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Purpose: The aims of this study were to evaluate and compare fibroblast activation protein (FAP) expression and localization in surgically resected cholangiocarcinoma (CCA), primary and metastatic hepatocellular carcinoma (HCC), hepatocellular adenoma (HCA), and focal nodular hyperplasia (FNH), and to identify any association between CCA clinical or pathologic features and FAP expression. Materials and methods: FAP immunostaining from surgically resected CCA (N = 58), primary intrahepatic and extrahepatic metastatic HCC (N = 148), HCA (N26), and FNH (N = 19) was scored (negative, weak positive, moderate positive or strong positive) from tissue microarrays. FAP expression was compared between groups. CCA FAP expression was compared to clinical and tumor pathology features. Results: Moderate-strong FAP expression in the tumor stroma was present in 93.1% of CCA, 60.7% of extrahepatic metastatic HCC, 29.6% of primary HCC, 21.1% of FNH, and 11.6% of HCA. Moderate-strong FAP expression in tumor stroma was significantly more prevalent in CCA than HCC (p < 0.001), metastatic HCC (p = 0.005), HCA (p < 0.001) and FNH (p < 0.001). FAP was expressed in the stroma of all but one CCA (1.7%), and FAP expression in CCA tumor stroma was not associated with any clinical or tumor pathology features (p > 0.05, all). Conclusion: FAP is expressed in the stroma of a high proportion (93%) of primary CCA independent of patient clinical or tumor pathology features. As such, these data provide the tissue basis for systematically evaluating FAP as a theranostic target across a broad range of CCA subtypes. [ABSTRACT FROM AUTHOR]

Ammonia-oxidizing archaea (AOA) are key players in the nitrogen cycle and among the most abundant microorganisms in the ocean, thriving even in oxygen-depleted ecosystems. AOA produce the greenhouse gas nitrous oxide (N2O) as a byproduct of ammonia oxidation. Additionally, the recent discovery of a nitric oxide dismutation pathway in the AOA isolate Nitrosopumilus maritimus points toward other N2O production and consumption pathways in AOA. AOA that perform NO dismutation when exposed to oxygen depletion, produce oxygen and dinitrogen as final products. Based on the transient accumulation of N2O coupled with oxygen accumulation, N2O has been proposed as an intermediate in this novel archaeal pathway. In this study, we spiked N2O to oxygen-depleted incubations with pure cultures of two marine AOA isolates that were performing NO dismutation. By using combinations of N compounds with different isotopic signatures (15NO2− pool +44N2O spike and 14NO2− pool +46N2O spike), we evaluated the N2O spike effects on the production of oxygen and the isotopic signature of N2 and N2O. The experiments confirmed that N2O is an intermediate in NO dismutation by AOA, distinguishing it from similar pathways in other microbial clades. Furthermore, we showed that AOA rapidly reduce high concentrations of spiked N2O to N2. These findings advance our understanding of microbial N2O production and consumption in oxygen-depleted settings and highlight AOA as potentially important key players in N2O turnover. [ABSTRACT FROM AUTHOR]

Ammonia-oxidizing archaea (AOA) are key players in the nitrogen cycle and among the most abundant microorganisms in the ocean, thriving even in oxygen-depleted ecosystems. AOA produce the greenhouse gas nitrous oxide (N2O) as a byproduct of ammonia oxidation. Additionally, the recent discovery of a nitric oxide dismutation pathway in the AOA isolate Nitrosopumilus maritimus points toward other N2O production and consumption pathways in AOA. AOA that perform NO dismutation when exposed to oxygen depletion, produce oxygen and dinitrogen as final products. Based on the transient accumulation of N2O coupled with oxygen accumulation, N2O has been proposed as an intermediate in this novel archaeal pathway. In this study, we spiked N2O to oxygen-depleted incubations with pure cultures of two marine AOA isolates that were performing NO dismutation. By using combinations of N compounds with different isotopic signatures (15NO2 - pool +44N2O spike and 14NO2 - pool +46N2O spike), we evaluated the N2O spike effects on the production of oxygen and the isotopic signature of N2 and N2O. The experiments confirmed that N2O is an intermediate in NO dismutation by AOA, distinguishing it from similar pathways in other microbial clades. Furthermore, we showed that AOA rapidly reduce high concentrations of spiked N2O to N2. These findings advance our understanding of microbial N2O production and consumption in oxygen-depleted settings and highlight AOA as potentially important key players in N2O turnover. [ABSTRACT FROM AUTHOR]

