A New Pillar in Pilus Assembly.

Pilus assembly in bacteria typically occurs by one of four pathways. In the study by Xu et al., the structures of 20 pilin subunits of human oral and gut Bacteroidales are elucidated, revealing a new pilin superfamily, assembled into pili by a distinct fifth pathway.

Genome-wide chromatin state transitions associated with developmental and environmental cues.

Differences in chromatin organization are key to the multiplicity of cell states that arise from a single genetic background, yet the landscapes of in vivo tissues remain largely uncharted. Here, we mapped chromatin genome-wide in a large and diverse collection of human tissues and stem cells. The maps yield unprecedented annotations of functional genomic elements and their regulation across developmental stages, lineages, and cellular environments. They also reveal global features of the epigenome, related to nuclear architecture, that also vary across cellular phenotypes. Specifically, developmental specification is accompanied by progressive chromatin restriction as the default state transitions from dynamic remodeling to generalized compaction. Exposure to serum in vitro triggers a distinct transition that involves de novo establishment of domains with features of constitutive heterochromatin. We describe how these global chromatin state transitions relate to chromosome and nuclear architecture, and discuss their implications for lineage fidelity, cellular senescence, and reprogramming.

Transcriptional and epigenetic dynamics during specification of human embryonic stem cells.

Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of hESCs representing each of the three embryonic germ layers. Integration of whole-genome bisulfite sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing reveals unique events associated with specification toward each lineage. Lineage-specific dynamic alterations in DNA methylation and H3K4me1 are evident at putative distal regulatory elements that are frequently bound by pluripotency factors in the undifferentiated hESCs. In addition, we identified germ-layer-specific H3K27me3 enrichment at sites exhibiting high DNA methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches, leading to more faithful differentiation strategies as well as providing insights into the rewiring of human regulatory programs during cellular transitions.

Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells.

Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs colocalize in characteristic patterns at distinct chromatin environments, at genes of coherent functions, and at distal regulatory elements. When comparing between cell types, CRs redistribute to different loci but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function.

A general O-glycosylation system important to the physiology of a major human intestinal symbiont.

The Bacteroides are a numerically dominant genus of the human intestinal microbiota. These organisms harbor a rare bacterial pathway for incorporation of exogenous fucose into capsular polysaccharides and glycoproteins. The infrequency of glycoprotein synthesis by bacteria prompted a more detailed analysis of this process. Here, we demonstrate that Bacteroides fragilis has a general O-glycosylation system. The proteins targeted for glycosylation include those predicted to be involved in protein folding, protein-protein interactions, peptide degradation as well as surface lipoproteins. Protein glycosylation is central to the physiology of B. fragilis and is necessary for the organism to competitively colonize the mammalian intestine. We provide evidence that general O-glycosylation systems are conserved among intestinal Bacteroides species and likely contribute to the predominance of Bacteroides in the human intestine.

Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering.

The human gut microbiota is a dense microbial ecosystem with extensive opportunities for bacterial contact-dependent processes such as conjugation and Type VI secretion system (T6SS)-dependent antagonism. In the gut Bacteroidales, two distinct genetic architectures of T6SS loci, GA1 and GA2, are contained on Integrative and Conjugative Elements (ICE). Despite intense interest in the T6SSs of the gut Bacteroidales, there is only a superficial understanding of their evolutionary patterns, and of their dissemination among Bacteroidales species in human gut communities. Here, we combine extensive genomic and metagenomic analyses to better understand their ecological and evolutionary dynamics. We identify new genetic subtypes, document extensive intrapersonal transfer of these ICE to Bacteroidales species within human gut microbiomes, and most importantly, reveal frequent population fixation of these newly armed strains in multiple species within a person. We further show the distribution of each of the distinct T6SSs in human populations and show there is geographical clustering. We reveal that the GA1 T6SS ICE integrates at a minimal recombination site leading to their integration throughout genomes and their frequent interruption of genes, whereas the GA2 T6SS ICE integrate at one of three different tRNA genes. The exclusion of concurrent GA1 and GA2 T6SSs in individual strains is associated with intact T6SS loci and with an ICE-encoded gene. By performing a comprehensive analysis of mobile genetic elements (MGE) in co-resident Bacteroidales species in numerous human gut communities, we identify 74 MGE that transferred to multiple Bacteroidales species within individual gut microbiomes. We further show that only three other MGE demonstrate multi-species spread in human gut microbiomes to the degree demonstrated by the GA1 and GA2 ICE. These data underscore the ubiquity and dissemination of mobile T6SS loci within Bacteroidales communities and across human populations.

