Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine

Köster, Stefan; Klevorn, Thaís; Papavinasasundaram, Kadamba; Sassetti, Christopher M.; Portal-Celhay, Cynthia; Philips, Jennifer A.

doi:10.1016/j.vaccine.2018.01.012

Cited by 10 publications

(13 citation statements)

References 19 publications

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“…The Δ esxG , Δ esxH , and Δ pe4-ppe5 (Δ ppe ) mutants and complementing plasmids were previously described in detail ( 41 , 42 ). Previously, we showed that mc 2 6230 exhibits reduced LC3 trafficking compared to mc 2 6206, consistent with the reduction in xenophagy described for ESX-1 mutants ( 71 ). Strains were grown at 37°C in 7H9 medium (Middlebrook 7H9 broth; Difco) supplemented with 0.05% Tween 80 (Sigma), BBL Middlebrook OADC (oleic acid-albumin-dextrose-catalase) enrichment, and 0.2% glycerol (Sigma).…”

Section: Methodssupporting

confidence: 88%

“…The following M. tuberculosis strains were used in this study: H37Rv (WT), the Δ esxA mutant ( 32 ), the Δ esxG mutant (mc 2 7789), the Δ esxG complement (mc 2 7789 with pYUB1335), the Δ esxH mutant (mc 2 7846), the Δ pe4-ppe5 (Δ ppe ) mutant (mc 2 7848), the Δ esxH complement (mc 2 7846 containing pJP130), mc 2 6206 (Δ leuCD Δ panCD ), and mc 2 6230 (Δ RD1 Δ panCD ). The Δ esxA mutant, mc 2 6206, and mc 2 6230 were provided by William Jacobs, Jr. (Albert Einstein College of Medicine), and have also been previously characterized by our laboratory ( 32 , 52 , 53 , 71 ). The Δ esxG , Δ esxH , and Δ pe4-ppe5 (Δ ppe ) mutants and complementing plasmids were previously described in detail ( 41 , 42 ).…”

Section: Methodsmentioning

confidence: 99%

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Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage Response

Mittal

Skowyra

Uwase

et al. 2018

mBio

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Mycobacterium tuberculosis causes tuberculosis, which kills more people than any other infection. M. tuberculosis grows in macrophages, cells that specialize in engulfing and degrading microorganisms. Like many intracellular pathogens, in order to cause disease, M. tuberculosis damages the membrane-bound compartment (phagosome) in which it is enclosed after macrophage uptake. Recent work showed that when chemicals damage this type of intracellular compartment, cells rapidly detect and repair the damage, using machinery called the endosomal sorting complex required for transport (ESCRT). Therefore, we hypothesized that ESCRT might also respond to pathogen-induced damage. At the same time, our previous work showed that the EsxG-EsxH heterodimer of M. tuberculosis can inhibit ESCRT, raising the possibility that M. tuberculosis impairs this host response. Here, we show that ESCRT is recruited to damaged M. tuberculosis phagosomes and that EsxG-EsxH undermines ESCRT-mediated endomembrane repair. Thus, our studies demonstrate a battle between host and pathogen over endomembrane integrity.

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Section: Methodssupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage Response

Mittal

Skowyra

Uwase

et al. 2018

mBio

Self Cite

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“…M. tuberculosis is recognized and phagocytosed by macrophages via different surface receptors, including TLRs, mannose receptors and complement receptors ( Schlesinger, 1993 ; Yu et al., 2014 ). Even though M. tuberculosis has been shown to be targeted by LAP, it is still not clear which fraction of phagosomes progresses to LAPosomes and whether this process enhances the ability of phagocytes to clear the pathogen or it is exploited by the pathogen for its intracellular survival ( Köster et al., 2017 ; Köster et al., 2018 ).…”

Section: Interactions Of Bacterial Pathogens With Lapmentioning

confidence: 99%

“…LAP resistance of M. tuberculosis was found to be mediated by the virulence factor CpsA, which prevents recruitment of NOX2 to the pathogen-containing phagosome ( Köster et al., 2017 ; Köster et al., 2018 ). While the inactivation of NOX2 by CpsA resulted in impaired lysosomal trafficking, reduced phagolysosome biogenesis and ultimately the survival and proliferation of intracellular M. tuberculosis , the deletion of CpsA in M. tuberculosis resulted in efficient degradation of the pathogen by LAP.…”

Section: Interactions Of Bacterial Pathogens With Lapmentioning

confidence: 99%

LAPped in Proof: LC3‐Associated Phagocytosis and the Arms Race Against Bacterial Pathogens

Grijmans

Kooij

Varela

et al. 2022

Front. Cell. Infect. Microbiol.

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Cells of the innate immune system continuously patrol the extracellular environment for potential microbial threats that are to be neutralized by phagocytosis and delivery to lysosomes. In addition, phagocytes employ autophagy as an innate immune mechanism against pathogens that succeed to escape the phagolysosomal pathway and invade the cytosol. In recent years, LC3-associated phagocytosis (LAP) has emerged as an intermediate between phagocytosis and autophagy. During LAP, phagocytes target extracellular microbes while using parts of the autophagic machinery to label the cargo-containing phagosomes for lysosomal degradation. LAP contributes greatly to host immunity against a multitude of bacterial pathogens. In the pursuit of survival, bacteria have developed elaborate strategies to disarm or circumvent the LAP process. In this review, we will outline the nature of the LAP mechanism and discuss recent insights into its interplay with bacterial pathogens.

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“…In addition, microtubule-associated protein 1A/1B-light chain 3 (LC3) related phagocytosis and autophagy enhance antigen presentation and may contribute to vaccine efficacy, while Mtb can inhibit above effects. And BCG vaccine strain elicits even less LC3-trafficking than Mtb, which may explain its limited efficacy ( 50 ). Köster et al knocked out the CpsA gene which could inhibit LC3 traffic pathways from mc26206 vaccine strain (ΔCpsA) and inoculated mice.…”

Section: Bcg Vaccinesmentioning

confidence: 99%

Advance in strategies to build efficient vaccines against tuberculosis

Guo²,

Xu³

et al. 2022

Front. Vet. Sci.

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Tuberculosis is a chronic consumptive infectious disease, which can cause great damage to human and animal health all over the world. The emergence of multi-drug resistant strains, the unstable protective effect of Bacillus Calmette-Guérin (BCG) vaccine on adults, and the mixed infection with HIV all warn people to exploit new approaches for conquering tuberculosis. At present, there has been significant progress in developing tuberculosis vaccines, such as improved BCG vaccine, subunit vaccine, DNA vaccine, live attenuated vaccine and inactivated vaccine. Among these candidate vaccines, there are some promising vaccines to improve or replace BCG vaccine effect. Meanwhile, the application of adjuvants, prime-boost strategy, immunoinformatic tools and targeting components have been studied concentratedly, and verified as valid means of raising the efficiency of tuberculosis vaccines as well. In this paper, the latest advance in tuberculosis vaccines in recent years is reviewed to provide reliable information for future tuberculosis prevention and treatment.

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Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine

Cited by 10 publications

References 19 publications

Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage Response

Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage Response

LAPped in Proof: LC3‐Associated Phagocytosis and the Arms Race Against Bacterial Pathogens

Advance in strategies to build efficient vaccines against tuberculosis

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