Macrophages have long been considered to contribute to HIV infection of the CNS; however, a recent study has contradicted this early work and suggests that myeloid cells are not an in vivo source of virus production. Here, we addressed the role of macrophages in HIV infection by first analyzing monocytes isolated from viremic patients and patients undergoing antiretroviral treatment. We were unable to find viral DNA or viral outgrowth in monocytes isolated from peripheral blood. To determine whether tissue macrophages are productively infected, we used 3 different but complementary humanized mouse models. Two of these models (bone marrow/liver/thymus [BLT] mice and T cell-only mice [ToM]) have been previously described, and the third model was generated by reconstituting immunodeficient mice with human CD34+ hematopoietic stem cells that were devoid of human T cells (myeloid-only mice [MoM]) to specifically evaluate HIV replication in this population. Using MoM, we demonstrated that macrophages can sustain HIV replication in the absence of T cells; HIV-infected macrophages are distributed in various tissues including the brain; replication-competent virus can be rescued ex vivo from infected macrophages; and infected macrophages can establish de novo infection. Together, these results demonstrate that macrophages represent a genuine target for HIV infection in vivo that can sustain and transmit infection.
Bacteria integrate environmental signals to regulate gene expression and protein production to adapt to their surroundings. One such behavioral adaptation is the formation of a biofilm, which can promote adherence and colonization and provide protection against antimicrobials.
The NASA EXport Processes in the Ocean from RemoTe Sensing (EXPORTS) program was established to better quantify the pathways of the biological carbon pump in order to gain a more comprehensive understanding of global carbon export efficiency. The summer 2018 field campaign in the vicinity of Ocean Station Papa (Station P; 50°N, 145°W) in the Northeast Pacific Ocean yielded evidence of low phytoplankton biomass and primary productivity dominated by small cells (<5 µm) that are reliant on recycled nutrients. Using combined 13C/15N stable isotope incubations, we calculated an average depth-integrated dissolved inorganic carbon uptake (net primary production) rate of 23.1 mmol C m–2 d–1 throughout the euphotic zone with small cells contributing 88.9% of the total daily DIC uptake. Average depth-integrated NO3– uptake rates were 1.5 mmol N m–2 d–1 with small cells contributing 73.4% of the total daily NO3– uptake. Estimates of new and regenerated production fluctuated, with small cells continuing to dominate both forms of production. The daily mixed-layer f-ratio ranged from 0.17 to 0.38 for the whole community, consistent with previous studies, which indicates a predominance of regenerated production in this region, with small and large cells (≥5 μm) having average f-ratios of 0.28 and 0.82, respectively. Peak phytoplankton biomass, total primary productivity and new production occurred between Julian Days 238 and 242 of our observation period, driven primarily by an increase in carbon and nitrate assimilation rates without apparent substantial shifts in the phytoplankton size-class structure. Our findings demonstrate the importance of small cells in performing the majority of net primary production and new production and the modest productivity fluctuations that occur in this iron-limited region of the Northeast Pacific Ocean, driven by ephemeral increases in new production, which could have significant ramifications for carbon export over broad timescales.
The Roseobacter clade is a group of alphaproteobacteria that have diverse metabolic and regulatory capabilities. They are abundant in marine environments and have a substantial role in marine ecology and biogeochemistry. However, interactions between roseobacters and other bacterioplankton have not been extensively explored. In this study, we identify a killing mechanism in the model roseobacter Ruegeria pomeroyi DSS-3 by coculturing it with a group of phylogenetically diverse bacteria. The killing mechanism is diffusible and occurs when cells are grown both on surfaces and in suspension and is dependent on cell density. A screen of random transposon mutants revealed that the killing phenotype, as well as resistance to killing, require genes within an ∼8-kb putative gamma-butyrolactone synthesis gene cluster, which resembles similar pheromone-sensing systems in actinomycetes that regulate secondary metabolite production, including antimicrobials. Transcriptomics revealed the gene cluster is highly upregulated in wild-type DSS-3 compared to a nonkiller mutant when grown in liquid coculture with a roseobacter target. Our findings show that R. pomeroyi has the capability to eliminate closely and distantly related competitors, providing a mechanism to alter the community structure and function in its native habitats. IMPORTANCE Bacteria carry out critical ecological and biogeochemical processes and form the foundations of ecosystems. Identifying the factors that influence microbial community composition and the functional capabilities encoded within them is key to predicting how microbes impact an ecosystem. Because microorganisms must compete for limited space and nutrients to promote their own propagation, they have evolved diverse mechanisms to outcompete or kill competitors. However, the genes and regulatory strategies that promote such competitive abilities are largely underexplored, particularly in free-living marine bacteria. Here, genetics and omics techniques are used to investigate how a model marine bacterium is capable of quickly eliminating natural competitors in coculture. We determined that a previously uncharacterized horizontally acquired gene cluster is required for this bacterium to kill diverse competitors. This work represents an important step toward understanding the mechanisms bacterial populations can use to become dominant members in marine microbial communities.
The second field campaign of the NASA EXport Processes in the Ocean from RemoTe Sensing (EXPORTS) program was conducted in the late spring of 2021 within the vicinity of the Porcupine Abyssal Plain (49.0 degrees N, 16.5 degrees W) in the North Atlantic Ocean. Observations from EXPORTS support previous characterizations of this system as highly productive and organic matter rich, with the majority of primary production occurring in large cells (>5 microns) such as diatoms that are primarily utilizing nitrate. Rates of total euphotic zone depth-integrated net primary production ranged from 36.4 to 146.6 mmol C m-2 d-1, with an observational period average f-ratio of 0.74, indicating predominantly new production. Substantial variability in the contribution of small (<5 microns) and large cells occurred over the observation period, coinciding with the end of the annual spring phytoplankton bloom. Physical changes associated with storms appear to have impacted the integrated production rates substantially, enhancing rates by ~10%. These disturbances altered the balance between contributions of the different phytoplankton size fractions, thus highlighting the important role of mixed layer variability in nutrient entrainment into the upper water column and production dynamics. In diatoms, inputs of silicic acid related to deepening of the mixed layer increased silicic acid uptake rates yet concomitant increases in NPP in large cells was not observed. This campaign serves as the high productivity endmember within the EXPORTS program and as such, elucidates how nutrient concentrations and size class play key roles in both low and high productivity systems, but in differing ways.
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