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1. Determinants of vector-borne avian pathogen occurrence in a mosaic of habitat fragmentation in California

   https://doi.org/10.1186/s13071-025-06742-x  

   Amaya-Mejia, Wilmer; Pavan, Lucas; Lilly, Marie; Swei, Andrea; Dirzo, Rodolfo; Sehgal, Ravinder_N_M (March 2025, Parasites & Vectors)

   Abstract BackgroundAs habitat fragmentation increases, ecological processes, including patterns of vector-borne pathogen prevalence, will likely be disrupted, but ongoing investigations are necessary to examine this relationship. Here, we report the differences in the prevalence of Lyme disease (Borrelia burgdorferisensu lato, s.l.) and haemoproteosis (Haemoproteusspp.) pathogens in avian populations of a fragmented habitat.B. burgdorferis.l. is a generalist pathogen that is transmitted byIxodes pacificusvectors in California, andHaemoproteusis an avian parasite transmitted byCulicoidesvectors. MethodsTo determine whether biotic (avian and mammalian abundance) or abiotic characteristics (patch size and water availability) correlated with infection prevalence change, we screened 176 birds sampled across seven sites in oak woodland habitat in northern California. ResultsWhile biotic factors correlated with an increase in both pathogens, infection prevalence ofHaemoproteusspp. was only associated with individual-level traits, specifically foraging substrate and diet, andB. burgdorferis.l. was associated with community-level characteristics, both total mammal and, specifically, rodent abundance. Proximity to water was the only abiotic factor found to be significant for both pathogens and reinforces the importance of water availability for transmission cycles. Larger patch sizes did not significantly affect infection prevalence ofHaemoproteus,but did increase the prevalence ofB. burgdorferi. ConclusionsThese results highlight that while environmental factors (specifically habitat fragmentation) have a limited role in vector-borne pathogen prevalence, the indirect impact to biotic factors (community composition) can have consequences for bothHaemoproteusandB. burgdorferiprevalence in birds. Given the pervasiveness of habitat fragmentation, our results are of broad significance. Graphical abstract 

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2. Multiple stochastic pathways in forced peptide-lipid membrane detachment

   https://doi.org/10.1038/s41598-018-36528-4  

   Utjesanovic, Milica; Matin, Tina R.; Sigdel, Krishna P.; King, Gavin M.; Kosztin, Ioan (January 2019, Scientific Reports)

   Abstract We have used high resolution AFM based dynamic force spectroscopy to investigate peptide-lipid membrane interactions by measuring the detachment (last-rupture) force distribution,P(F), and the corresponding force dependent rupture rate,k(F), for two different peptides and lipid bilayers. The measured quantities, which differed considerably for different peptides, lipid-membranes, AFM tips (prepared under identical conditions), and retraction speeds of the AFM cantilever, could not be described in terms of the standard theory, according to which detachment occurs along a single pathway, corresponding to a diffusive escape process across a free energy barrier. In particular, the prominent retraction speed dependence ofk(F) was a clear indication that peptide-lipid membrane dissociation occurs stochastically along several detachment pathways. Thereby, we have formulated a general theoretical approach for describingP(F) andk(F), by assuming that peptide detachment from lipid membranes occurs, with certain probability, along a few dominant diffusive pathways. This new method was validated through a consistent interpretation of the experimental data. Furthermore, we have found that for moderate retraction speeds at intermediate force values,k(F) exhibits catch-bond behavior (i.e. decreasing detachment rate with increasing force). According to the proposed model this behavior is due to the stochastic mixing of individual detachment pathways which do not convert or cross during rupture. To our knowledge, such catch-bond mechanism has not been proposed and demonstrated before for a peptide-lipid interaction. 

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3. Beyond bacterial paradigms: uncovering the functional significance and first biogenesis machinery of archaeal lipoproteins

   https://doi.org/10.1101/2024.08.27.609747  

   Hong, Yirui; Makarova, Kira S; Xu, Rachel; Pfeiffer, Friedhelm; Pohlschroder, Mechthild (August 2024, bioRxiv)

