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Annual Review of Virology Sep 2023Host defense against viral pathogens is an essential function for all living organisms. In cell-intrinsic innate immunity, dedicated sensor proteins recognize molecular... (Review)
Review
Host defense against viral pathogens is an essential function for all living organisms. In cell-intrinsic innate immunity, dedicated sensor proteins recognize molecular signatures of infection and communicate to downstream adaptor or effector proteins to activate immune defense. Remarkably, recent evidence demonstrates that much of the core machinery of innate immunity is shared across eukaryotic and prokaryotic domains of life. Here, we review a pioneering example of evolutionary conservation in innate immunity: the animal cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) signaling pathway and its ancestor in bacteria, CBASS (cyclic nucleotide-based antiphage signaling system) antiphage defense. We discuss the unique mechanism by which animal cGLRs (cGAS-like receptors) and bacterial CD-NTases (cGAS/dinucleotide-cyclase in (DncV)-like nucleotidyltransferases) in these pathways link pathogen detection with immune activation using nucleotide second messenger signals. Comparing the biochemical, structural, and mechanistic details of cGAS-STING, cGLR signaling, and CBASS, we highlight emerging questions in the field and examine evolutionary pressures that may have shaped the origins of nucleotide second messenger signaling in antiviral defense.
PubMed: 37380187
DOI: 10.1146/annurev-virology-111821-115636 -
Cell Jun 2023Biofilm formation is generally recognized as a bacterial defense mechanism against environmental threats, including antibiotics, bacteriophages, and leukocytes of the...
Biofilm formation is generally recognized as a bacterial defense mechanism against environmental threats, including antibiotics, bacteriophages, and leukocytes of the human immune system. Here, we show that for the human pathogen Vibrio cholerae, biofilm formation is not only a protective trait but also an aggressive trait to collectively predate different immune cells. We find that V. cholerae forms biofilms on the eukaryotic cell surface using an extracellular matrix comprising primarily mannose-sensitive hemagglutinin pili, toxin-coregulated pili, and the secreted colonization factor TcpF, which differs from the matrix composition of biofilms on other surfaces. These biofilms encase immune cells and establish a high local concentration of a secreted hemolysin to kill the immune cells before the biofilms disperse in a c-di-GMP-dependent manner. Together, these results uncover how bacteria employ biofilm formation as a multicellular strategy to invert the typical relationship between human immune cells as the hunters and bacteria as the hunted.
Topics: Animals; Humans; Vibrio cholerae; Predatory Behavior; Biofilms; Fimbriae, Bacterial; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 37295405
DOI: 10.1016/j.cell.2023.05.008 -
Applied and Environmental Microbiology Jun 2023Incidence of vibriosis is rising globally, with evidence that changing climatic conditions are influencing environmental factors that enhance growth of pathogenic spp....
Incidence of vibriosis is rising globally, with evidence that changing climatic conditions are influencing environmental factors that enhance growth of pathogenic spp. in aquatic ecosystems. To determine the impact of environmental factors on occurrence of pathogenic spp., samples were collected in the Chesapeake Bay, Maryland, during 2009 to 2012 and 2019 to 2022. Genetic markers for Vibrio vulnificus () and Vibrio parahaemolyticus (, , and ) were enumerated by direct plating and DNA colony hybridization. Results confirmed seasonality and environmental parameters as predictors. Water temperature showed a linear correlation with and , and two critical thresholds were observed, an initial increase in detectable numbers (>15°C) and a second increase when maximum counts were recorded (>25°C). Temperature and pathogenic V. parahaemolyticus ( and ) were not strongly correlated; however, the evidence showed that these organisms persist in oyster and sediment at colder temperatures. Salinity (10 to 15 ppt), total chlorophyll (5 to 25 μg/L), dissolved oxygen (5 to 10 mg/L), and pH (8) were associated with increased abundance of and . Importantly, a long-term increase in spp. numbers was observed in water samples between the two collection periods, specifically at Tangier Sound (lower bay), with the evidence suggesting an extended seasonality for these bacteria in the area. Notably, showed a mean positive increase that was ca. 3-fold overall, with the most significant increase observed during the fall. In conclusion, vibriosis continues to be a risk in the Chesapeake Bay region. A predictive intelligence system to assist decision makers, with respect to climate and human health, is warranted. The genus includes pathogenic species that are naturally occurring in marine and estuarine environments globally. Routine monitoring for species and environmental parameters influencing their incidence is critical to provide a warning system for the public when the risk of infection is high. In this study, occurrence of Vibrio parahaemolyticus and Vibrio vulnificus, both potential human pathogens, in Chesapeake Bay water, oysters, and sediment samples collected over a 13-year period was analyzed. The results provide a confirmation of environmental predictors for these bacteria, notably temperature, salinity, and total chlorophyll , and their seasonality of occurrence. New findings refine environmental parameter thresholds of culturable species and document a long-term increase in populations in the Chesapeake Bay. This study provides a valuable foundation for development of predicative risk intelligence models for incidence during climate change.
