Biology subjects

Bigelow, L.

Publications and source records attributed to Bigelow, L..

3 recordsLinked to original sources

bioRxiv2026

The ultrastructure of subarachnoid trabeculae in non-human primates varies by tissue region within the central nervous system

The subarachnoid space (SAS) plays an important role in central nervous system (CNS) physiology, housing cerebrospinal fluid (CSF), providing nutrients, clearing waste, and protecting CNS tissues from injury. The SAS also contains an intricate arrangement of collagenous fibers, known as subarachnoid trabeculae, which serve as biomechanical support for the subarachnoid space and modulate the flow of CSF. Despite their myriad of roles in health and disease, the ultrastructure of trabeculae is incompletely described, with a specific gap in understanding how fiber structure varies across different regions of the CNS. In this work, we used optimized fixation techniques and scanning electron microscopy (SEM) imaging to study ultrastructural differences in trabeculae that were obtained from different regions of the nonhuman primate (NHP) brain and spinal cord. Qualitative assessments included evaluation of the relative prevalence of different kinds of fiber networks by region, leading us to a redefinition of terminology for fiber morphology. Quantitative measurements yielded dramatic differences in fiber diameter, density, and network porosity between different regions of the CNS. Broadly, trabeculae supporting cauda equina, cervical spinal cord, and exiting nerve roots were observed to have a very high density of small diameter fibers, whereas larger fibers and more complex arrangements were observed in other regions of the CNS. These data contribute to a growing field understanding of CNS-region specific differences in tissue ultrastructure.

neuroscience↗

bioRxiv2019

Brucella EipB is periplasmic β-spiral protein required for envelope stress resistance and infection

The Gram-negative cell envelope is a remarkably diverse structure with core components that include an inner membrane, an outer membrane, and a peptidoglycan layer in the periplasmic space between. We show that a conserved DUF1849-family protein, EipB, is secreted to the periplasmic space of Brucella, a monophyletic group of intracellular pathogens. In the periplasm, EipB folds into an unusual fourteen-stranded {beta}-spiral structure that contains a conserved disulfide bond. EipB has structural features that resemble the LolA and LolB lipoprotein delivery system, though the overall topology and fold of EipB is distinct from LolA/LolB. Deletion of eipB results in defects in both cell envelope integrity in vitro and in maintenance of spleen colonization in a mouse model of B. abortus infection. Transposon disruption of ttpA, which encodes a periplasmic tetratricopeptide repeat (TPR) protein, is synthetically lethal with eipB deletion in B. abortus. ttpA is a known virulence determinant in B. melitensis, and our studies of ttpA deletion and overexpression strains provide evidence that ttpA, like eipB, contributes to cell envelope function in Brucella. We conclude that eipB and ttpA function in the Brucella periplasmic space to maintain cell envelope integrity and to facilitate survival in a mammalian host. ImportanceBrucella species cause brucellosis, a global zoonosis. A gene encoding a conserved uncharacterized protein, EipB, is present in all sequenced Brucella and several other genera in the class Alphaproteobacteria. To our knowledge, this study presents the first functional and structural characterization of a protein from the DUF1849 family, to which EipB belongs. EipB is secreted to the periplasm where it forms a spiral-like anti-parallel {beta} structure. Deletion of Brucella eipB results in defects of the cell envelope and in reduced virulence in an animal model of disease. eipB genetically interacts with ttpA, which also encodes a periplasmic protein. We propose that EipB and TtpA function as part of a system required for cell envelope homeostasis in select Alphaproteobacteria.

microbiology↗

bioRxiv2018

Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus

Molecular components of the Brucella abortus cell envelope play a major role in its ability to infect, colonize and survive inside mammalian host cells. In this study, we have defined a role for a conserved gene of unknown function in B. abortus envelope stress resistance and infection. Expression of this gene, which we name eipA, is directly activated by the essential cell cycle regulator, CtrA. eipA encodes a soluble periplasmic protein that adopts an unusual eight-stranded {beta}-barrel fold. Deletion of eipA attenuates replication and survival in macrophage and mouse infection models, and results in sensitivity to treatments that compromise the integrity of the cell envelope. Transposon disruption of genes required for LPS O-polysaccharide biosynthesis is synthetically lethal with eipA deletion. This genetic connection between O-polysaccharide and eipA is corroborated by our discovery that eipA is essential in Brucella ovis, a naturally rough species that harbors mutations in several genes required for O-polysaccharide production. Conditional depletion of eipA expression in B. ovis results in a cell chaining phenotype, providing evidence that eipA directly or indirectly influences cell division in Brucella. We conclude that EipA is a molecular determinant of Brucella virulence that functions to maintain cell envelope integrity and influences cell division.

microbiology↗