   Abstract Lipoproteins are major constituents of prokaryotic cell surfaces. In bacteria, lipoprotein attachment to membrane lipids is catalyzed by prolipoprotein diacylglyceryl transferase (Lgt). However, no Lgt homologs have been identified in archaea, suggesting the unique archaeal membrane lipids require distinct enzymes for lipoprotein lipidation. Here, we performedin silicopredictions for all major archaeal lineages and revealed a high prevalence of lipoproteins across the domain Archaea. Using comparative genomics, we identified the first set of candidates for archaeal lipoprotein biogenesis components (Ali). Genetic and biochemical characterization confirmed two paralogous genes,aliAandaliB, are important for lipoprotein lipidation in the archaeonHaloferax volcanii. Disruption of AliA- and AliB-mediated lipoprotein lipidation results in severe growth defects, decreased motility, and cell-shape alterations, underscoring the importance of lipoproteins in archaeal cell physiology. AliA and AliB also exhibit different enzymatic activities, including potential substrate selectivity, uncovering a new layer of regulation for prokaryotic lipoprotein lipidation. 

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4. Organization and replicon interactions within the highly segmented genome of Borrelia burgdorferi

   https://doi.org/10.1371/journal.pgen.1010857  

   Ren, Zhongqing; Takacs, Constantin N.; Brandão, Hugo B.; Jacobs-Wagner, Christine; Wang, Xindan (July 2023, PLOS Genetics)

   Boccard, Frederic (Ed.)

   Borrelia burgdorferi, a causative agent of Lyme disease, contains the most segmented bacterial genome known to date, with one linear chromosome and over twenty plasmids. How this unusually complex genome is organized, and whether and how the different replicons interact are unclear. We recently demonstrated thatB.burgdorferiis polyploid and that the copies of the chromosome and plasmids are regularly spaced in each cell, which is critical for faithful segregation of the genome to daughter cells. Regular spacing of the chromosome is controlled by two separate partitioning systems that involve the protein pairs ParA/ParZ and ParB/Smc. Here, using chromosome conformation capture (Hi-C), we characterized the organization of theB.burgdorferigenome and the interactions between the replicons. We uncovered that although the linear chromosome lacks contacts between the two replication arms, the two telomeres are in frequent contact. Moreover, several plasmids specifically interact with the chromosomeoriCregion, and a subset of plasmids interact with each other more than with others. We found that Smc and the Smc-like MksB protein mediate long-range interactions on the chromosome, but they minimally affect plasmid-chromosome or plasmid-plasmid interactions. Finally, we found that disruption of the two partition systems leads to chromosome restructuring, correlating with the mis-positioning of chromosomeoriC. Altogether, this study revealed the conformation of a complex genome and analyzed the contribution of the partition systems and SMC family proteins to this organization. This work expands the understanding of the organization and maintenance of multipartite bacterial genomes. 

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5. Modulation of a protein-folding landscape revealed by AFM-based force spectroscopy notwithstanding instrumental limitations

   https://doi.org/10.1073/pnas.2015728118  

   Edwards, Devin T.; LeBlanc, Marc-Andre; Perkins, Thomas T. (March 2021, Proceedings of the National Academy of Sciences)

   Single-molecule force spectroscopy is a powerful tool for studying protein folding. Over the last decade, a key question has emerged: how are changes in intrinsic biomolecular dynamics altered by attachment to μm-scale force probes via flexible linkers? Here, we studied the folding/unfolding of α₃D using atomic force microscopy (AFM)–based force spectroscopy. α₃D offers an unusual opportunity as a prior single-molecule fluorescence resonance energy transfer (smFRET) study showed α₃D’s configurational diffusion constant within the context of Kramers theory varies with pH. The resulting pH dependence provides a test for AFM-based force spectroscopy’s ability to track intrinsic changes in protein folding dynamics. Experimentally, however, α₃D is challenging. It unfolds at low force (<15 pN) and exhibits fast-folding kinetics. We therefore used focused ion beam–modified cantilevers that combine exceptional force precision, stability, and temporal resolution to detect state occupancies as brief as 1 ms. Notably, equilibrium and nonequilibrium force spectroscopy data recapitulated the pH dependence measured using smFRET, despite differences in destabilization mechanism. We reconstructed a one-dimensional free-energy landscape from dynamic data via an inverse Weierstrass transform. At both neutral and low pH, the resulting constant-force landscapes showed minimal differences (∼0.2 to 0.5k_BT) in transition state height. These landscapes were essentially equal to the predicted entropic barrier and symmetric. In contrast, force-dependent rates showed that the distance to the unfolding transition state increased as pH decreased and thereby contributed to the accelerated kinetics at low pH. More broadly, this precise characterization of a fast-folding, mechanically labile protein enables future AFM-based studies of subtle transitions in mechanoresponsive proteins. 

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