Nanaerobic growth enables direct visualization of dynamic cellular processes in human gut symbionts.

Mechanistic studies of anaerobic gut bacteria have been hindered by the lack of a fluorescent protein system to track and visualize proteins and dynamic cellular processes in actively growing bacteria. Although underappreciated, many gut "anaerobes" are able to respire using oxygen as the terminal electron acceptor. The oxygen continually released from gut epithelial cells creates an oxygen gradient from the mucus layer to the anaerobic lumen [L. Albenberg et al., Gastroenterology 147, 1055-1063.e8 (2014)], with oxygen available to bacteria growing at the mucus layer. Here, we show that Bacteroides species are metabolically and energetically robust and do not mount stress responses in the presence of 0.10 to 0.14% oxygen, defined as nanaerobic conditions [A. D. Baughn, M. H. Malamy, Nature 427, 441-444 (2004)]. Taking advantage of this metabolic capability, we show that nanaerobic growth provides sufficient oxygen for the maturation of oxygen-requiring fluorescent proteins in Bacteroides species. Type strains of four different Bacteroides species show bright GFP fluorescence when grown nanaerobically versus anaerobically. We compared four different red fluorescent proteins and found that mKate2 yields the highest red fluorescence intensity in our assay. We show that GFP-tagged proteins can be localized in nanaerobically growing bacteria. In addition, we used time-lapse fluorescence microscopy to image dynamic type VI secretion system processes in metabolically active Bacteroides fragilis The ability to visualize fluorescently labeled Bacteroides and fluorescently linked proteins in actively growing nanaerobic gut symbionts ushers in an age of imaging analyses not previously possible in these bacteria.

British Columbia Dentists' Perceptions and Practices Regarding HPV Vaccinations: A Cross-sectional Study.

INTRODUCTION: Human papillomavirus (HPV), as the most common form of sexually transmitted infection, has been implicated in almost one-third of oropharyngeal cancers. One way to prevent HPV infections is through vaccination. This study aimed to investigate whether dentists in British Columbia (BC) were willing to discuss, refer and administer the vaccine in a dental practice setting. METHODS: Our cross-sectional study used a survey consisting of 14 questions pertaining to demographics, scope of practice, barriers to discussing the HPV vaccine and willingness to engage in HPV vaccination. On 1 April 2021, the survey was distributed to all practising dentists in BC via a URL link; the link remained active for 30 days. Descriptive and inferential statistics were used to analyze results, and statistical significance was set at p < 0.05. RESULTS: Of the 201 respondent who completed a survey, 168 (84%) agreed that discussing the link between HPV and oropharyngeal cancer falls within their scope of practice. Fewer agreed that recommending (74%) and administering (39%) the HPV vaccine were within their scope of practice. Barriers that may contribute to this unwillingness included lack of professional policies and guidelines. Although a significant proportion of respondents were willing to educate patients on HPV, they were unwilling to discuss sexual history in a dental setting (p = 0.02). CONCLUSIONS: Despite a willingness to discuss and refer patients for HPV vaccination, most respondents were unwilling to administer the vaccine in a dental setting, as they perceived the act to fall outside their scope of practice. There remains a reluctance to engage in vaccination activities in dental settings in BC.

Analysis of Effector and Immunity Proteins of the GA2 Type VI Secretion Systems of Gut Bacteroidales.

