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1. Anidulafungin liposome nanoparticles exhibit antifungal activity against planktonic and biofilm Candida albicans

   https://doi.org/10.1002/jbm.a.36984  

   Vera‐González, Noel ; Bailey‐Hytholt, Christina M. ; Langlois, Luc ; de Camargo Ribeiro, Felipe ; de Souza Santos, Evelyn Luzia ; Junqueira, Juliana Campos ; Shukla, Anita ( June 2020 , Journal of Biomedical Materials Research Part A)

   Fungal infections can cause significant patient morbidity and mortality. Nanoparticle therapeutics have the potential to improve treatment of these infections. Here we report the development of liposomal nanoparticles incorporating anidulafungin, a potent antifungal, with the goal of increasing its solubility and aiding in localization to fungi. Liposomes were fabricated with three concentrations of anidulafungin yielding monodisperse ~100 nm unilamellar vesicles. All three formulations inhibited planktonicCandida albicansgrowth at a minimum inhibitory concentration equivalent to free drug. All three formulations also disrupted preformedC. albicansbiofilms, reducing fungal burden by as much as 99%, exhibiting superior biofilm disruption compared with free drug. Liposome formulations tested in vivo inC. albicansinfectedGalleria mellonellawax moth larvae demonstrated increased survival compared to free drug equivalents, leading to a survival of 33 to 67% of larvae over 7 days depending on the liposome utilized compared with only 25% survival of larvae administered free drug. Liposomal formulations along with free anidulafungin did not cause red blood cell lysis. Ultimately, the liposome formulations reported here increased anidulafungin solubility, displayed promising efficacy against planktonic and biofilmC. albicans, and improved the survival ofC. albicans–infectedG. mellonellacompared to free anidulafungin.

    

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2. Both Pseudomonas aeruginosa and Candida albicans Accumulate Greater Biomass in Dual-Species Biofilms under Flow

   https://doi.org/10.1128/mSphere.00416-21  

   Kasetty, Swetha ; Mould, Dallas L. ; Hogan, Deborah A. ; Nadell, Carey D. ( June 2021 , mSphere)

   Mitchell, Aaron P. (Ed.)

   ABSTRACT Microbe-microbe interactions can strongly influence growth and biofilm formation kinetics. For Pseudomonas aeruginosa and Candida albicans , which are found together in diverse clinical sites, including urinary and intravenous catheters and the lungs of individuals with cystic fibrosis (CF), we compared the kinetics of biofilm formation by each species in dual-species and single-species biofilms. We engineered fluorescent protein constructs for P. aeruginosa (producing mKO-κ ) and C. albicans (producing mKate2 ) that did not alter growth and enabled single-cell resolution imaging by live-sample microscopy. Using these strains in an optically clear derivative of synthetic CF sputum medium, we found that both P. aeruginosa and C. albicans displayed increased biovolume accumulation—by three- and sixfold, respectively—in dual-species biofilms relative to single-species biofilms. This result was specific to the biofilm environment, as enhanced growth was not observed in planktonic cocultures. Stimulation of C. albicans biofilm formation occurred regardless of whether P. aeruginosa was added at the time of fungal inoculation or 24 h after the initiation of biofilm development. P. aeruginosa biofilm increases in cocultures did not require the Pel extracellular polysaccharide, phenazines, and siderophores known to influence C. albicans . P. aeruginosa mutants lacking Anr, LasR, and BapA were not significantly stimulated by C. albicans , but they still promoted a significant enhancement of biofilm development of the fungus, suggesting a fungal response to the presence of bacteria. Last, we showed that a set of P. aeruginosa clinical isolates also prompted an increase of biovolume by C. albicans in coculture. IMPORTANCE There is an abundance of work on both P. aeruginosa and C. albicans in isolation, and quite some work as well on the way these two microbes interact. These studies do not, however, consider biofilm environments under flow, and our results here show that the expected outcome of interaction between these two pathogens can actually be reversed under flow, from pure antagonism to an increase in biomass on the part of both. Our work also highlights the importance of cellular-scale spatial structure in biofilms for understanding multispecies population dynamics. 

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3. Vibrio cholerae filamentation promotes chitin surface attachment at the expense of competition in biofilms

   https://doi.org/10.1073/pnas.1819016116  

   Wucher, Benjamin R. ; Bartlett, Thomas M. ; Hoyos, Mona ; Papenfort, Kai ; Persat, Alexandre ; Nadell, Carey D. ( July 2019 , Proceedings of the National Academy of Sciences)

