-
FEMS Microbiology Letters Aug 2012Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis, an inflammatory disease that destroys the tissues... (Review)
Review
Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis, an inflammatory disease that destroys the tissues supporting the tooth, eventually leading to tooth loss. Porphyromonas gingivalis has can locally invade periodontal tissues and evade the host defence mechanisms. In doing so, it utilizes a panel of virulence factors that cause deregulation of the innate immune and inflammatory responses. The present review discusses the invasive and evasive strategies of P. gingivalis and the role of its major virulence factors in these, namely lipopolysaccharide, capsule, gingipains and fimbriae. Moreover, the role of P. gingivalis as a 'keystone' biofilm species in orchestrating a host response, is highlighted.
Topics: Adhesins, Bacterial; Animals; Bacterial Capsules; Cysteine Endopeptidases; Cytokines; Fimbriae, Bacterial; Gingipain Cysteine Endopeptidases; Humans; Immunity, Innate; Mouth; Periodontitis; Porphyromonas gingivalis; Virulence Factors
PubMed: 22530835
DOI: 10.1111/j.1574-6968.2012.02579.x -
MBio Jun 2020is one of the most abundant gut symbiont species, whose contribution to host health through its ability to degrade dietary polysaccharides and mature the immune system...
is one of the most abundant gut symbiont species, whose contribution to host health through its ability to degrade dietary polysaccharides and mature the immune system is under intense scrutiny. In contrast, adhesion and biofilm formation, which are potentially involved in gut colonization and microbiota structure and stability, have hardly been investigated in this intestinal bacterium. To uncover biofilm-related functions, we performed a transposon mutagenesis in the poorly biofilm-forming reference strain VPI-5482 and showed that capsule 4, one of the eight capsules, hinders biofilm formation. We then showed that the production of capsules 1, 2, 3, 5, and 6 also inhibits biofilm formation and that decreased capsulation of the population correlated with increased biofilm formation, suggesting that capsules could be masking adhesive surface structures. In contrast, we showed that capsule 8 displayed intrinsic adhesive properties. Finally, we demonstrated that , the homolog of the glycosylation locus, competes with capsule production and impacts its adhesion capacity. This study therefore establishes capsule regulation as a major determinant of biofilm formation, providing new insights into how modulation of different surface structures affects biofilm formation. The human gut harbors a complex bacterial community that plays important roles in host health and disease, including nutrient acquisition, maturation of the immune system, and resistance to infections. The capacity to adhere to surfaces and form communities called biofilms is believed to be important for niche colonization and maintenance of gut bacteria. However, little is known about the adhesion capacity of most gut bacteria. In this study, we investigated biofilm formation in , one of the most abundant bacteria of the normal mammalian intestine. We identified that capsules, a group of eight surface-exposed polysaccharidic layers mediating important interactions with the gut environment, are also major determinants of biofilm formation that mask or unmask adhesion factors. Studying how regulates its adhesion properties will allow us to better understand the physiology and specific properties of this important gut symbiont within anaerobic biofilms.
Topics: Animals; Bacterial Adhesion; Bacterial Capsules; Bacteroides thetaiotaomicron; Biofilms; Gene Expression Regulation, Bacterial; Male; Mice; Mice, Inbred C3H; Mutagenesis; Polysaccharides, Bacterial; Specific Pathogen-Free Organisms
PubMed: 32576670
DOI: 10.1128/mBio.00729-20 -
The Journal of Biological Chemistry Nov 2019The exopolysaccharide capsule of is an important virulence factor, but the mechanisms that regulate capsule thickness are not fully understood. Here, we investigated...