Three distinct genetic architectures (GAs) of Type VI secretion systems (T6SSs) have been described in gut Bacteroidales species, each with unique genes and characteristics. Unlike the GA3 T6SSs, potent antagonism has not yet been demonstrated for the GA1 or GA2 T6SSs. We previously showed that the GA2 T6SS loci are contained on integrative and conjugative elements and that there are five subtypes. Collectively, GA2 are the most prevalent Bacteroidales T6SSs in the human populations analyzed. In this study, we provide a comprehensive bioinformatic analysis of the three variable regions of GA2 T6SS loci, which encode toxic effector and immunity proteins. In total, we identified 63 distinct effectors encoded within 31 nonredundant GA2 loci, 18 of which do not have described motifs or predicted functions. We provide experimental evidence for toxin activity for four different GA2 effectors, showing that each functions only when present in the periplasm, and experimentally confirm their cognate immunity proteins. Our data demonstrate that each GA2 locus encodes at least three distinct effectors with targets in both the cytoplasm and the periplasm. The data also suggest that the effectors of a given locus are loaded onto the tube by different mechanisms, which may allow all three effectors encoded within a single GA2 locus with distinct antibacterial activity to be loaded onto a single T6 tube, increasing the antagonistic effect. IMPORTANCE Humans are colonized with many gut Bacteroidales species at high density, allowing for extensive opportunities for contact-dependent antagonism. To begin to understand the antagonistic potential of the GA2 T6SSs of the gut Bacteroidales, we performed bioinformatic and experimental analyses of the three divergent regions containing the toxin effector and immunity genes. We show that each GA2 T6SS locus encodes at least three distinct toxic effectors including toxins linked to Rhs and Hcp with cytoplasmic targets, and unlinked effectors with targets in the periplasm. The diversity and modality of effectors exceeds that of the GA1 or GA3 T6SS loci (M. J. Coyne, K. G. Roelofs, and L. E. Comstock, BMC Genomics 17:58, 2016, https://doi.org/10.1186/s12864-016-2377-z) and suggests that these T6SSs have the potential to be potent antibacterial weapons in the human gut.

Analysis of a phase-variable restriction modification system of the human gut symbiont Bacteroides fragilis.

The genomes of gut Bacteroidales contain numerous invertible regions, many of which contain promoters that dictate phase-variable synthesis of surface molecules such as polysaccharides, fimbriae, and outer surface proteins. Here, we characterize a different type of phase-variable system of Bacteroides fragilis, a Type I restriction modification system (R-M). We show that reversible DNA inversions within this R-M locus leads to the generation of eight specificity proteins with distinct recognition sites. In vitro grown bacteria have a different proportion of specificity gene combinations at the expression locus than bacteria isolated from the mammalian gut. By creating mutants, each able to produce only one specificity protein from this region, we identified the R-M recognition sites of four of these S-proteins using SMRT sequencing. Transcriptome analysis revealed that the locked specificity mutants, whether grown in vitro or isolated from the mammalian gut, have distinct transcriptional profiles, likely creating different phenotypes, one of which was confirmed. Genomic analyses of diverse strains of Bacteroidetes from both host-associated and environmental sources reveal the ubiquity of phase-variable R-M systems in this phylum.

METHOD COMPARISON FOR MEASUREMENT OF SYMMETRIC DIMETHYLARGININE IN TIGERS (PANTHERA TIGRIS).

