Biology subjects

Soderstrom, B.

Publications and source records attributed to Soderstrom, B..

4 recordsLinked to original sources

bioRxiv2025

Molecular evolution of silver nanoparticle resistance in a bacterial pathogen and a unique adaptation response to ionic silver

This research explores the adaptive defense mechanisms of a nanosilver-resistant pathogen (NAgR) to protect and fight off the complex antimicrobial targeting of silver nanoparticles. The Gram-negative bacterium Acinetobacter baumannii upregulated expression of outer membrane proteins for cell surface defense, as well as membrane and capsule synthesis genes. Increased abundance of surface-attached biofilm colonies in NAgR was linked to the phenotypically indicated increase in membrane integrity, with the bacterium also forming more EPS, the biopolymer matrix that protects the residing colony. In response to the known reactive oxygen species (ROS) toxicity characteristics of the nanoparticle, NAgR upregulated its oxidative stress management system, specifically involving ROS scavenger enzymes and opportunistic metal efflux pumps. Many of these evolved defense mechanisms only manifested in the resistant bacterium, while they were absent in the wild-type strain. This study also details the unique defenses of an ionic silver-adapted A. baumannii variant, having evolved from the same wild-type parental strain as NAgR. Despite similarities in cell surface and biofilm defense trends, the slower-to-kill tolerant strain (AgT) exclusively upregulated multidrug efflux systems and respiratory chain enzymes, thought to maintain enhanced respiration activity, a known tolerant characteristic. Identification of these stable defense mechanisms can recommend strategies for molecular targeting to overcome the adaptation phenomena.

microbiology↗

bioRxiv2024

A simple ex vivo bladder infection model permits study of host-pathogen interactions in UTI

Urinary tract infections (UTI) are one of the most common infections, worldwide. To understand mechanisms of UTI pathogenesis and find new treatments, researchers often use animal models, such as mice or rats. However, studying certain phenotypes in animals can be difficult. Additionally, using animals in research comes with significant administrative and ethical challenges. To address these challenges, we developed a simple, reproducible, and cost-effective model to study UTI using donated mouse bladder tissue that would otherwise be discarded. This model allows researchers of all experience levels to study interactions between the host and pathogen in a controlled environment. We tested uropathogenic E. coli colonization and invasion of isolated urothelial sheets from 30 minutes to 24 hours, finding that bacterial burden in our ex vivo model was comparable to in vivo UTI mouse models. To optimize reproducibility, we tested multiple variables, including technical parameters, such as incubator conditions, and biological factors, such as biological sex or prior pregnancy in the donor mouse. This method offers several advantages, including assessment of early host-pathogen interactions, immune cell uptake of bacteria, the impact of age and sex of donor animals in infection, and diverse bacterial strains, mutants, or treatments. In addition, in some countries, sharing material recovered from animals sacrificed for other reasons does not require additional ethical approval by the receiving laboratory, providing a resource for labs without access to animals and reducing administrative burden. Given the breadth of the model with respect to sex, age, mouse and bacterial strain, and the ability to test any parameter that can be included in a 96-well plate, we believe this model will be useful to UTI researchers, with potential application beyond infection or even beyond the bladder to other tissues.

immunology↗

bioRxiv2024

Cell division protein A (CdpA) assembles and anchors the two FtsZ rings at midcell in haloarchaea

Many archaea appear to divide through the coordinated activities of two FtsZ homologues (FtsZ1 and FtsZ2) and another bacterial cell division homologue (SepF), which are part of the midcell division ring. Here, we identify an additional protein (HVO_0739, renamed CdpA) that is involved in cell division in Haloferax volcanii, with homologues in other Haloarchaea. CdpA localizes at the mid-cell division ring, and this requires the presence of the ring-assembly protein FtsZ1. The division constriction protein FtsZ2 also influenced the proper midcell assembly and structure of CdpA. In the absence of CdpA, cells frequently failed to divide properly, and FtsZ1 formed poorly condensed pseudo-helical structures spanning across a broad region of the cell, whereas FtsZ2 showed mispositioned foci, nano-rings, and filaments. The rate of directional movement of FtsZ1 and FtsZ2 structures around the division ring appeared minimally affected by loss of CdpA, which resulted in continual repositioning of the aberrant FtsZ structures in the cells. In contrast to the FtsZ proteins, CdpA formed relatively immobile foci around the ring. Protein domain function studies, pull-down assays, and multimer structure predictions suggest that CdpA is part of a membrane complex that tethers FtsZ2 and other division proteins to the midcell membrane. Our discovery of an archaeal FtsZ organisation and midcell anchor protein offers new insights into cell division mechanisms that are similar across the tree of life.

microbiology↗

bioRxiv2021

Dynamic localisation of DamX regulates bacterial filamentation and division during UPEC dispersal from host cells

Uropathogenic Escherichia coli (UPEC) cells can grow into highly filamentous forms during infection of bladder epithelial cells, but this process is poorly understood. Herein we found that some UPEC filaments released from infected bladder cells in vitro grew very rapidly and by more than 100 {micro}m before initiating division, whereas others did not survive, suggesting that filamentation is a stress response that promotes dispersal. The DamX bifunctional division protein, which is essential for UPEC filamentation, was initially non-localized but then assembled at multiple division sites in the filaments prior to division. DamX rings maintained consistent thickness during constriction and remained at the septum until after membrane fusion was completed, like in rod cell division. Our findings suggest a mechanism involving regulated dissipation of DamX, leading to division arrest and filamentation, followed by its reassembly into division rings to promote UPEC dispersal and survival during infection.

microbiology↗