The exopolysaccharide capsule of is an important virulence factor, but the mechanisms that regulate capsule thickness are not fully understood. Here, we investigated the effects of various exogenously supplied carbohydrates on capsule production and gene expression in several pneumococcal serotypes. Microscopy analyses indicated a near absence of the capsular polysaccharide (CPS) when was grown on fructose. Moreover, serotype 7F pneumococci produced much less CPS than strains of other serotypes (6B, 6C, 9V, 15, and 23F) when grown on glucose or sucrose. RNA-sequencing revealed carbon source-dependent regulation of distinct genes of WT strains and capsule-switch mutants of serotypes 6B and 7F, but could not explain the mechanism of capsule thickness regulation. In contrast, P NMR of whole-cell extract from capsule-knockout strains (Δ) clearly revealed the accumulation or absence of capsule precursor metabolites when cells were grown on glucose or fructose, respectively. This finding suggests that fructose uptake mainly results in intracellular fructose 1-phosphate, which is not converted to CPS precursors. In addition, serotype 7F strains accumulated more precursors than did 6B strains, indicating less efficient conversion of precursor metabolites into the CPS in 7F, in line with its thinner capsule. Finally, isotopologue sucrose labeling and NMR analyses revealed that the uptake of the labeled fructose subunit into the capsule is <10% that of glucose. Our findings on the effects of carbon sources on CPS production in different serotypes may contribute to a better understanding of pneumococcal diseases and could inform future therapeutic approaches.
Topics: Bacterial Capsules; Carbon; Fructose; Gene Expression Regulation, Bacterial; Glucose; Humans; Pneumococcal Infections; Polysaccharides, Bacterial; Streptococcus pneumoniae; Sucrose
PubMed: 31594867
DOI: 10.1074/jbc.RA119.010764 -
International Journal of Molecular... Apr 2022In this study, several different depolymerases encoded in the prophage regions of genomes have been bioinformatically predicted and recombinantly produced. The...
In this study, several different depolymerases encoded in the prophage regions of genomes have been bioinformatically predicted and recombinantly produced. The identified depolymerases possessed multi-domain structures and were identical or closely homologous to various proteins encoded in other genomes. This means that prophage-derived depolymerases are widespread, and different bacterial genomes can be the source of proteins with polysaccharide-degrading activities. For two depolymerases, the specificity to capsular polysaccharides (CPSs) of belonging to K1 and K92 capsular types (K types) was determined. The data obtained showed that the prophage-derived depolymerases were glycosidases that cleaved the CPSs by the hydrolytic mechanism to yield monomers and oligomers of the K units. The recombinant proteins with established enzymatic activity significantly reduced the mortality of larvae infected with of K1 and K92 capsular types. Therefore, these enzymes can be considered as suitable candidates for the development of new antibacterials against corresponding K types.
Topics: Acinetobacter baumannii; Bacterial Capsules; Bacteriophages; Glycoside Hydrolases; Polysaccharides; Polysaccharides, Bacterial; Prophages
PubMed: 35563361
DOI: 10.3390/ijms23094971 -
PLoS Pathogens Nov 2022Streptococcus pyogenes is a globally prominent human-specific pathogen responsible for an enormous burden of human illnesses, including >600 million pharyngeal and >100...
Streptococcus pyogenes is a globally prominent human-specific pathogen responsible for an enormous burden of human illnesses, including >600 million pharyngeal and >100 million skin infections each year. Despite intensive efforts that focus on invasive indications, much remains unknown about this bacterium in its natural state during colonization of the nasopharynx and skin. Using acute experimental infection models in HLA-transgenic mice, we evaluated how the hyaluronic acid (HA) capsule contributes to S. pyogenes MGAS8232 infection within these limited biological niches. Herein, we demonstrate that HA capsule expression promotes bacterial burden in murine nasal turbinates and skin lesions by resisting neutrophil-mediated killing. HA capsule production is encoded by the hasABC operon and compared to wildtype S. pyogenes infections, mice infected with a ΔhasA mutant exhibited over a 1000-fold CFU reduction at 48-hours post-nasal challenge, and a 10,000-fold CFU reduction from skin lesions 72-hours post-skin challenge. HA capsule expression contributed substantially to skin lesion size development following subdermal inoculations. In the absence of capsule expression, S. pyogenes revealed drastically impeded growth in whole human blood and increased susceptibility to killing by isolated neutrophils ex vivo, highlighting its important role in resisting phagocytosis. Furthermore, we establish that neutrophil depletion in mice recovered the reduced burden by the ΔhasA mutant in both the nasopharynx and skin. Together, this work confirms that the HA capsule is a key virulence determinant during acute infections by S. pyogenes and demonstrates that its predominant function is to protect S. pyogenes against neutrophil-mediated killing.