Renal disease is well documented in nondomestic felids and is monitored and diagnosed by serum concentration of blood urea nitrogen, creatinine, and phosphorous. Symmetric dimethylarginine (SDMA) has proven to be an earlier and more sensitive biomarker for the assessment of glomerular filtration rate. Although SDMA is commonly measured in nondomestic felids, information concerning the validity of the assay is lacking. The purpose of the study was to perform a method comparison between high-throughput immunoassay and the reference method, liquid chromatography-tandem mass spectrometry (LC-MS/MS), to quantify SDMA concentrations in tiger blood samples. Concentrations of SDMA were measured for 81 individual tiger samples. The SDMA immunoassay demonstrated excellent correlation to the LC-MS/MS reference method. A Passing and Bablok linear regression analysis had a slope of 1.03 (95% CI, 0.99-1.11), an intercept of 1.64 (95% CI, 0.46-2.34), and a Pearson R= 0.99. The mean bias was 1.53 µg/dl (95% CI, 0.63-2.42 µg/dl), and the limit of agreement was ±7.96 µg/dl. The degree of bias is within established acceptance criteria of 1-3 µg/dl for the immunoassay. Although this study provides good evidence of the utility of the immunoassay to measure SDMA in tiger serum and plasma, further assay validation is recommended.

The experience of point-of-care testing for influenza in Scotland in 2017/18 and 2018/19 - no gain without pain.

BackgroundDuring the 2017/18 and 2018/19 influenza seasons, molecular amplification-based point-of-care tests (mPOCT) were introduced in Scotland to aid triaging respiratory patients for hospital admission, yet communication of results to national surveillance was unaccounted for.AimThis retrospective study aims to describe steps taken to capture mPOCT data and assess impact on influenza surveillance.MethodsQuestionnaires determined mPOCT usage in 2017/18 and 2018/19. Searches of the Electronic Communication of Surveillance in Scotland (ECOSS) database were performed and compared with information stored in laboratory information management systems. Effect of incomplete data on surveillance was determined by comparing routine against enhanced data and assessing changes in influenza activity levels determined by the moving epidemic method.ResultsThe number of areas employing mPOCT increased over the two seasons (6/14 in 2017/18 and 8/14 in 2018/19). Analysis of a small number of areas (n = 3) showed capture of positive mPOCT results in ECOSS improved between seasons and remained high (> 94%). However, capture of negative results was incomplete. Despite small discrepancies in weekly activity assessments, routine data were able to identify trend, start, peak and end of both influenza seasons.ConclusionThis study has shown an improvement in capture of data from influenza mPOCT and has highlighted issues that need to be addressed for results to be accurately captured in national surveillance. With the clear benefit to patient management we suggest careful consideration should be given to the connectivity aspects of the technology in order to ensure minimal impact on national surveillance.

Association Between Exposure to Ehrlichia spp. and Risk of Developing Chronic Kidney Disease in Dogs.

Ehrlichiosis is a common vector-borne disease caused by Ehrlichia spp. This retrospective matched cohort study was performed to determine if dogs with Ehrlichia spp. antibodies had an increased incidence of chronic kidney disease (CKD). Exposure to Ehrlichia spp. was defined as having an Ehrlichia spp. antibody-positive result recorded at any point in their available patient history. The outcome of CKD was defined as concurrent increased symmetric dimethylarginine (>14 µg/dL) and creatinine (>1.5 mg/dL) for a minimum of 25 days with inappropriate urine specific gravity (<1.030). Patients were matched using propensity score matching to control for age, geography, and breed. A total of 22,440 patients and controls in E canis-endemic regions of the United States were used in this analysis. Contingency tables were used to compare dogs with and without exposure to Ehrlichia spp.-infected ticks and CKD outcome. The relative risk of CKD for patients exposed to ticks carrying Ehrlichia spp. was found to be 2.12 (95% confidence interval [1.35-3.15], p < 0.0006). This study identified that testing positive for Ehrlichia spp. antibodies in E canis-endemic regions is associated with higher incidence of CKD in dogs.

Identification of a Fifth Antibacterial Toxin Produced by a Single Bacteroides fragilis Strain.

