Regulation of kinesin-1 activity by the <i>Salmonella enterica</i> effectors PipB2 and SifA

Alberdi, Lucrecia; Vergnes, Alexandra; Manneville, Jean‐Baptiste; Tembo, Dumizulu; Fang, Ziyan; Zhao, Yaya; Schroëder, Nina; Dumont, Audrey; Lagier, Margaux; Bassereau, Patricia; Redondo-Morata, Lorena; Gorvel, Jean‐Pierre; Méresse, Stéphane

doi:10.1242/jcs.239863

Cited by 14 publications

(16 citation statements)

References 52 publications

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“…This was confirmed by a live cell study showing that a ∆pipB2 mutant induces the formation of large, non-dynamic SITs [116]. In a recent study using immortalized macrophages from C57BL/6 wildtype or KIF5B -/mice, we showed that kinesin-1 also participates in the positioning of SCVs, keeping them in the juxtanuclear region but distant from the nucleus [117]. The molecular determinants of PipB2 that allow interaction with KLC are still unknown.…”

Section: Pipb2 Is a Linker For Kinesin-1supporting

confidence: 52%

Endomembrane remodeling and dynamics in Salmonella infection

Fang¹,

Méresse²

2022

Microb Cell

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Salmonellae are bacteria that cause moderate to severe infections in humans, depending on the strain and the immune status of the infected host. These pathogens have the particularity of residing in the cells of the infected host. They are usually found in a vacuolar compartment that the bacteria shape with the help of effector proteins. Following invasion of a eukaryotic cell, the bacterial vacuole undergoes maturation characterized by changes in localization, composition and morphology. In particular, membrane tubules stretching over the microtubule cytoskeleton are formed from the bacterial vacuole. Although these tubules do not occur in all infected cells, they are functionally important and promote intracellular replication. This review focuses on the role and significance of membrane compartment remodeling observed in infected cells and the bacterial and host cell pathways involved.

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Section: Pipb2 Is a Linker For Kinesin-1supporting

confidence: 52%

Endomembrane remodeling and dynamics in Salmonella infection

Fang¹,

Méresse²

2022

Microb Cell

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Section: Discussionmentioning

confidence: 99%

“…Salmonella employs SPI-2 encoded protein SpiC to inhibit the fusion of lysosomes with SCV [34]. Another SPI-2 protein, SifA, forms Salmonella -induced filaments in epithelial cells to maintain the integrity of SCV by downregulating the recruitment of kinesins [37, 38]. SifA interacts with Rab9 to block the retrograde transport of mannose-6-phosphate receptors and MPR hydrolases to the Golgi apparatus, which ultimately inhibits lysosomal fusion with SCV [39].…”

Section: Discussionmentioning

confidence: 99%

The extracellular loops of Salmonella Typhimurium outer membrane protein A (OmpA) maintain the stability of Salmonella containing vacuole (SCV) in murine macrophages and protect the bacteria from autophagy-dependent lysosomal degradation

Chowdhury

Hajra

Chakravortty

2021

Preprint

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After entering the host cells, Salmonella Typhimurium (STM) stays inside a modified membrane-bound compartment called Salmonella containing vacuole (SCV). The biogenesis and stability of SCV are crucial for the intracellular proliferation of Salmonella. Our research has provided a novel mechanistic view on the role of a bacterial porin OmpA in maintaining the stability of SCV. We found that the deletion of OmpA forces the bacteria to escape from the SCV during the immediate early stage of infection. In the absence of OmpA, the bacteria failed to retain the LAMP-1 and came into the host cell’s cytosol. Subsequently, the cytosolic population of STM ΔompA activated the host autophagy machinery after colocalizing with syntaxin 17 and LC3B. The autophagosomes carrying STM ΔompA were targeted to the lysosomes for degradation. Inhibition of autophagy pathway using bafilomycin A1 restored the intracellular proliferation of STM ΔompA. We further showed that the four extracellular loops of OmpA played a crucial role in holding the LAMP-1 pool around the SCV. We have altered the extracellular loop sequences of Salmonella OmpA by site-directed mutagenesis and observed that the bacteria failed to maintain the LAMP-1 pool around the SCV, which finally resulted in their release into the cytosol of the host macrophages. Surprisingly, the cytosolic population of Salmonella having mutations in the extracellular loops of OmpA didn’t activate the lysosomal degradation pathway like STM ΔompA, which helped them to survive within the murine macrophages. In summary, our study revealed an OmpA dependent novel strategy utilized by Salmonella to combat host autophagy by promoting the stability of SCV.

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“…Work performed by Boucrot et al determined SifA targeted SKIP, a host protein that down-regulates the recruitment of kinesin on the SCV (Boucrot et al, 2005). Recently, the SifA/SKIP complex has been shown to be necessary for the activation of the kinesin-1 recruited by PipB2, revealing a functional interaction important for formation of tubules in membrane exchange and nutrient supply (Alberdi et al, 2020). The SseK3 effector targets various host small GTPases (Gan et al, 2020).…”

Section: The Late Endosome-like Vacuole Of Salmonella Entericamentioning

confidence: 99%

Idiosyncratic Biogenesis of Intracellular Pathogens-Containing Vacuoles

Vaughn

Kwaik

2021

Front. Cell. Infect. Microbiol.

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While most bacterial species taken up by macrophages are degraded through processing of the bacteria-containing vacuole through the endosomal-lysosomal degradation pathway, intravacuolar pathogens have evolved to evade degradation through the endosomal-lysosomal pathway. All intra-vacuolar pathogens possess specialized secretion systems (T3SS-T7SS) that inject effector proteins into the host cell cytosol to modulate myriad of host cell processes and remodel their vacuoles into proliferative niches. Although intravacuolar pathogens utilize similar secretion systems to interfere with their vacuole biogenesis, each pathogen has evolved a unique toolbox of protein effectors injected into the host cell to interact with, and modulate, distinct host cell targets. Thus, intravacuolar pathogens have evolved clear idiosyncrasies in their interference with their vacuole biogenesis to generate a unique intravacuolar niche suitable for their own proliferation. While there has been a quantum leap in our knowledge of modulation of phagosome biogenesis by intravacuolar pathogens, the detailed biochemical and cellular processes affected remain to be deciphered. Here we discuss how the intravacuolar bacterial pathogens Salmonella, Chlamydia, Mycobacteria, Legionella, Brucella, Coxiella, and Anaplasma utilize their unique set of effectors injected into the host cell to interfere with endocytic, exocytic, and ER-to-Golgi vesicle traffic. However, Coxiella is the main exception for a bacterial pathogen that proliferates within the hydrolytic lysosomal compartment, but its T4SS is essential for adaptation and proliferation within the lysosomal-like vacuole.

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Regulation of kinesin-1 activity by the Salmonella enterica effectors PipB2 and SifA

Cited by 14 publications

References 52 publications

Endomembrane remodeling and dynamics in Salmonella infection

Endomembrane remodeling and dynamics in Salmonella infection

The extracellular loops of Salmonella Typhimurium outer membrane protein A (OmpA) maintain the stability of Salmonella containing vacuole (SCV) in murine macrophages and protect the bacteria from autophagy-dependent lysosomal degradation

Idiosyncratic Biogenesis of Intracellular Pathogens-Containing Vacuoles

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