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Microbiology Spectrum Mar 2019The polysaccharide capsule of is the dominant surface structure of the organism and plays a critical role in virulence, principally by interfering with host... (Review)
Review
The polysaccharide capsule of is the dominant surface structure of the organism and plays a critical role in virulence, principally by interfering with host opsonophagocytic clearance mechanisms. The capsule is the target of current pneumococcal vaccines, but there are 98 currently recognised polysaccharide serotypes and protection is strictly serotype-specific. Widespread use of these vaccines is driving changes in serotype prevalence in both carriage and disease. This chapter summarises current knowledge on the role of the capsule and its regulation in pathogenesis, the mechanisms of capsule synthesis, the genetic basis for serotype differences, and provides insights into how so many structurally distinct capsular serotypes have evolved. Such knowledge will inform ongoing refinement of pneumococcal vaccination strategies.
Topics: Animals; Bacterial Capsules; Humans; Pneumococcal Vaccines; Polysaccharides, Bacterial; Streptococcus pneumoniae
PubMed: 30977464
DOI: 10.1128/microbiolspec.GPP3-0019-2018 -
Microbiology and Molecular Biology... Sep 2016Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae... (Review)
Review
Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore, K. pneumoniae strains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity in K. pneumoniae strains, and not every factor plays the same critical role in all virulent Klebsiella strains. Recent studies have identified additional K. pneumoniae virulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.
Topics: Anti-Bacterial Agents; Bacterial Capsules; Bacterial Outer Membrane Proteins; Drug Resistance, Multiple, Bacterial; Fimbriae, Bacterial; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Siderophores; Virulence Factors
PubMed: 27307579
DOI: 10.1128/MMBR.00078-15 -
Current Opinion in Microbiology Apr 2020For ∼30 years, two distinct groups of clinical isolates of Klebsiella pneumoniae have been recognized. Classical strains (cKp) are typically isolated from patients... (Review)
Review
For ∼30 years, two distinct groups of clinical isolates of Klebsiella pneumoniae have been recognized. Classical strains (cKp) are typically isolated from patients with some degree of immunocompromise and are not virulent in mouse models of infection whereas hypervirulent strains (hvKp) are associated with community acquired invasive infections and are highly virulent in mouse models of infection. Hyperproduction of capsule and a hypermucoviscous colony phenotype have been strongly associated with the hypervirulence of hvKp strains. Recent studies have begun to elucidate the relationship between capsule gene expression, hypermucoviscosity and hypervirulence. Additionally, genes associated with hyperproduction of capsule and hypermucoviscosity in hvKp strains have been identified in a few cKp isolates. However, it is not clear how the acquisition of these genes impacts the virulence of cKp isolates. A better understanding of the potential risks of these strains is particularly important given that many of them are resistant to multiple antibiotics, including carbapenems.
Topics: Animals; Bacterial Capsules; Bacterial Proteins; Gene Expression Regulation, Bacterial; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mutation; Virulence; Virulence Factors
PubMed: 32062153
DOI: 10.1016/j.mib.2020.01.006 -
The Biochemical Journal Jul 2019Bacterial capsules have evolved to be at the forefront of the cell envelope, making them an essential element of bacterial biology. Efforts to understand the (Mtb)... (Review)
Review
Bacterial capsules have evolved to be at the forefront of the cell envelope, making them an essential element of bacterial biology. Efforts to understand the (Mtb) capsule began more than 60 years ago, but the relatively recent development of mycobacterial genetics combined with improved chemical and immunological tools have revealed a more refined view of capsule molecular composition. A glycogen-like α-glucan is the major constituent of the capsule, with lower amounts of arabinomannan and mannan, proteins and lipids. The major Mtb capsular components mediate interactions with phagocytes that favor bacterial survival. Vaccination approaches targeting the mycobacterial capsule have proven successful in controlling bacterial replication. Although the Mtb capsule is composed of polysaccharides of relatively low complexity, the concept of antigenic variability associated with this structure has been suggested by some studies. Understanding how Mtb shapes its envelope during its life cycle is key to developing anti-infective strategies targeting this structure at the host-pathogen interface.
Topics: Bacterial Capsules; Humans; Lipids; Mycobacterium tuberculosis; Polysaccharides, Bacterial; Tuberculosis Vaccines
PubMed: 31320388
DOI: 10.1042/BCJ20190324 -
Microbiology Spectrum Feb 2016Strains of Klebsiella pneumoniae are frequently opportunistic pathogens implicated in urinary tract and catheter-associated urinary-tract infections of hospitalized...
