Membrane sorting during swimming internalization of Brucella is required for phagosome trafficking decisions

Kim, Suk; Watarai, Masahisa; Makino, Sou Ichi; Shirahata, Toshikazu

doi:10.1006/mpat.2002.0531

Cited by 39 publications

(35 citation statements)

References 30 publications

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“…Among these molecules, PI3-kinase is known to be involved in phagocytosis and phagosome maturation [25]. However, controversial results have been reported regarding the role of PI3-kinase in Brucella phagocytosis [4,26,27]. Our results revealed that PI3-kinase is essential for smooth, but not rough B. abortus uptake by murine macrophage J774.A1, suggesting that uptake mechanisms of smooth and rough Brucella are different in these cells.…”

Section: Discussionmentioning

confidence: 58%

“…Reports of the effect of PI3-kinase on Brucella uptake have been controversial. Guzman-Verri et al reported that PI3-kinase is involved in the uptake of Brucella S2308 by HeLa cells [4], while others showed that wortmannin (PI3-kinase inhibitor) treatment did not inhibit wild type Brucella uptake [26,27]. To determine the roles of PI3-kinase in the uptake of smooth and rough B. abortus, J774.A1 macrophages were treated with 100 nM of wortmannin before Brucella infection.…”

Section: Effect Of Pi3-kinase Inhibitors On the Invasion Of Smooth Anmentioning

confidence: 99%

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Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Pei

Turse

Ficht

2008

Microbes and Infection

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Smooth Brucella abortus S2308 is virulent while rough derivatives are attenuated. Intracellular killing is often blamed for these differences. In the studies described, uptake kinetics and interaction of S2308 and S2308 manBA::Tn5 (CA180) rough mutants with macrophages were investigated. The results revealed that smooth B. abortus was rapidly internalized, achieving a maximum level in less than 5 minutes without additional uptake over the next 30 minutes. In contrast, continued uptake of the rough mutant was observed and only achieves a maximum level after 30 minutes. The results were confirmed by the differences in F-actin polymerization, lipid raft staining, early endosome colocalization and electron microscopic observations after smooth and rough Brucella infection. We also demonstrated for the first time that uptake of S2308, but not rough mutant CA180 was PI3-kinase and toll-like receptor 4 (TLR4) dependent. Differences in uptake were associated with differences in macrophage activation with regard to NF-κB translocation and cytokine production. These results provide evidence that the presence of B. abortus OPS dictates the interactions between Brucella and specific cell surface receptors minimizing macrophage activation and enhancing Brucella survival and/or persistence.

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Section: Discussionmentioning

confidence: 58%

Section: Effect Of Pi3-kinase Inhibitors On the Invasion Of Smooth Anmentioning

confidence: 99%

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Pei

Turse

Ficht

2008

Microbes and Infection

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“…However, PI3K inhibitors wortmannin (WTM) [16,17] and/or LY294002 [18] prevent phagocytosis of zymosan [19], α v β 3 -mediated uptake of apoptotic cells [20], and in some cases, particle ingestion via CD11b/CD18 [19,[21][22][23]. Conversely, WTM and LY294002 do not prevent ingestion of yeast, Escherichia coli, Yersinia enterocolitica, Legionella pneumophilia, Salmonella, or Brucella by macrophages [22][23][24][25][26]. PI3K is also dispensable for phagocytosis in Dictyostelium discoideum [27], and depletion of PI3Kα does not prevent engulfment of Mycobacterium tuberculosis [28].…”

Section: Introductionmentioning

confidence: 99%

Phosphoinositide3-kinase regulates actin polymerization during delayed phagocytosis ofHelicobacter pylori