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is becoming more common in the Western world due to changes in diet-related microbial dysbiosis, genetics and lifestyle. Incidences of gut permeability can predate IBD and continued gut barrier disruptions increase the exposure of bacterial antigens to the immune system thereby perpetuating chronic inflammation. Currently, most of the approved IBD therapies target individual pro-inflammatory cytokines and pathways. However, they fail in approximately 50% of patients due to their inability to overcome the redundant pro inflammatory immune responses. There is increasing interest in the therapeutic potential of T regulatory cells (Tregs) in inflammatory conditions due to their widespread capability to dampen inflammation, promote tolerance of intestinal bacteria, facilitate healing of the mucosal barrier and ability to be engineered for more targeted therapy. Intestinal Treg populations are inherently shaped by dietary molecules and gut microbiota-derived metabolites. Thus, understanding how these molecules influence Treg-mediated preservation of the intestinal barrier will provide insights into immune tolerance-mediated mucosal homeostasis. This review comprehensively explores the interplay between diet, gut microbiota, and immune system in influencing the intestinal barrier function to attenuate the progression of colitis. [ABSTRACT FROM AUTHOR]

The generation of hydrogen and reduced carbon compounds during serpentinization provides sustained energy for microorganisms on Earth, and possibly on other extraterrestrial bodies (e.g., Mars, icy satellites). However, the geochemical conditions that arise from water-rock reaction also challenge the known limits of microbial physiology, such as hyperalkaline pH, limited electron acceptors and inorganic carbon. Because cell membranes act as a primary barrier between a cell and its environment, lipids are a vital component in microbial acclimation to challenging physicochemical conditions. To probe the diversity of cell membrane lipids produced in serpentinizing settings and identify membrane adaptations to this environment, we conducted the first comprehensive intact polar lipid (IPL) biomarker survey of microbial communities inhabiting the subsurface at a terrestrial site of serpentinization. We used an expansive, custom environmental lipid database that expands the application of targeted and untargeted lipodomics in the study of microbial and biogeochemical processes. IPLs extracted from serpentinite-hosted fluid communities were comprised of >90% isoprenoidal and non-isoprenoidal diether glycolipids likely produced by archaeal methanogens and sulfate-reducing bacteria. Phospholipids only constituted ~1% of the intact polar lipidome. In addition to abundant diether glycolipids, betaine and trimethylated-ornithine aminolipids and glycosphingolipids were also detected, indicating pervasive membrane modifications in response to phosphate limitation. The carbon oxidation state of IPL backbones was positively correlated with the reduction potential of fluids, which may signify an energy conservation strategy for lipid synthesis. Together, these data suggest microorganisms inhabiting serpentinites possess a unique combination of membrane adaptations that allow for their survival in polyextreme environments. The persistence of IPLs in fluids beyond the presence of their source organisms, as indicated by 16S rRNA genes and transcripts, is promising for the detection of extinct life in serpentinizing settings through lipid biomarker signatures. These data contribute new insights into the complexity of lipid structures generated in actively serpentinizing environments and provide valuable context to aid in the reconstruction of past microbial activity from fossil lipid records of terrestrial serpentinites and the search for biosignatures elsewhere in our solar system. [ABSTRACT FROM AUTHOR]

Nitrososphaeria in the phylum Crenarchaeota, is a widespread archaeal class in the oceanic realm, playing an important role in the marine carbon and nitrogen cycle. Nitrososphaeria-derived membrane lipids, i.e., isoprenoid glycerol dialkyl glycerol tetraethers (GDGTs), are commonly employed to reconstruct past water temperatures using the TetraEther indeX of 86 carbon atoms (TEX86). This index is of particular importance for the brackish Baltic Sea as to date it appears to be the only applicable organic temperature proxy. In this study, we investigated the distribution of intact and core GDGTs and their potential source organisms in the water column of three deep basins located in the central Baltic Sea to evaluate the application of TEX86. A lipidomic approach on suspended particulate matter was combined with the molecular techniques 16S rRNA gene amplicon sequencing and CARD-FISH. The archaeal community was dominated by Nitrosopumilus (~83-100% of the total archaeal sequences). As other detected taxa known to produce GDGTs each represented less than 2% of the total archaeal sequences, Nitrosopumilus is likely the most dominant GDGT producer in the central Baltic Sea. However, the occurrence of phosphohexose (PH), instead of hexose-phosphohexose (HPH) headgroups, suggested that Nitrosopumilus in the Baltic Sea may differ physiologically from representatives of marine settings and other marginal seas, such as the Black Sea. In the Baltic Sea, Nitrosopumilus is most abundant in the suboxic zone, where intact cells peak according to both CARD-FISH data and intact polar lipid concentrations. The presented data therefore suggest that TEX86 reflects subsurface rather than surface temperature in the central Baltic Sea. [ABSTRACT FROM AUTHOR]