Topics: Mice; Humans; Animals; Streptococcus pyogenes; Hyaluronic Acid; Neutrophils; Bacterial Capsules; Streptococcal Infections; Bacterial Proteins; Mice, Transgenic
PubMed: 36449535
DOI: 10.1371/journal.ppat.1011013 -
Infection and Immunity Mar 2018Person-to-person transmission of (the pneumococcus) may occur via environmental sources in close contact with carriers. Pneumococcal polysaccharide capsules, the...
Person-to-person transmission of (the pneumococcus) may occur via environmental sources in close contact with carriers. Pneumococcal polysaccharide capsules, the determinant of serotype (or type), are heterogeneous in structure and amount, and these differences affect rates of transmission. In this study, we examined the contribution of capsule and its variations to the maintenance of pneumococcal viability under starvation conditions. retained its ability to colonize infant mice even after incubation for 24 h in phosphate-buffered saline at 25°C. The expression of capsule by the locus prolonged survival under these and other nutrient-poor conditions. Analysis of capsule-switch constructs showed that strain-to-strain differences in survival were due to capsule type rather than genetic background. The addition of glucose was sufficient to rescue the survival defect of the capsule-deficient derivative, demonstrating that in the absence of capsule, survival depends upon nutrient availability. During starvation, there was a decrease in capsule size and amount of capsular polysaccharide that was dependent on bacterial viability and the presence of the locus. These observations suggest that pneumococci catabolize their own capsular polysaccharide using the genes involved in its biosynthesis to maintain viability when other carbon sources are unavailable. Our findings describe a new role of the pneumococcal capsule: the prolongation of viability under nutrient-limiting conditions as would be encountered during periods when the organism is between hosts.
Topics: Animals; Bacterial Capsules; Mice; Mice, Inbred C57BL; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 29311231
DOI: 10.1128/IAI.00802-17 -
Cell Host & Microbe Jan 2021Glycans, the most diverse biopolymer, are shaped by evolutionary pressures stemming from host-microbe interactions. Here, we present machine learning and bioinformatics...
Glycans, the most diverse biopolymer, are shaped by evolutionary pressures stemming from host-microbe interactions. Here, we present machine learning and bioinformatics methods to leverage the evolutionary information present in glycans to gain insights into how pathogens and commensals interact with hosts. By using techniques from natural language processing, we develop deep-learning models for glycans that are trained on a curated dataset of 19,299 unique glycans and can be used to study and predict glycan functions. We show that these models can be utilized to predict glycan immunogenicity and the pathogenicity of bacterial strains, as well as investigate glycan-mediated immune evasion via molecular mimicry. We also develop glycan-alignment methods and use these to analyze virulence-determining glycan motifs in the capsular polysaccharides of bacterial pathogens. These resources enable one to identify and study glycan motifs involved in immunogenicity, pathogenicity, molecular mimicry, and immune evasion, expanding our understanding of host-microbe interactions.
Topics: Animals; Bacteria; Bacterial Capsules; Bacterial Physiological Phenomena; Computational Biology; Deep Learning; Host Microbial Interactions; Humans; Immune Evasion; Natural Language Processing; Polysaccharides; Polysaccharides, Bacterial; Symbiosis; Virulence
PubMed: 33120114
DOI: 10.1016/j.chom.2020.10.004 -
PLoS Pathogens Aug 2023Among the many oral streptococci, Streptococcus pneumoniae (Spn) stands out for the capacity of encapsulated strains to cause invasive infection. Spread beyond upper...