   Collective behavior in spatially structured groups, or biofilms, is the norm among microbes in their natural environments. Though biofilm formation has been studied for decades, tracing the mechanistic and ecological links between individual cell morphologies and the emergent features of cell groups is still in its infancy. Here we use single-cell–resolution confocal microscopy to explore biofilms of the human pathogen Vibrio cholerae in conditions mimicking its marine habitat. Prior reports have noted the occurrence of cellular filamentation in V. cholerae , with variable propensity to filament among both toxigenic and nontoxigenic strains. Using a filamenting strain of V. cholerae O139, we show that cells with this morphotype gain a profound competitive advantage in colonizing and spreading on particles of chitin, the material many marine Vibrio species depend on for growth in seawater. Furthermore, filamentous cells can produce biofilms that are independent of primary secreted components of the V. cholerae biofilm matrix; instead, filamentous biofilm architectural strength appears to derive at least in part from the entangled mesh of cells themselves. The advantage gained by filamentous cells in early chitin colonization and growth is countered in long-term competition experiments with matrix-secreting V. cholerae variants, whose densely packed biofilm structures displace competitors from surfaces. Overall, our results reveal an alternative mode of biofilm architecture that is dependent on filamentous cell morphology and advantageous in environments with rapid chitin particle turnover. This insight provides an environmentally relevant example of how cell morphology can impact bacterial fitness. 

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4. Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across Candida albicans Strains and Ploidy States

   https://doi.org/10.1128/mSphere.00433-20  

   Smith, Amanda C. ; Hickman, Meleah A. ( June 2020 , mSphere)

   Mitchell, Aaron P. (Ed.)

   ABSTRACT Candida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for C. albicans to adapt to changing or stressful environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, in which tetraploids arise via diploid mating or stress-induced mitotic defects and undergo nonmeiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to C. albicans genome instability in vitro or in the host environment. Here, we tested how genetic background, ploidy, and the host environment impacts C. albicans genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across C. albicans strain background and ploidy state. We then assessed if host-induced genomic changes resulted in fitness consequences on growth rate and nonlethal virulence phenotypes and found that many host-derived isolates significantly changed relative to their parental strain. Interestingly, diploid host-associated C. albicans predominantly decreased host reproductive fitness, whereas tetraploid host-associated C. albicans increased host reproductive fitness. Together, these results are important for understanding how host-induced genomic changes in C. albicans alter its relationship with the host. IMPORTANCE Candida albicans is an opportunistic fungal pathogen of humans. The ability to generate genetic variation is essential for adaptation and is a strategy that C. albicans and other fungal pathogens use to change their genome size. Stressful environments, including the host, induce C. albicans genome instability. Here, we investigated how C. albicans genetic background and ploidy state impact genome instability, both in vitro and in a host environment. We show that the host environment induces genome instability, but the magnitude depends on C. albicans genetic background. Furthermore, we show that tetraploid C. albicans is highly unstable in host environments and rapidly reduces in genome size. These reductions in genome size often resulted in reduced virulence. In contrast, diploid C. albicans displayed modest host-induced genome size changes, yet these frequently resulted in increased virulence. Such studies are essential for understanding how opportunistic pathogens respond and potentially adapt to the host environment. 

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5. A homogenization model for the rheology and local field statistics of suspensions of particles in yield stress fluids

   https://doi.org/10.1122/8.0000337  

   Kammer, Christoph ; Blackwell, Brendan ; Arratia, Paulo E. ; Ponte Castañeda, Pedro ( May 2022 , Journal of Rheology)

   We investigate the rheological behavior of athermal particle suspensions using experiments and theory. A generalized version of the homogenization estimates of Ponte Castañeda and Willis [J. Mech. Phys. Solids, 43(12), 1919–1951 (1995)] is presented for the effective viscosity of athermal suspensions accounting for additional microstructural features (e.g., polydispersity) via an empirical parameter, [Formula: see text]. For the case of identically sized spheres dispersed with statistical isotropy in a Newtonian fluid, the parameter [Formula: see text] is estimated from the results of Batchelor and Green [J. Fluid Mech. 56(2), 375–400 (1972)] for the Huggins coefficient. Predictions for the macroscopic viscosity are found to be in good agreement with measurements for monodisperse polymethyl methacrylate (PMMA) spheres in glycerol, as well as for the empirical Krieger–Dougherty equation for the shear viscosity. The proposed estimates have the added benefit that they can also be used to get information on the statistics of the stress and strain-rate fields in the fluid and particle phases. In addition, results for the effective shear viscosity are used in combination with the linear comparison method of Ponte Castañeda [J. Mech. Phys. Solids 39(1), 45–71 (1991)] to generate the corresponding estimates for the effective macroscopic behavior and field statistics of particle suspensions in (viscoplastic) yield stress fluids. Good agreement is also found between the theoretical estimates and experimental results for the effective yield and flow stress of suspensions with monodisperse PMMA spheres in Carbopol. Finally, it is argued that the results for the phase averages and fluctuations of the stress and strain-rate fields can be used to provide a physical interpretation for the parameter [Formula: see text] in terms of the polydispersity of the suspension and its implications for the percolation threshold.

    

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