The prevalence of Merkel cell polyomavirus(MCPyV) in Merkel cell carcinoma(MCC) and non-MCC skin lesions and its possible role in the etiology of other skin diseases remain controversial. To systematically assess the association between MCPyV infection and MCC, non-MCC skin lesions, and normal skin. For this systematic review and meta-analysis, a comprehensive search for eligible studies was conducted using Medline Ovid, Pubmed, Web of Science, and the Cochrane CENTRAL databases until August 2021; references were searched to identify additional studies. Observational studies that investigated the association between MCPyV infection and MCC, non-MCC skin lesions, and normal skin using polymerase chain reaction(PCR) as a detection method and provided sufficient data to calculate the prevalence of MCPyV positivity. A total of 50 articles were included in the study after exclusion criteria were applied. Two reviewers independently reviewed and assessed the eligibility of the studies, and all disagreements were resolved by consensus. To determine the association between MCPyV and MCC, overall odds ratio (OR) were calculated with 95% CI using a random-effects model. Single-arm meta-analyses were performed to examine the prevalence rate of MCPyV+ in MCC, non-MCC skin lesions, and normal skin. The primary analysis was the prevalence rate of MCPyV+ in MCC. Secondary outcomes included the prevalence rate of MCPyV+ in non-MCC skin lesions and normal skin. A total of 50 studies involving 5428 patients were reviewed based on our inclusion and exclusion criteria. Compared with the control group, MCPyV infection was significantly associated with MCC (OR = 3.51, 95% CI = 2.96 - 4.05). The global prevalence of MCPyV+ in MCC, melanoma, squamous cell carcinoma, basal cell carcinoma, Bowen's disease, actinic keratosis, keratoacanthoma, seborrheic keratosis, and normal skin was 80%, 4%, 15%, 15%, 21%, 6%, 20%, 10%, and 11%, respectively. The current results suggest that MCPyV infection is significantly associated with an increased risk of MCC. However, the low prevalence rate of MCPyV+ in non-MCC skin lesions does not exclude a pathogenic association of this virus with the development of non-MCC skin lesions. [ABSTRACT FROM AUTHOR]

Anaerobic ammonium oxidation (anammox) is an important process of the nitrogen cycle, and the anammox bacteria have been studied in a wide variety of environments. However, the distribution, diversity, and abundance of anammox bacteria in hot springs remain enigmatic. In this study, the anammox process was firstly investigated in hot springs of Conghua, China. Anammox-like bacterial sequences that closely affiliated to " Candidatus Brocadia," " Candidatus Kuenenia," " Candidatus Scalindua," " Candidatus Anammoxoglobus," and " Candidatus Jettenia" were detected. Several operational taxonomic units (OTUs) from this study shared low sequence identities to the 16S rRNA gene of the known anammox bacteria, suggesting that they might be representing putative novel anammox bacteria. A quantitative PCR analysis of anammox-specific 16S rRNA gene confirmed that the abundance of anammox bacteria ranged from 1.60 × 104 to 1.20 × 107 copies L–1. Nitrate was a key environmental factor defining the geographical distribution of the anammox bacterial community in the hot spring ecosystem. Dissolved inorganic carbon had a significant influence on anammox bacterial biodiversity. Our findings for the first time revealed that the diverse anammox bacteria, including putative novel anammox bacterial candidates, were present in Conghua hot spring, which extended the existence of anammox bacteria to the hot springs in China and expands our knowledge of the biogeography of anammox bacteria. This work filled up the research lacuna of anammox bacteria in Chinese hot spring habitat and would guide for enrichment strategies of anammox bacteria of Conghua hot springs. [ABSTRACT FROM AUTHOR]

