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Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), kills 1.6 million people annually. To bridge the gap between structure- and cell-based drug discovery strategies, we are pionee...

This study shows that Vochysia guatemalensis tree plantations were associated with enhanced soil biotic and abiotic characteristics in previously cleared forests in the northern zone of Costa Rica, suggesting the possible use of this practice as a restoration strategy for local land owners. Soil samples from a primary forest, secondary forest, and a 13‐year‐old plantation of V. guatemalensis had greater relative abundances of DNA sequences of microbial genera critical for carbon‐use (C‐use) efficiency (i.e. the saprobe, complex C and wood rot/lignin decomposer fungi, and bacterial lignin and other complex C degraders), and greater levels of total organic carbon, C‐biomass, and microbial quotients as indicators of enhanced C‐use efficiency, than found in soils of adjacent 5‐year‐old V. guatemalensis plantations and abandoned non‐productive pasture/grasslands (GRs). The major research conclusions were that (1) conversion of forested land into abandoned pasture/GRs decreased the C‐use efficiency in the soils and the microbial groups associated with C‐use efficiency; (2) soils in plantations of V. guatemalensis were associated with increased abundances of the DNA of these same microbial groups and enhanced C‐use efficiency; (3) DNA‐based taxonomic analysis of microbes and analysis of the microbial quotient values can be used to monitor soil ecosystems for assessment of the efficacy of restoration activities. Thus, planting V. guatemalensis on damaged lands in the Maquenque National Wildlife Refuge should be encouraged to provide a sustainable forestry crop that can be harvested rotationally, while improving soil ecosystem health and reducing the pressure to harvest other forest sites.

Inga edulis and Pentaclethra macroloba are dominant N-fixing forest trees in Costa Rica, likely important for recovery of soil N and C after deforestation, yet little is known of their soil microbiomes nor how land use impacts them. Soils from both trees in a primary and secondary forest were assessed for N-cycle metrics and DNA sequence-based composition of total bacterial, potential N-fixing bacterial, and potential ammonium oxidizing bacterial genera. The compositions of the functional groups of bacteria, but not their total relative abundance of DNA, were different across the soils. The P. macroloba soils had greater NO3&minus, levels and richness of both functional groups, while I. edulis soils had greater NH4+ levels, consistent with its NH4+ preference for root nodule development. The bacterial communities were different by habitat, as secondary forest I. edulis microbiomes were less rich, more dominant, possibly more affected by the disturbance, or reached equilibrium status quicker than the richer, less dominant P. macroloba microbiomes, which may be developing slower along with secondary forest succession, or were less affected by the disturbance. Functional redundancy and switching of 10 N-cycle bacterial genera was evident between the primary and secondary forest soils, likely to maintain stable levels of N-cycle activity following disturbance. In summary, the two tree soil microbiomes are different, land use differentially affects them, and, thus, both tree species should be used during forest regeneration strategies in this region.

Logging road development is considered as potentially more damaging to a tropical forest than the felling of the actual trees. However, little work has been conducted to determine how logging road development impacts the soil microbial communities and associated C and N cycle activities in tropical forests. This study was conducted within an upland tropical forest in the Northern Zone of Costa Rica that had a 2-year abandoned logging road system (used for harvesting trees felled during a tornado) to determine how development of logging roads affected soil C and N cycle activities, efficiency of organic C use, and bacterial and fungal community compositions. Soil samples from a set of logging roads, the road edges, and adjacent primary forests were analyzed for C, N metrics, the Microbial Quotients, and DNA-based microbial taxonomic community compositions; which were tested for differences using multivariate statistical analyses. The logging road soils had significantly greater bulk density and clay, and lower levels of sand, TN, NO3−, NO3−/NH4+, TOC, C Biomass, and Microbial Quotients compared to the road edge and forest soils. The composition of the total bacterial genera of the road edge and forest soils were similar to one another and different from that of the logging road soils, and the composition of the total fungal genera was unique within each of the three areas sampled. The relative abundance of DNA sequences of N-cycle bacteria were greater, and lignin degrading bacteria and wood rot/lignin degrading fungi were less in the logging roads compared to the edge and forest soils. These results suggest that the rate of recovery of both the C and N cycle activities and associated microbial groups in the soils from the road edges is occurring more rapidly than in the abandoned logging road soils. Thus, we suggest that a new tropical forest management practice should include the movement of the slash and debris from the road edge regions onto the logging roads after abandonment, as it would enhance the rate of recovery of both the C and N cycle activities in the soils, and perhaps begin to address the concern that logging roads add an additional 10–15 years to tropical forest recovery following deforestation.

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), kills 1.6 million people annually. To bridge the gap between structure- and cell-based drug discovery strategies, we are pioneering a computer-aided discovery paradigm that merges structure-based virtual screening with ligand-based, machine learning methods trained with cell-based data. This approach successfully identified N-(3-methoxyphenyl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (JSF-2164) as an inhibitor of purified InhA with whole-cell efficacy versus in vitro cultured M. tuberculosis. When the intrabacterial drug metabolism (IBDM) platform was leveraged, mechanistic studies demonstrated that JSF-2164 underwent a rapid F(420)H(2)-dependent biotransformation within M. tuberculosis to afford intrabacterial nitric oxide and two amines, identified as JSF-3616 and JSF-3617. Thus, metabolism of JSF-2164 obscured the InhA inhibition phenotype within cultured M. tuberculosis. This study demonstrates a new docking/Bayesian computational strategy to combine cell- and target-based drug screening and the need to probe intrabacterial metabolism when clarifying the antitubercular mechanism of action.