Extracellular DNAses Facilitate Antagonism and Coexistence in Bacterial Competitor-Sensing Interference Competition.

Over the last 4 decades, the rate of discovery of novel antibiotics has decreased drastically, ending the era of fortuitous antibiotic discovery. A better understanding of the biology of bacteriogenic toxins potentially helps to prospect for new antibiotics. To initiate this line of research, we quantified antagonists from two different sites at two different depths of soil and found the relative number of antagonists to correlate with the bacterial load and carbon-to-nitrogen (C/N) ratio of the soil. Consecutive studies show the importance of antagonist interactions between soil isolates and the lack of a predicted role for nutrient availability and, therefore, support an in situ role in offense for the production of toxins in environments of high bacterial loads. In addition, the production of extracellular DNAses (exDNases) and the ability to antagonize correlate strongly. Using an in domum-developed probabilistic cellular automaton model, we studied the consequences of exDNase production for both coexistence and diversity within a dynamic equilibrium. Our model demonstrates that exDNase-producing isolates involved in amensal interactions act to stabilize a community, leading to increased coexistence within a competitor-sensing interference competition environment. Our results signify that the environmental and biological cues that control natural-product formation are important for understanding antagonism and community dynamics, structure, and function, permitting the development of directed searches and the use of these insights for drug discovery. IMPORTANCE Ever since the first observation of antagonism by microorganisms by Ernest Duchesne (E. Duchesne, Contribution à l'étude de la concurrence vitale chez les microorganisms. Antagonism entre les moisissures et les microbes, These pour obtenir le grade de docteur en medicine, Lyon, France, 1897), many scientists successfully identified and applied bacteriogenic bioactive compounds from soils to cure infection. Unfortunately, overuse of antibiotics and the emergence of clinical antibiotic resistance, combined with a lack of discovery, have hampered our ability to combat infections. A deeper understanding of the biology of toxins and the cues leading to their production may elevate the success rate of the much-needed discovery of novel antibiotics. We initiated this line of research and discovered that bacterial reciprocal antagonism is associated with exDNase production in isolates from environments with high bacterial loads, while diversity may increase in environments of lower bacterial loads.

Phyllotaxis as geometric canalization during plant development.

Why living forms develop in a relatively robust manner, despite various sources of internal or external variability, is a fundamental question in developmental biology. Part of the answer relies on the notion of developmental constraints: at any stage of ontogenesis, morphogenetic processes are constrained to operate within the context of the current organism being built. One such universal constraint is the shape of the organism itself, which progressively channels the development of the organism toward its final shape. Here, we illustrate this notion with plants, where strikingly symmetric patterns (phyllotaxis) are formed by lateral organs. This Hypothesis article aims first to provide an accessible overview of phyllotaxis, and second to argue that the spiral patterns in plants are progressively canalized from local interactions of nascent organs. The relative uniformity of the organogenesis process across all plants then explains the prevalence of certain patterns in plants, i.e. Fibonacci phyllotaxis.

Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube.

Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl-L-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226× delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of compensatory regulation may exist to maintain overall proportions in the neural tube. We propose a model in which Kif11 normally functions during mitotic spindle formation to facilitate the progression of radial glia through mitosis, which leads to the maturation of progeny into specific secondary neuronal and glial lineages in the developing neural tube.