Thaumarchaeota and Thermoplasmatota are the most abundant planktonic archaea in the sea. Thaumarchaeota contain tetraether lipids as their major membrane lipids, but the lipid composition of uncultured planktonic Thermoplasmatota representatives remains unknown. To address this knowledge gap, we quantified archaeal cells and ether lipids in open ocean depth profiles (0–200 m) of the North Pacific Subtropical Gyre. Planktonic archaeal community structure and ether lipid composition in the water column partitioned into two separate clusters: one above the deep chlorophyll maximum, the other within and below it. In surface waters, Thermoplasmatota densities ranged from 2.11 × 106 to 6.02 × 106 cells/L, while Thaumarchaeota were undetectable. As previously reported for Thaumarchaeota, potential homologs of archaeal tetraether ring synthases were present in planktonic Thermoplasmatota metagenomes. Despite the absence of Thaumarchaeota in surface waters, measurable amounts of intact polar ether lipids were found there. Based on cell abundance estimates, these surface water archaeal ether lipids contributed only 1.21 × 10–9 ng lipid/Thermoplasmatota cell, about three orders of magnitude less than that reported for Thaumarchaeota cells. While these data indicate that even if some tetraether and diether lipids may be derived from Thermoplasmatota, they would only comprise a small fraction of Thermoplasmatota total biomass. Therefore, while both MGI Thaumarchaeota and MGII/III Thermoplasmatota are potential biological sources of archaeal GDGTs, the Thaumarchaeota appear to be the major contributors of archaeal tetraether lipids in planktonic marine habitats. These results extend and confirm previous reports of planktonic archaeal lipid sources, and further emphasize the need for Thermoplasmatota cultivation, to better characterize the membrane lipid constituents of marine planktonic Thermoplasmatota, and more precisely define the sources and patterns of archaeal tetraether lipid distributions in marine plankton. [ABSTRACT FROM AUTHOR]

Structurally diverse, specialized lipids are crucial components of microbial membranes and other organelles and play essential roles in ecological functioning. The detection of such lipids in the environment can reveal not only the occurrence of specific microbes but also the physicochemical conditions to which they are adapted to. Traditionally, liquid chromatography coupled with mass spectrometry allowed for the detection of lipids based on chromatographic separation and individual peak identification, resulting in a limited data acquisition and targeting of certain lipid groups. Here, we explored a comprehensive profiling of microbial lipids throughout the water column of a marine euxinic basin (Black Sea) using ultra high-pressure liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). An information theory framework combined with molecular networking based on the similarity of the mass spectra of lipids enabled us to capture lipidomic diversity and specificity in the environment, identify novel lipids, differentiate microbial sources within a lipid group, and discover potential biomarkers for biogeochemical processes. The workflow presented here allows microbial ecologists and biogeochemists to process quickly and efficiently vast amounts of lipidome data to understand microbial lipids characteristics in ecosystems. [ABSTRACT FROM AUTHOR]

MALDI-TOF mass spectrometry has revolutionized clinical microbiology diagnostics by delivering accurate, fast, and reliable identification of microorganisms. It is conventionally based on the detection of intracellular molecules, mainly ribosomal proteins, for identification at the species-level and/or genus-level. Nevertheless, for some microorganisms (e.g., for mycobacteria) extensive protocols are necessary in order to extract intracellular proteins, and in some cases a protein-based approach cannot provide sufficient evidence to accurately identify the microorganisms within the same genus (e.g., Shigella sp. vs E. coli and the species of the M. tuberculosis complex). Consequently lipids, along with proteins are also molecules of interest. Lipids are ubiquitous, but their structural diversity delivers complementary information to the conventional protein-based clinical microbiology matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) based approaches currently used. Lipid modifications, such as the ones found on lipid A related to polymyxin resistance in Gram-negative pathogens (e.g., phosphoethanolamine and aminoarabinose), not only play a role in the detection of microorganisms by routine MALDI-TOF mass spectrometry but can also be used as a read-out of drug susceptibility. In this review, we will demonstrate that in combination with proteins, lipids are a game-changer in both the rapid detection of pathogens and the determination of their drug susceptibility using routine MALDI-TOF mass spectrometry systems. [ABSTRACT FROM AUTHOR]