Bacteroidales are the most abundant Gram-negative bacteria of the healthy human colonic microbiota, comprising nearly 50% of the colonic bacteria in many individuals. Numerous species and strains of gut Bacteroidales are present simultaneously at high concentrations in this ecosystem. Studies are revealing that gut Bacteroides has numerous antibacterial weapons to antagonize closely related members. In this study, we identify a new diffusible antibacterial toxin produced by Bacteroides fragilis 638R, designated BSAP-4. This is the fifth antibacterial toxin produced by this strain and the second toxin of this strain with a membrane attack complex/perforin domain (MACPF). We identify the target molecule of sensitive cells as a ß-barrel outer membrane protein (OMP) with calycin-like domains. As with other MACPF toxins, the gene encoding the target in sensitive strains is in the same genetic region as bsap-4 in producing strains. A comparison of B. fragilis strains showed there are two sensitive variants of this OMP that are 87% similar to each other and 50% similar to the resistant OMP. Unlike other MACPF toxins, there are numerous B. fragilis strains that harbor the resistant OMP without bsap-4 Several OMP variants from strains that are BSAP-4 resistant under the conditions of our assay confer BSAP-4 sensitivity to Bacteroides thetaiotaomicron when constitutively expressed. Using a reporter assay, we show that the BSAP-4 receptor gene is differentially expressed in sensitive and resistant strains leading to apparent BSAP-4 resistance under the conditions of our assay, despite harboring the BSAP-4 target gene.IMPORTANCE The intestinal microbiota is a diverse microbial ecosystem that provides numerous benefits to humans. The factors that govern its establishment and stability are just beginning to be elucidated. Identification and characterization of antimicrobial toxins produced by its members and their killing range are essential to understanding the role of antagonism in community composition and stability. Here, we identify a fifth antimicrobial toxin produced by a single Bacteroides fragilis strain and identify its target. The finding of such a large number of toxins that antagonize competing members suggests that this feature substantially contributes to the fitness of these bacteria. In addition, these toxins may have applications in genetically engineered gut bacteria to allow engraftment or to antagonize a potentially pathogenic member.

The importance of migratory connectivity for global ocean policy.

The distributions of migratory species in the ocean span local, national and international jurisdictions. Across these ecologically interconnected regions, migratory marine species interact with anthropogenic stressors throughout their lives. Migratory connectivity, the geographical linking of individuals and populations throughout their migratory cycles, influences how spatial and temporal dynamics of stressors affect migratory animals and scale up to influence population abundance, distribution and species persistence. Population declines of many migratory marine species have led to calls for connectivity knowledge, especially insights from animal tracking studies, to be more systematically and synthetically incorporated into decision-making. Inclusion of migratory connectivity in the design of conservation and management measures is critical to ensure they are appropriate for the level of risk associated with various degrees of connectivity. Three mechanisms exist to incorporate migratory connectivity into international marine policy which guides conservation implementation: site-selection criteria, network design criteria and policy recommendations. Here, we review the concept of migratory connectivity and its use in international policy, and describe the Migratory Connectivity in the Ocean system, a migratory connectivity evidence-base for the ocean. We propose that without such collaboration focused on migratory connectivity, efforts to effectively conserve these critical species across jurisdictions will have limited effect.

Schistosomiasis in Scottish travellers: public health importance of laboratory testing and the need for enhanced surveillance.

Background: Imported schistosomiasis is of significant public health importance and is likely to be underestimated since infection is often asymptomatic. We describe data from travellers residing in Scotland which includes a subset of group travellers from one of the largest Health Boards in Scotland. Methods: Clotted bloods were obtained during the period 2001-15 from a total of 8163 Scottish travellers. This included seven groups comprising of 182 travellers. Sera were examined for the presence of Schistosome species antibody at the Scottish Parasite Diagnostic and Reference Laboratory (SPDRL). Results: Of all, 25% (n = 1623) tested positive with 40% (n = 651) of those patients aged between 20 and 24 years. Although 62% (n = 1006) of those who tested positive reported travel to Africa, important information on the specific region visited was lacking in almost one-third of samples received. Overall, 62 (34%) of group travellers tested positive and 95% (n = 59) reporting travel to Africa. Conclusions: Globalization, affordable air travel and improved awareness, are likely to contribute towards the increasing number of imported schistosomiasis cases. Therefore, enhanced surveillance capturing detailed travel history and fresh water exposures will improve risk stratification, pre-travel advice and optimize testing and treatment regimes for this increasingly important parasitic disease.