Allen

Allgood

Han

et al. 2005

Journal of Leukocyte Biology

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We have shown previously that ulcerogenic (type I) strains of Helicobacter pylori (Hp) retard their entry into macrophages. However, the signaling pathways that regulate Hp phagocytosis are largely undefined. We show here that Hp strongly activated class IA phosphoinositide3-kinases (PI3Ks) in macrophages, coincident with phagocytosis, and endogenous p85 and active protein kinase Bα accumulated on forming phagosomes. PI3K inhibitors, wortmannin and LY294002, inhibited phagocytosis of Hp in a dose-dependent manner, and blockade of engulfment correlated directly with loss of 3′-phosphoinositides in the membrane subjacent to attached bacteria. During uptake of large immunoglobulin G (IgG)-coated particles, PI3Ks regulate pseudopod extension and phagosome closure. In marked contrast, we show here that 3′-phosphoinositides regulated actin polymerization at sites of Hp uptake. Moreover, Hp and IgG beads activated distinct PI3K isoforms. Phagosomes containing IgG-coated particles accumulated 3′-phosphatase and tensin homologue deleted on chromosome 10 and Src homology 2 domain-containing inositol 5′-phosphatase, yet Hp phagosomes did not. Finally, rapid uptake of IgG-opsonized Hp or a less-virulent type II Hp was PI3K-independent. We conclude that Hp and IgG beads are ingested by distinct mechanisms and that PI3Ks regulate the actin cytoskeleton during slow phagocytosis of ulcerogenic Hp.

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“…This operon is composed of 13 open reading frames (ORFs) that share homology with other bacterial type IV secretion systems in the intracellular trafficking of pathogens. Deletion or polar and non-polar mutations of these ORFs were not able to replicate and survive within phagocytes [19,21], and internalization and uptake pathway in phagosome trafficking between wildtype and virB mutant showed different patterns [11]. Thus, the VirB proteins of B. abortus are thought to be constituents of the secretion apparatus.…”

mentioning

confidence: 99%

Zinc Uptake System (znuA Locus) of Brucella abortus is Essential for Intracellular Survival and Virulence in Mice

Kim

Watanabe

Shirahata

et al. 2004

The Journal of Veterinary Medical Science

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ABSTRACT. Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and nonprofessional phagocytes, and cause abortion in domestic animals and undulant fever in humans. The mechanism and factors of virulence are not fully understood. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B. abortus, but contributes to utilization of zinc required for intracellular growth. KEY WORDS: Brucella abortus, intracellular growth, zinc, znuA.J. Vet. Med. Sci. 66(9): 1059-1063, 2004 Brucella abortus, a facultative, gram-negative, intracellular pathogen, is the etiologic agent of brucellosis, a widely distributed zoonosis [22]. The establishment of chronic infection depends on the ability of brucellae to survive within phagocytes [9]. In contrast to other intracellular pathogens, Brucella species do not produce exotoxins, antiphagocytic capsules or thick cell walls, resistance forms or fimbriae and do not show antigenic variation [7]. Intracellular survival and replication are key virulence features of Brucella because mutants defective for these attributes are also avirulent [10,14]. A key aspect of the virulence of Brucella successfully bypasses the bactericidal effects of phagocytes, and their virulence and chronic infections are thought to be due to their ability to avoid the killing mechanisms within host cells [5,20].The genetic basis of Brucella virulence is still poorly understood. The VirB type IV secretion system of Brucella has been identified recently [16]. This operon is composed of 13 open reading frames (ORFs) that share homology with other bacterial type IV secretion systems in the intracellular trafficking of pathogens. Deletion or polar and non-polar mutations of these ORFs were not able to replicate and survive within phagocytes [19,21], and internalization and uptake pathway in phagosome trafficking between wildtype and virB mutant showed different patterns [11]. Thus, the VirB proteins of B. abortus are thought to be constituents of the secretion apparatus. The genus Brucella does not contain plasmids naturally, and it is therefore possible that the proteins encoded by virB genes are involved in protein secretion rather than conjugation. A possible role in virulence is to inject effector molecules, which help in the establishment of replication niche into the host cell.Zinc plays an important role in living organism...

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Membrane sorting during swimming internalization of Brucella is required for phagosome trafficking decisions

Cited by 39 publications

References 30 publications

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Phosphoinositide3-kinase regulates actin polymerization during delayed phagocytosis ofHelicobacter pylori

Zinc Uptake System (znuA Locus) of Brucella abortus is Essential for Intracellular Survival and Virulence in Mice

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