Among the many oral streptococci, Streptococcus pneumoniae (Spn) stands out for the capacity of encapsulated strains to cause invasive infection. Spread beyond upper airways, however, is a biological dead end for the organism, raising the question of the benefits of expending energy to coat its surface in a thick layer of capsular polysaccharide (CPS). In this study, we compare mutants of two serotypes expressing different amounts of CPS and test these in murine models of colonization, invasion infection and transmission. Our analysis of the effect of CPS amount shows that Spn expresses a capsule of sufficient thickness to shield its surface from the deposition of complement and binding of antibody to underlying epitopes. While effective shielding is permissive for invasive infection, its primary contribution to the organism appears to be in the dynamics of colonization. A thicker capsule increases bacterial retention in the nasopharynx, the first event in colonization, and also impedes IL-17-dependent clearance during late colonization. Enhanced colonization is associated with increased opportunity for host-to-host transmission. Additionally, we document substantial differences in CPS amount among clinical isolates of three common serotypes. Together, our findings show that CPS amount is highly variable among Spn and could be an independent determinant affecting host interactions.
Topics: Animals; Mice; Streptococcus pneumoniae; Streptococcus; Polysaccharides; Nasopharynx; Nose; Pneumococcal Infections; Bacterial Capsules
PubMed: 37540710
DOI: 10.1371/journal.ppat.1011509 -
Microbes and Infection Feb 1999This review summarizes the current knowledge pertaining to the pathogenesis of infection with Bacillus anthracis relative to the two exotoxins and the capsule. Emphasis... (Review)
Review
This review summarizes the current knowledge pertaining to the pathogenesis of infection with Bacillus anthracis relative to the two exotoxins and the capsule. Emphasis is given to the structure and activities of the individual components of the exotoxins, their interaction with cells, and the response of macrophages to lethal toxin. Finally, results from vaccination studies are reviewed.
Topics: Animals; Anthrax; Antigens, Bacterial; Bacillus anthracis; Bacterial Capsules; Bacterial Toxins; Bacterial Vaccines; Humans; Macrophages; Virulence
PubMed: 10594977
DOI: 10.1016/s1286-4579(99)80004-5 -
Microbial Genomics Sep 2018The genus Neisseria comprises a diverse group of commensal bacteria, which typically colonize the mucosal surfaces of humans and other animals. Neisseria meningitidis,...
The genus Neisseria comprises a diverse group of commensal bacteria, which typically colonize the mucosal surfaces of humans and other animals. Neisseria meningitidis, the meningococcus, is notable for its potential to cause invasive meningococcal disease (IMD) in humans; however, IMD is comparatively rare, and meningococci normally colonize the nasopharynx asymptomatically. Possession of a polysaccharide capsule has been shown to be a prerequisite for disease in almost all IMD cases, and was previously considered unique to N. meningitidis, and potentially acquired by horizontal genetic transfer (HGT). Nevertheless, the capsule must also have some role in asymptomatic colonization and/or transmission, consistent with the existence of six non-disease-associated meningococcal capsule serogroups. In this study, full complements of putative capsule genes were identified in non-pathogenic Neisseria species, including Neisseria subflava and Neisseria elongata. These species contained genes for capsule transport and translocation homologous to those of N. meningitidis, as well as novel putative capsule synthesis genes. Phylogenetic analyses were consistent with the proposal that these genes were acquired by the meningococcus through HGT. In contrast with previous evolutionary models, however, the most parsimonious explanation of these data was that capsule transport genes had been lost in the common ancestor of the meningococcus, gonococcus, and their close relatives, and then reacquired by some meningococci. The most likely donor of the meningococcal transport genes was another Neisseria species.
Topics: Bacterial Capsules; Genes, Bacterial; Neisseria; Phylogeny
PubMed: 30074474
DOI: 10.1099/mgen.0.000208