The genome sequence of the facultative intracellular pathogen
            <i>Brucella melitensis</i>

DelVecchio, Vito G.; Kapatral, Vinayak; Redkar, Rajendra J.; Patra, Guy; Mujer, Cesar V.; Los, Tamara; Ivanova, Natalia; Anderson, Iain; Bhattacharyya, Anamitra; Lykidis, Athanasios; Reznik, Gary; Jabloński, L; Larsen, Niels; D’Souza, Mark; Bernal, Axel; Mazur, Mikhail; Goltsman, Eugene; Selkov, Eugene; Elzer, Philip H.; Hagius, Sue D.; O’Callaghan, David; Letesson, Jean‐Jacques; Haselkorn, Robert; Kyrpides, Nikos C.; Overbeek, Ross

doi:10.1073/pnas.221575398

Cited by 507 publications

(371 citation statements)

References 34 publications

(28 reference statements)

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“…The 1496 bp KpnI-SacI PCR fragment spanned a site located 25 bp upstream of the 5' end of znuA to a position 450 bp downstream from the 3' end [6] and amplified using primers 5'-GGTACCCCGGCTTGAGAATATGCAGCG-3' (KpnI site underlined) and 5'-GAGCTCCGTTGCCTGCCACG-GAAAGGG-3' (SacI site underlined).…”

Section: Meterials and Methodsmentioning

confidence: 99%

“…In Eschrerichia coli, two systems, a high-affinity system and a low-affinity system, have been described for zinc uptake [2,17], and the high-affinity zinc uptake system of Salmonella enterica serovar Typhimurium is important for virulence in mouse model [3]. However, B. abortus does not contain low-affinity zinc uptake system [6] and high-affinity zinc uptake system is still not understood.…”

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confidence: 99%

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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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Section: Meterials and Methodsmentioning

confidence: 99%

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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“…Distinction between species and biovars is currently performed by differential laboratory tests [3,27]. Although it has been proposed that the Brucella species should be grouped as biovars of a single species based on DNA-DNA hybridization studies [71] and on the comparison of the genome of B. melitensis [30] and B. suis [58], the current classification of brucellae in species according to differences in host preference and in pathogenicity should be preferred [23,53].…”

Section: Brucellae Taxonomymentioning

confidence: 99%

From the discovery of the Malta fever?s agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis

et al. 2005

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-Brucellosis is not a sustainable disease in humans. The source of human infection always resides in domestic or wild animal reservoirs. The routes of infection are multiple: foodborne, occupational or recreational, linked to travel and even to bioterrorism. New Brucella strains or species may emerge and existing Brucella species adapt to changing social, cultural, travel and agricultural environment. Brucella melitensis is the most important zoonotic agent, followed by Brucella abortus and Brucella suis. This correlates with the fact that worldwide, the control of bovine brucellosis (due to B. abortus) has been achieved to a greater extent than the control of sheep and goat brucellosis (due to B. melitensis), these latter species being the most important domestic animals in many developing countries. The long duration and high cost of treatment of human brucellosis reduces the efficacy of the therapy. There is no human vaccine for brucellosis and the occurrence of brucellosis is directly linked to the status of animal brucellosis in a region. In this context, the Word Health Organization has defined the development of a human vaccine, besides the implementation of control and eradication programs in animals, as a high priority. The pathogenicity for humans of B. suis biovars 1, 3 and 4 is well established, whereas B. suis biovar 2 seems to be less pathogenic. Indeed, although hunters and pig farmers have repeatably experienced infectious contact with B. suis biovar 2 (found in wild boar and outdoor-rearing pigs in Europe), isolation of B. suis biovar 2 from human samples have only been seldom reported. Marine mammal brucellosis, due to two new proposed Brucella species i.e. B. cetaceae and B. pinnipediae, represents a new zoonotic threat but the pathogenicity for humans of the different Brucella species found in cetaceans and pinnipeds still has to be clearly established.Brucella / animal and human brucellosis / zoonoses / domestic and wildlife reservoir

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“…More recent study showed that BMEI0216 gene of B. melitensis is required for internalization in HeLa cells [14]. Essential genes encoding invasins and adhesins have been identified by Brucella genome analysis, but those molecules have not been investigated on Brucella surface [15]. Brucella LPS has been recognized as an important virulence factor involved in bacterial adhesion and internalization [16].…”

Section: Introductionmentioning

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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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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The genome sequence of the facultative intracellular pathogen Brucella melitensis

Cited by 507 publications

References 34 publications

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

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

From the discovery of the Malta fever?s agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis

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

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