therapies against rough M. abscessus infection, but no effect of anti-platelet drugs.

scholarly journals Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

2016 ◽  
Vol 12 (11) ◽  
pp. e1005986 ◽  
Author(s):  
Audrey Bernut ◽  
Mai Nguyen-Chi ◽  
Iman Halloum ◽  
Jean-Louis Herrmann ◽  
Georges Lutfalla ◽  
...  
Keyword(s):  
Mycobacterium Abscessus ◽  
Granuloma Formation

scholarly journals Evaluation of the GenoType NTM-DR assay performance for the identification and molecular detection of antibiotic resistance in Mycobacterium abscessus complex

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0239146
Author(s):  
Nicolas Bouzinbi ◽  
Olivier Marcy ◽  
Thibault Bertolotti ◽  
Raphael Chiron ◽  
Pascale Bemer ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Molecular Detection ◽  
Mycobacterium Abscessus ◽  
Mycobacterium Abscessus Complex ◽  
Assay Performance

scholarly journals Mycobacterial HflX is a ribosome splitting factor that mediates antibiotic resistance

2019 ◽  
Vol 117 (1) ◽  
pp. 629-634 ◽  
Author(s):  
Paulami Rudra ◽  
Kelley R. Hurst-Hess ◽  
Katherine L. Cotten ◽  
Andrea Partida-Miranda ◽  
Pallavi Ghosh
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Smegmatis ◽  
Mycobacterium Abscessus ◽  
Macrolide Resistance ◽  
Gtp Hydrolysis ◽  
Ribosomal Subunits ◽  
Mutant Proteins ◽  
Splitting Factor

Antibiotic resistance in bacteria is typically conferred by proteins that function as efflux pumps or enzymes that modify either the drug or the antibiotic target. Here we report an unusual mechanism of resistance to macrolide-lincosamide antibiotics mediated by mycobacterial HflX, a conserved ribosome-associated GTPase. We show that deletion of thehflXgene in the pathogenicMycobacterium abscessus, as well as the nonpathogenicMycobacterium smegmatis, results in hypersensitivity to the macrolide-lincosamide class of antibiotics. Importantly, the level of resistance provided byMab_hflXis equivalent to that conferred byerm41, implying thathflXconstitutes a significant resistance determinant inM. abscessus. We demonstrate that mycobacterial HflX associates with the 50S ribosomal subunits in vivo and can dissociate purified 70S ribosomes in vitro, independent of GTP hydrolysis. The absence of HflX in aΔMs_hflXstrain also results in a significant accumulation of 70S ribosomes upon erythromycin exposure. Finally, a deletion of either the N-terminal or the C-terminal domain of HflX abrogates ribosome splitting and concomitantly abolishes the ability of mutant proteins to mediate antibiotic tolerance. Together, our results suggest a mechanism of macrolide-lincosamide resistance in which the mycobacterial HflX dissociates antibiotic-stalled ribosomes and rescues the bound mRNA. Given the widespread presence ofhflXgenes, we anticipate this as a generalized mechanism of macrolide resistance used by several bacteria.

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