Characteristics and Outcomes of De Novo Genitourinary Malignancy in Solid Organ Transplant Recipients at the University of Minnesota.

BACKGROUND: Studies examining outcomes of genitourinary malignancy (GU) in the solid organ transplant (SOT) population predominantly focus on renal transplant recipients and consist of relatively small cohorts. We aimed to expand knowledge of the characteristics and outcomes of de novo GU malignancies in all patients with SOT at a large tertiary center. METHODS: The SOT database was queried for recipients with de novo bladder, renal cell, and prostate malignancy, and a retrospective chart review was performed. Descriptive statistics and Kaplan-Meier survival estimates were calculated. Cox proportional hazards regression was used for multivariate modeling of predictive factors in the development of GU malignancy. RESULTS: Solid organ transplant recipients with de novo bladder malignancy comprised 64.3% with high grade and 38.1% with advanced stage (≥T2) disease at initial diagnosis. Only 3.7% of patients with de novo renal cell carcinoma presented with metastatic disease, and 13.6% with localized disease developed recurrences. The most common stage in de novo prostate cancer patients was pT3 (52.2%). Kaplan-Meier estimates (95% CI) for 5-year overall (OS) and cancer-specific survival (CSS) were 44.12% (31.13-62.52) and 80.80% (68.85-94.81) for bladder, 78.90% (68.93-90.30) and 96.61% (92.10-100.00) for renal cell, and 81.18% (72.01-91.51) and 96.16% (90.95-100.00) for prostate cancer, respectively. Age at transplant and time from transplant to cancer diagnosis were predictive of de novo bladder cancer OS (P = .042 and .021, respectively). CONCLUSION: To our knowledge, this is the largest single-center cohort examined for GU malignancy after SOT. Bladder and renal cell cancer had worse OS but similar CSS as historical rates for nontransplant patients. De novo prostate cancer had similar CSS.

The Oligosaccharyltransferase AglB Supports Surface-Associated Growth and Iron Oxidation in Methanococcus maripaludis.

Most microbial organisms grow as surface-attached communities known as biofilms. However, the mechanisms whereby methanogenic archaea grow attached to surfaces have remained understudied. Here, we show that the oligosaccharyltransferase AglB is essential for growth of Methanococcus maripaludis strain JJ on glass or metal surfaces. AglB glycosylates several cellular structures, such as pili, archaella, and the cell surface layer (S-layer). We show that the S-layer of strain JJ, but not strain S2, is a glycoprotein, that only strain JJ was capable of growth on surfaces, and that deletion of aglB blocked S-layer glycosylation and abolished surface-associated growth. A strain JJ mutant lacking structural components of the type IV-like pilus did not have a growth defect under any conditions tested, while a mutant lacking the preflagellin peptidase (ΔflaK) was defective for surface growth only when formate was provided as the sole electron donor. Finally, for strains that are capable of Fe0 oxidation, we show that deletion of aglB decreases the rate of anaerobic Fe0 oxidation, presumably due to decreased association of biomass with the Fe0 surface. Together, these data provide an initial characterization of surface-associated growth in a member of the methanogenic archaea. IMPORTANCE Methanogenic archaea are responsible for producing the majority of methane on Earth and catalyze the terminal reactions in the degradation of organic matter in anoxic environments. Methanogens often grow as biofilms associated with surfaces or partner organisms; however, the molecular details of surface-associated growth remain uncharacterized. We have found evidence that glycosylation of the cell surface layer is essential for growth of M. maripaludis on surfaces and can enhance rates of anaerobic iron corrosion. These results provide insight into the physiology of surface-associated methanogenic organisms and highlight the importance of surface association for anaerobic iron corrosion.

Type IV-Like Pili Facilitate Transformation in Naturally Competent Archaea.

Naturally competent organisms are capable of DNA uptake directly from the environment through the process of transformation. Despite the importance of transformation to microbial evolution, DNA uptake remains poorly characterized outside of the bacterial domain. Here, we identify the pilus as a necessary component of the transformation machinery in archaea. We describe two naturally competent organisms, Methanococcus maripaludis and Methanoculleus thermophilus In M. maripaludis, replicative vectors were transferred with an average efficiency of 2.4 × 103 transformants µg-1 DNA. In M. thermophilus, integrative vectors were transferred with an average efficiency of 2.7 × 103 transformants µg-1 DNA. Additionally, natural transformation of M. thermophilus could be used to introduce chromosomal mutations. To our knowledge, this is the first demonstration of a method to introduce targeted mutations in a member of the order Methanomicrobiales For both organisms, mutants lacking structural components of the type IV-like pilus filament were defective for DNA uptake, demonstrating the importance of pili for natural transformation. Interestingly, competence could be induced in a noncompetent strain of M. maripaludis by expressing pilin genes from a replicative vector. These results expand the known natural competence pili to include examples from the archaeal domain and highlight the importance of pili for DNA uptake in diverse microbial organisms.IMPORTANCE Microbial organisms adapt and evolve by acquiring new genetic material through horizontal gene transfer. One way that this occurs is natural transformation, the direct uptake and genomic incorporation of environmental DNA by competent organisms. Archaea represent up to a third of the biodiversity on Earth, yet little is known about transformation in these organisms. Here, we provide the first characterization of a component of the archaeal DNA uptake machinery. We show that the type IV-like pilus is essential for natural transformation in two archaeal species. This suggests that pili are important for transformation across the tree of life and further expands our understanding of gene flow in archaea.