The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids

Rombouts, Yoann

doi:10.1172/jci168366

Cited by 4 publications

(1 citation statement)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To further confirm the effect of LysB FL in promoting a pro-inflammatory polarization of AMs, we assessed the intracellular accumulation of lipid droplets (LDs), which is associated to a pro-inflammatory phenotype 25,26 . We incubated mAMs with 15 nmol of either LysB FL or sfGFP for 3, 6, and 24 hours and stained intracellular LDs using Nile Red dye.…”

Section: Resultsmentioning

confidence: 99%

Endolysin B as a new archetype inM. tuberculosistreatment

Griego,

Antinori,

Spitaleri

et al. 2023

Preprint

View full text Add to dashboard Cite

SummarySo far it is thanks to antibiotics that illnesses, such as Tuberculosis (TB), are treatable. However, antimicrobial misuse combined withMycobacterium tuberculosisphenotypic plasticity are nullifying the effects of the existing therapies. As a result, increasingly people are dying (one person dies of TB every 20 seconds), especially due to the rise of multi-and extensively drug-resistant strains. There is indeed a urgent need for new and more effective therapies, which should match the requirement of avoiding the rise in drug resistance. Among them, the use of bacteriophage – bacteria-restricted viruses – or simply phage lytic enzyme (i.e.,endolysin) represents one of the most promising alternatives. All phages encode for the endolysin A (LysA), which degrades the bacteria cell wall, finally leading to the release of the newly synthesized virions. Nevertheless, mycobacteriophages (bacterial viruses selectively infecting mycobacteria), evolved the additional endolysin B (LysB) to selectively damage the complex mycobacteria cell wall, and to evade from their host. LysB, owing a lipolytic enzyme, can degrade the thick mycolic acid layer, and hence disrupt the integrity of the mycobacterial membrane. Despite its key role in mediating mycobacteria lysis, the molecular mechanism regulating LysB binding to its target remains poorly characterized. Herein, we selected Ms6LysB and created a fluorescent engineered version as a proxy to analyze LysB binding qualitatively and quantitatively to both the fast-growing non-pathogenicMycobacterium smegmatisand the slow-growing pathogenicM. tuberculosis.Additionally, we shed light on LysB antimicrobial activity uponM. tuberculosisinfection, by using alveolar-like mouse macrophages (mAMs) as a cellular model that closely recapitulates the natural niche ofM. tuberculosisinfection. Our study provides the proof-of-principle that Ms6 LysB binding to the outer mycobacterial membrane can impairM. tuberculosisgrowth homeostasis and that LysB retain its lytic properties even when internalized by mAMs. This lays the groundwork for the use of LysB as a new therapeutic strategy to undermineM. tuberculosisinfection.

show abstract

Section: Resultsmentioning

confidence: 99%