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- Listeria monocytogenes Has Both Cytochrome bd-Type and Cytochrome aa(3)-Type Terminal Oxidases, Which Allow Growth at Different Oxygen Levels, and Both Are Important in InfectionPublication . Corbett, David; Goldrick, Marie; Fernandes, Vitor E.; Davidge, Kelly; Poole, Robert K.; Andrew, Peter W.; Cavet, Jennifer; Roberts, Ian S.Listeria monocytogenes is a foodborne pathogen responsible for a number of life-threatening infections of humans. During an infection, it invades epithelial cells before spreading from the intestine to the cells of the liver and spleen. This requires an ability to adapt to varying oxygen levels. Here, we demonstrate that L. monocytogenes has two terminal oxidases, a cytochrome bd-type (CydAB) and a cytochrome aa(3)-type menaquinol (QoxAB) oxidase, and that both are used for respiration under different oxygen tensions. Furthermore, we show that possession of both terminal oxidases is important in infection. In air, the CydAB bd-type oxidase is essential for aerobic respiration and intracellular replication, and cydAB mutants are highly attenuated in mice. In contrast, the QoxAB aa(3)-type oxidase is required neither for aerobic respiration in air nor for intracellular growth. However, the qoxAB mutants are attenuated in mice, with a delay in the onset of disease signs and with increased survival time, indicating a role for the QoxAB aa(3)-type oxidase in the initial stages of infection. Growth of bacteria under defined oxygen conditions revealed that at 1% (vol/vol), both oxidases are functional, and the presence of either is sufficient for aerobic respiration and intracellular replication. However, at 0.2% (vol/vol), both oxidases are necessary for maximum growth. These findings are consistent with the ability of L. monocytogenes to switch between terminal oxidases under different oxygen conditions, providing exquisite adaptation to different conditions encountered within the infected host.
- Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transectionPublication . Nogueira-Rodrigues, Joana; Leite, Sérgio C.; Pinto-Costa, Rita; Sousa, Sara C.; Luz, Liliana L.; Sintra, Maria A.; Oliveira, Raquel; Monteiro, Ana C.; Pinheiro, Gonçalo; Vitorino, Marta; Silva, Joana A.; S, Simão; Vitor Fernandes, Dr; Provazník, Jan; Benes, Vladimir; Cruz, Célia D.; Safronov, Boris V.; Magalhães, Ana; Reis, Celso A.; Vieira, Jorge; Vieira, Cristina P.; Tiscórnia, Gustavo; Araujo, Ines; Sousa, Mónica M.Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies beta 3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth.
- Coronal brain atlas in stereotaxic coordinates of the African spiny mouse, acomys cahirinusPublication . Vitorino, Marta; S, Simão; Moreira, João B.; Nogueira‐Rodrigues, Joana; Silva, Joana A; Sofia Lourenço, Ana; Vitor Fernandes, Dr; Sousa, Monica M.; Tiscornia, Gustavo; Araújo, Inês MariaThe African spiny mouse (Acomys cahirinus) is an emerging model of mammalian epimorphic regeneration that has aroused the interest of the scientific community in the last decade. To date, studies on brain repair have been hindered by the lack of knowledge on the neuroanatomy of this species. Here, we present a coronal brain atlas in stereotaxic coordinates, which allows for three-dimensional identification and localization of the brain structures of this species. The brain of 12-week-old spiny mice was mapped in stereotaxic coordinates using cresyl violet-stained brain sections obtained from coronal cryosectioning of the brain after transcardial perfusion with fixative. The atlas is presented in 42 plates representing sections spaced 240 mu m apart. Stereotaxic coordinates were validated using both a model of Parkinsonian lesion of the striatum with 6-hydroxydopamine and labeling of the corticospinal tract in the spiny mouse spinal cord using AAV1/2-GFP intracortical injections. This work presents a new tool in A. cahirinus neurobiology and opens new avenues of research for the investigation of the regenerative ability of A. cahirinus in models of brain disorders.
- The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infectionPublication . Fernandes, Vitor E.; Ercoli, Giuseppe; Bénard, Alan; Brandl, Carolin; Fahnenstiel, Hannah; Müller-Winkler, Jennifer; Weber, Georg F; Denny, Paul; Nitschke, Lars; Andrew, Peter WStreptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.