Planktonic archaea include predominantly Marine Group I Thaumarchaeota (MG I) and Marine Group II Euryarchaeota (MG II), which play important roles in the oceanic carbon cycle. MG I produce specific lipids called isoprenoid glycerol dibiphytanyl glycerol tetraethers (GDGTs), which are being used in the sea surface temperature proxy named TEX86. Although MG II may be the most abundant planktonic archaeal group in surface water, their lipid composition remains poorly characterized because of the lack of cultured representatives. Circumstantial evidence from previous studies of marine suspended particulate matter suggests that MG II may produce both GDGTs and archaeol-based lipids. In this study, integration of the 16S rRNA gene quantification and sequencing and lipid analysis demonstrated that MG II contributed significantly to the pool of archaeal tetraether lipids in samples collected from MG II-dominated surface waters of the Northwestern Pacific Ocean (NWPO). The archaeal lipid composition in MG II-dominated NWPO waters differed significantly from that of known MG I cultures, containing relatively more 2G-OH-, 2G- and 1G- GDGTs, especially in their acyclic form. Lipid composition in NWPO waters was also markedly different from MG I-dominated surface water samples collected in the East China Sea. GDGTs from MG II-dominated samples seemed to respond to temperature similarly to GDGTs from the MG I-dominated samples, which calls for further study using pure cultures to determine the exact impact of MG II on GDGT-based proxies. [ABSTRACT FROM AUTHOR]

Archaea are ubiquitous in the modern ocean where they are involved in the carbon and nitrogen biogeochemical cycles. However, the majority of Archaea remain uncultured. Archaeal specific membrane intact polar lipids (IPLs) are biomarkers of the presence and abundance of living cells. They comprise archaeol and glycerol dibiphytanyl glycerol tetraethers (GDGTs) attached to various polar headgroups. However, little is known of the IPLs of uncultured marine Archaea, complicating their use as biomarkers. Here, we analyzed suspended particulate matter (SPM) obtained in high depth resolution from a coastal and open ocean site in the eastern tropical South Pacific (ETSP) oxygen deficient zone (ODZ) with the aim of determining possible biological sources of archaeal IPL by comparing their composition by Ultra High Pressure Liquid Chromatography coupled to high resolution mass spectrometry with the archaeal diversity by 16S rRNA gene amplicon sequencing and their abundance by quantitative PCR. Thaumarchaeotal Marine Group I (MGI) closely related to Ca. Nitrosopelagicus and Nitrosopumilus dominated the oxic surface and upper ODZ water together with Marine Euryarchaeota Group II (MGII). High relative abundance of hexose phosphohexose- (HPH) crenarchaeol, the specific biomarker for living Thaumarchaeota, and HPH-GDGT-0, dihexose- (DH) GDGT-3 and -4 were detected in these water masses. Within the ODZ, DPANN (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, and Nanohaloarchaea) of the Woesearchaeota DHVE-6 group and Marine Euryarchaeota Group III (MGIII) were present together with a higher proportion of archaeol-based IPLs, which were likely made by MGIII, since DPANN archaea are supposedly unable to synthesize their own IPLs and possibly have a symbiotic or parasitic partnership with MGIII. Finally, in deep suboxic/oxic waters a different MGI population occurred with HPH-GDGT-1, -2 and DH-GDGT-0 and -crenarchaeol, indicating that here MGI synthesize membranes with IPLs in a different relative abundance which could be attributed to the different detected population or to an environmental adaptation. Our study sheds light on the complex archaeal community of one of the most prominent ODZs and on the IPL biomarkers they potentially synthesize. [ABSTRACT FROM AUTHOR]

