Lethality of <i>Brucella microti</i> in a murine model of infection depends on the <i>wbkE</i> gene involved in O-polysaccharide synthesis

Ouahrani‐Bettache, Safia; Bagüés, María Pilar Jiménez de; Garza, Jorge de La; Freddi, Luca; Bueso, J.P.; Lyonnais, Sébastien; Dahouk, Sascha Al; Biase, Daniela De; Köhler, Stephan; Occhialini, Alessandra

doi:10.1080/21505594.2019.1682762

Cited by 11 publications

(7 citation statements)

References 45 publications

(58 reference statements)

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“…Beside the results for B. abortus and B. neotomae , published data obtained in bone marrow-derived macrophage survival assays are available for Brucella strain 83-210 (Jiménez de Bagues et al 2014 ) as well as for B. microti (Jiménez de Bagues et al 2010 ; Ouahrani-Bettache et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Survival of Brucella abortus S19 and other Brucella spp. in the presence of oxidative stress and within macrophages

2020

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The evolutionary “success” of the genus Brucella depends on the ability to persist both in the environment as well as inside of even activated macrophages of the animal host. For that, the Brucellae produce catalase and superoxide dismutase to defend against oxidative stress. Since the deletion of the mglA gene in the B. abortus S19 vaccine strain resulted not only in an increased tolerance to H2O2 but also in the induction of cytokines in macrophages, we here investigated the effect of oxidative stress (Fe2+ and H2O2) on the survival of B. abortus S19 and the isogenic B. abortus S 19 ∆mglA 3.14 deletion mutant in comparison with B. neotomae 5K33, Brucella strain 83/13, and B. microti CCM4915. These Brucellae belong to different phylogenetic clades and show characteristic differences in the mgl-operon. From the various Brucellae tested, B. abortus S19 showed the highest susceptibility to oxidative stress and the lowest ability to survive inside of murine macrophages. B. abortus S19 ∆mglA 3.14 as well as B. neotomae, which also belongs to the classical core clade of Brucella and lacks the regulators of the mgl-operon, presented the highest degree of tolerance to H2O2 but not in the survival in macrophages. The latter was most pronounced in case of an infection with B. 83/13 and B. microti CCM4915. The various Brucellae investigated here demonstrate significant differences in tolerance against oxidative stress and different survival in murine macrophages, which, however, do not correlate directly.

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Section: Discussionmentioning

confidence: 99%

Survival of Brucella abortus S19 and other Brucella spp. in the presence of oxidative stress and within macrophages

2020

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“…Its replication rate in murine and human macrophage cells is higher than that of classical species, and B. microti is the first Brucella species described to be lethal in mice (Jiménez De Bagüés et al, 2010). This lethal phenotype depends on the type IV secretion system VirB (Hanna et al, 2011) and, as we reported lately, on a smooth LPS with an intact O-polysaccharide (Ouahrani-Bettache et al, 2019). In contrast, at sub-lethal doses, B. microti is rapidly cleared from infected mice, never gives rise to chronic infection and confers protection.…”

Section: Introductionmentioning

confidence: 81%

Comparative Genome-Wide Transcriptome Analysis of Brucella suis and Brucella microti Under Acid Stress at pH 4.5: Cold Shock Protein CspA and Dps Are Associated With Acid Resistance of B. microti

et al. 2021

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Brucellae are facultative intracellular coccobacilli causing brucellosis, one of the most widespread bacterial zoonosis affecting wildlife animals, livestock and humans. The genus Brucella comprises classical and atypical species, such as Brucella suis and Brucella microti, respectively. The latter is characterized by increased metabolic activity, fast growth rates, and extreme acid resistance at pH 2.5, suggesting an advantage for environmental survival. In addition, B. microti is more acid-tolerant than B. suis at the intermediate pH of 4.5. This acid-resistant phenotype of B. microti may have major implications for fitness in soil, food products and macrophages. Our study focused on the identification and characterization of acid resistance determinants of B. suis and B. microti in Gerhardt’s minimal medium at pH 4.5 and 7.0 for 20 min and 2 h by comparative RNA-Seq-based transcriptome analysis, validated by RT-qPCR. Results yielded a common core response in both species with a total of 150 differentially expressed genes, and acidic pH-dependent genes regulated specifically in each species. The identified core response mechanisms comprise proton neutralization or extrusion from the cytosol, participating in maintaining physiological intracellular pH values. Differential expression of 441 genes revealed species-specific mechanisms in B. microti with rapid physiological adaptation to acid stress, anticipating potential damage to cellular components and critical energy conditions. Acid stress-induced genes encoding cold shock protein CspA, pseudogene in B. suis, and stress protein Dps were associated with survival of B. microti at pH 4.5. B. suis response with 284 specifically regulated genes suggested increased acid stress-mediated protein misfolding or damaging, triggering the set-up of repair strategies countering the consequences rather than the origin of acid stress and leading to subsequent loss of viability. In conclusion, our work supports the hypothesis that increased acid stress resistance of B. microti is based on selective pressure for the maintenance of functionality of critical genes, and on specific differential gene expression, resulting in rapid adaptation.

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Section: Introductionmentioning

confidence: 58%

Microbial Stress: From Model Organisms to Applications in Food, Microbiotechnology and Medicine

2022

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Lethality of Brucella microti in a murine model of infection depends on the wbkE gene involved in O-polysaccharide synthesis

Cited by 11 publications

References 45 publications

Survival of Brucella abortus S19 and other Brucella spp. in the presence of oxidative stress and within macrophages

Survival of Brucella abortus S19 and other Brucella spp. in the presence of oxidative stress and within macrophages

Comparative Genome-Wide Transcriptome Analysis of Brucella suis and Brucella microti Under Acid Stress at pH 4.5: Cold Shock Protein CspA and Dps Are Associated With Acid Resistance of B. microti

Microbial Stress: From Model Organisms to Applications in Food, Microbiotechnology and Medicine

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