Mapping and analysis of chromatin state dynamics in nine human cell types.

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.

Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements.

BACKGROUND: Type VI secretion systems (T6SSs) are contact-dependent antagonistic systems employed by Gram negative bacteria to intoxicate other bacteria or eukaryotic cells. T6SSs were recently discovered in a few Bacteroidetes strains, thereby extending the presence of these systems beyond Proteobacteria. The present study was designed to analyze in a global nature the diversity, abundance, and properties of T6SSs in the Bacteroidales, the most predominant Gram negative bacterial order of the human gut. RESULTS: By performing extensive bioinformatics analyses and creating hidden Markov models for Bacteroidales Tss proteins, we identified 130 T6SS loci in 205 human gut Bacteroidales genomes. Of the 13 core T6SS proteins of Proteobacteria, human gut Bacteroidales T6SS loci encode orthologs of nine, and an additional five other core proteins not present in Proteobacterial T6SSs. The Bacteroidales T6SS loci segregate into three distinct genetic architectures with extensive DNA identity between loci of a given genetic architecture. We found that divergent DNA regions of a genetic architecture encode numerous types of effector and immunity proteins and likely include new classes of these proteins. TheT6SS loci of genetic architecture 1 are contained on highly similar integrative conjugative elements (ICEs), as are the T6SS loci of genetic architecture 2, whereas the T6SS loci of genetic architecture 3 are not and are confined to Bacteroides fragilis. Using collections of co-resident Bacteroidales strains from human subjects, we provide evidence for the transfer of genetic architecture 1 T6SS loci among co-resident Bacteroidales species in the human gut. However, we also found that established ecosystems can harbor strains with distinct T6SS of all genetic architectures. CONCLUSIONS: This is the first study to comprehensively analyze of the presence and diversity of T6SS loci within an order of bacteria and to analyze T6SSs of bacteria from a natural community. These studies demonstrate that more than half of our gut Bacteroidales, equivalent to about » of the bacteria of this ecosystem, encode T6SSs. The data reveal several novel properties of these systems and suggest that antagonism between or distributed defense among these abundant intestinal bacteria may be common in established human gut communities.

Delving Into the Details: Implementing Multitiered K-3 Reading Supports in High-Priority Schools.

Although there is widespread agreement about the practices associated with multitiered systems of support (MTSS) frameworks in beginning reading, we often underestimate the systems and infrastructure that schools need to implement and sustain these practices. The real work of developing these systems often happens in the detailed-oriented and often messy world of schedules, routines, meetings, and materials. The purpose of this article is to describe a K-3 reading initiative where school teams serving high percentages of students at risk for reading difficulties "delved into the details" to work to overcome the complexities inherent in implementing multitiered reading supports in high priority schools.

An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins.

Bacteroidales are the most abundant Gram-negative bacteria of the human intestinal microbiota comprising more than half of the bacteria in many individuals. Some of the factors that these bacteria use to establish and maintain themselves in this ecosystem are beginning to be identified. However, ecological competition, especially interference competition where one organism directly harms another, is largely unexplored. To begin to understand the relevance of this ecological principle as it applies to these abundant gut bacteria and factors that may promote such competition, we screened Bacteroides fragilis for the production of antimicrobial molecules. We found that the production of extracellularly secreted antimicrobial molecules is widespread in this species. The first identified molecule, described in this manuscript, contains a membrane attack complex/perforin (MACPF) domain present in host immune molecules that kill bacteria and virally infected cells by pore formation, and mutations affecting key residues of this domain abrogated its activity. This antimicrobial molecule, termed BSAP-1, is secreted from the cell in outer membrane vesicles and no additional proteins are required for its secretion, processing or immunity of the producing cell. This study provides the first insight into secreted molecules that promote competitive interference among Bacteroidales strains of the human gut.