Microbial communities in marine oxygen deficient zones (ODZs) are responsible for up to half of marine N loss through conversion of nutrients to N2O and N2. This N loss is accomplished by a consortium of diverse microbes, many of which remain uncultured. Here, we characterize genes for all steps in the anoxic N cycle in metagenomes from the water column and >30 μm particles from the Eastern Tropical North Pacific (ETNP) ODZ. We use an approach that allows for both phylogenetic identification and semi-quantitative assessment of gene abundances from individual organisms, and place these results in context of chemical measurements and rate data from the same location. Denitrification genes were enriched in >30 μm particles, even in the oxycline, while anammox bacteria were not abundant on particles. Many steps in denitrification were encoded by multiple phylotypes with different distributions. Notably three N2O reductases (nosZ), each with no cultured relative, inhabited distinct niches; one was free-living, one dominant on particles and one had a C terminal extension found in autotrophic S-oxidizing bacteria. At some depths >30% of the community possessed nitrite reductase nirK. A nirK OTU linked to SAR11 explained much of this abundance. The only bacterial gene found for NO reduction to N2O in the ODZ was a form of qnorB related to the previously postulated "nitric oxide dismutase," hypothesized to produce N2 directly while oxidizing methane. However, similar qnorB-like genes are also found in the published genomes of many bacteria that do not oxidize methane, and here the qnorB-like genes did not correlate with the presence of methane oxidation genes. Correlations with N2O concentrations indicate that these qnorB-like genes likely facilitate NO reduction to N2O in the ODZ. In the oxycline, qnorB-like genes were not detected in the water column, and estimated N2O production rates from ammonia oxidation were insufficient to support the observed oxycline N2O maximum. However, both qnorB-like and nosZ genes were present within particles in the oxycline, suggesting a particulate source of N2O and N2. Together, our analyses provide a holistic view of the diverse players in the low oxygen nitrogen cycle. [ABSTRACT FROM AUTHOR]

Transformation and mobilization of bioessential elements in the biosphere, lithosphere, atmosphere, and hydrosphere constitute the Earth's biogeochemical cycles, which are driven mainly by microorganisms through their energy and material metabolic processes. Without microbial energy harvesting from sources of light and inorganic chemical bonds for autotrophic fixation of inorganic carbon, there would not be sustainable ecosystems in the vast ocean. Although ecological energetics (eco-energetics) has been emphasized as a core aspect of ecosystem analyses and microorganisms largely control the flow of matter and energy in marine ecosystems, marine microbial communities are rarely studied from the eco-energetic perspective. The diverse bioenergetic pathways and eco-energetic strategies of the microorganisms are essentially the outcome of biosphere-geosphere interactions over evolutionary times. The biogeochemical cycles are intimately interconnected with energy fluxes across the biosphere and the capacity of the ocean to fix inorganic carbon is generally constrained by the availability of nutrients and energy. The understanding of how microbial eco-energetic processes influence the structure and function of marine ecosystems and how they interact with the changing environment is thus fundamental to a mechanistic and predictive understanding of the marine carbon and nitrogen cycles and the trends in global change. By using major groups of chemolithoautotrophic microorganisms that participate in the marine nitrogen cycle as examples, this article examines their eco-energetic strategies, contributions to carbon cycling, and putative responses to and impacts on the various global change processes associated with global warming, ocean acidification, eutrophication, deoxygenation, and pollution. We conclude that knowledge gaps remain despite decades of tremendous research efforts. The advent of new techniques may bring the dawn to scientific breakthroughs that necessitate the multidisciplinary combination of eco-energetic, biogeochemical and "omics" studies in this field. [ABSTRACT FROM AUTHOR]

Denitrifying and anammox bacteria are involved in the nitrogen cycling in marine sediments but the environmental factors that regulate the relative importance of these processes are not well constrained. Here, we evaluated the abundance, diversity, and potential activity of denitrifying, anammox, and sulfide-dependent denitrifying bacteria in the sediments of the seasonally hypoxic saline Lake Grevelingen, known to harbor an active microbial community involved in sulfur oxidation pathways. Depth distributions of 16S rRNA gene, nirS gene of denitrifying and anammox bacteria, aprA gene of sulfur-oxidizing and sulfate-reducing bacteria, and ladderane lipids of anammox bacteria were studied in sediments impacted by seasonally hypoxic bottom waters. Samples were collected down to 5 cm depth (1 cm resolution) at three different locations before (March) and during summer hypoxia (August). The abundance of denitrifying bacteria did not vary despite of differences in oxygen and sulfide availability in the sediments, whereas anammox bacteria were more abundant in the summer hypoxia but in those sediments with lower sulfide concentrations. The potential activity of denitrifying and anammox bacteria as well as of sulfur-oxidizing, including sulfide-dependent denitrifiers and sulfate-reducing bacteria, was potentially inhibited by the competition for nitrate and nitrite with cable and/or Beggiatoa-like bacteria in March and by the accumulation of sulfide in the summer hypoxia. The simultaneous presence and activity of organoheterotrophic denitrifying bacteria, sulfide-dependent denitrifiers, and anammox bacteria suggests a tight network of bacteria coupling carbon-, nitrogen-, and sulfur cycling in Lake Grevelingen sediments. [ABSTRACT FROM AUTHOR]