Topics: Animals; Humans; Vibrio parahaemolyticus; Vibrio vulnificus; Chlorophyll A; Ecosystem; Ostreidae; Vibrio Infections; Water
PubMed: 37222620
DOI: 10.1128/aem.00307-23 -
Current Opinion in Immunology Dec 2023Enterotoxin adjuvants have been researched for their ability to promote immunity to co-delivered antigens. Outside of cholera vaccines, however, these proteins have yet... (Review)
Review
Enterotoxin adjuvants have been researched for their ability to promote immunity to co-delivered antigens. Outside of cholera vaccines, however, these proteins have yet to be included in any currently licensed vaccines. They include molecules derived from the bacterial toxins of Vibrio cholerae, cholera toxin, or Escherichia coli, heat-labile toxin, such as detoxified mutants or subunits. This class of adjuvants is distinguished by their delivery possibilities, which include parenteral injection, skin applications, or direct mucosal administration by oral, sublingual, or nasal routes. In addition, inclusion of an enterotoxin adjuvant is associated with development of multifaceted cellular and humoral immune responses to vaccination. Here, we review exciting progress in the past few years in clinical trials for safety and efficacy, preclinical vaccines studies, and new mechanistic insights for enterotoxin adjuvants. This includes recent reports of their use in vaccines targeting microbial infections (bacterial, viral, parasitic) or substance abuse drugs.
Topics: Humans; Enterotoxins; Adjuvants, Vaccine; Cholera Toxin; Bacterial Toxins; Vaccines; Adjuvants, Immunologic; Escherichia coli
PubMed: 37976963
DOI: 10.1016/j.coi.2023.102398 -
Avicenna Journal of Medicine Oct 2023Cholera is an acute type of diarrheal disease caused by intestinal infection with the toxin-producing bacteria Vibrio cholerae. The disease is still endemic in almost 69... (Review)
Review
Cholera is an acute type of diarrheal disease caused by intestinal infection with the toxin-producing bacteria Vibrio cholerae. The disease is still endemic in almost 69 countries, accounting for around 2.86 million cases and 95,000 deaths annually. Cholera is associated with poor infrastructure, and lack of access to sanitation and clean drinking water. The current cholera outbreak in Syria is associated with more than 10 years of conflict, which has devastated infrastructures and health services. There were 132,782 suspected cases reported between August 25, 2022 and May 20, 2023 in all 14 governorates, including 104 associated deaths. The recent earthquake in the region has complicated the situation, with an increase in cholera cases, and hindrance to a response to the disease. Climate change has driven a number of large cholera outbreaks around the world this year. The World Health Organization prequalifies three oral cholera vaccines. Cholera treatment mainly depends on rehydration, with the use of antibiotics in more severe infections. This review gives an overview of cholera bacteriology, pathogenesis, epidemiology, clinical manifestations, diagnosis, management, and prevention in light of global climate change and the ongoing outbreak in Syria, which poses a significant public health threat that requires urgent attention.
PubMed: 38144913
DOI: 10.1055/s-0043-1775762 -
Proceedings of the National Academy of... Oct 2023Polymicrobial infections threaten the health of humans and animals but remain understudied in natural systems. We recently described the Pacific Oyster Mortality...
Polymicrobial infections threaten the health of humans and animals but remain understudied in natural systems. We recently described the Pacific Oyster Mortality Syndrome (POMS), a polymicrobial disease affecting oyster production worldwide. In the French Atlantic coast, the disease involves coinfection with ostreid herpesvirus 1 (OsHV-1) and virulent . However, it is unknown whether consistent populations are associated with POMS in different regions, how contribute to POMS, and how they interact with OsHV-1 during pathogenesis. By connecting field-based approaches in a Mediterranean ecosystem, laboratory infection assays and functional genomics, we uncovered a web of interdependencies that shape the structure and function of the POMS pathobiota. We show that and are predominant in OsHV-1-diseased oysters and that OsHV-1 drives the partition of the community observed in the field. However only synergizes with OsHV-1 by promoting mutual growth and accelerating oyster death. shows high-virulence potential and dampens oyster cellular defenses through a type 3 secretion system, making oysters a more favorable niche for microbe colonization. In addition, produces a key siderophore called vibrioferrin. This important resource promotes the growth of , which cooccurs with in diseased oysters, and behaves as a cheater by benefiting from metabolite sharing. Our data show that cooperative behaviors contribute to synergy between bacterial and viral coinfecting partners. Additional cheating behaviors further shape the polymicrobial consortium. Controlling cooperative behaviors or countering their effects opens avenues for mitigating polymicrobial diseases.
Topics: Animals; Humans; Ecosystem; Biological Assay; Coinfection; Cooperative Behavior; Ostreidae
PubMed: 37751557
DOI: 10.1073/pnas.2305195120