Strains of Klebsiella pneumoniae are frequently opportunistic pathogens implicated in urinary tract and catheter-associated urinary-tract infections of hospitalized patients and compromised individuals. Infections are particularly difficult to treat since most clinical isolates exhibit resistance to several antibiotics leading to treatment failure and the possibility of systemic dissemination. Infections of medical devices such as urinary catheters is a major site of K. pneumoniae infections and has been suggested to involve the formation of biofilms on these surfaces. Over the last decade there has been an increase in research activity designed to investigate the pathogenesis of K. pneumoniae in the urinary tract. These investigations have begun to define the bacterial factors that contribute to growth and biofilm formation. Several virulence factors have been demonstrated to mediate K. pneumoniae infectivity and include, but are most likely not limited to, adherence factors, capsule production, lipopolysaccharide presence, and siderophore activity. The development of both in vitro and in vivo models of infection will lead to further elucidation of the molecular pathogenesis of K. pneumoniae. As for most opportunistic infections, the role of host factors as well as bacterial traits are crucial in determining the outcome of infections. In addition, multidrug-resistant strains of these bacteria have become a serious problem in the treatment of Klebsiella infections and novel strategies to prevent and inhibit bacterial growth need to be developed. Overall, the frequency, significance, and morbidity associated with K. pneumoniae urinary tract infections have increased over many years. The emergence of these bacteria as sources of antibiotic resistance and pathogens of the urinary tract present a challenging problem for the clinician in terms of management and treatment of individuals.
Topics: Bacterial Capsules; Biofilms; Fimbriae, Bacterial; Humans; Iron; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Siderophores; Urease; Urinary Tract Infections; Virulence
PubMed: 26999397
DOI: 10.1128/microbiolspec.UTI-0005-2012 -
Trends in Microbiology Dec 2018Bacterial pathogens and commensals are surrounded by diverse surface polysaccharides which include capsules and lipopolysaccharides. These carbohydrates play a vital... (Review)
Review
Bacterial pathogens and commensals are surrounded by diverse surface polysaccharides which include capsules and lipopolysaccharides. These carbohydrates play a vital role in bacterial ecology and interactions with the environment. Here, we review recent rapid advancements in this field, which have improved our understanding of the roles, structures, and genetics of bacterial polysaccharide antigens. Genetic loci encoding the biosynthesis of these antigens may have evolved as bacterial diversity-generating machines, driven by selection from a variety of forces, including host immunity, bacteriophages, and cell-cell interactions. We argue that the high adaptive potential of polysaccharide antigens should be taken into account in the design of polysaccharide-targeting medical interventions like conjugate vaccines and phage-based therapies.
Topics: Animals; Antigens, Bacterial; Bacteria; Bacterial Capsules; Biodiversity; Cell Communication; Ecology; Evolution, Molecular; Genetic Loci; Humans; Immunity; Lipopolysaccharides; Phage Therapy; Polysaccharides; Polysaccharides, Bacterial; Serotyping; Symbiosis; Vaccines, Conjugate
PubMed: 30037568
DOI: 10.1016/j.tim.2018.06.006 -
Microbiology and Molecular Biology... May 2020is a tier 1 select agent responsible for tularemia in humans and a wide variety of animal species. Extensive research into understanding the virulence factors of the... (Review)
Review
is a tier 1 select agent responsible for tularemia in humans and a wide variety of animal species. Extensive research into understanding the virulence factors of the bacterium has been ongoing to develop an efficacious vaccine. At least two such virulence factors are described as capsules of : the O-antigen capsule and the capsule-like complex (CLC). These two separate entities aid in avoiding host immune defenses but have not been clearly differentiated. These components are distinct and differ in composition and genetic basis. The O-antigen capsule consists of a polysaccharide nearly identical to the lipopolysaccharide (LPS) O antigen, whereas the CLC is a heterogeneous complex of glycoproteins, proteins, and possibly outer membrane vesicles and tubes (OMV/Ts). In this review, the current understanding of these two capsules is summarized, and the historical references to "capsules" of are clarified. A significant amount of research has been invested into the composition of each capsule and the genes involved in synthesis of the polysaccharide portion of each capsule. Areas of future research include further exploration into the molecular regulation and pathways responsible for expression of each capsule and further elucidating the role that each capsule plays in virulence.
Topics: Animals; Bacterial Capsules; Francisella tularensis; Humans; Polysaccharides, Bacterial; Tularemia; Virulence; Virulence Factors
PubMed: 32051235
DOI: 10.1128/MMBR.00065-19 -
NPJ Biofilms and Microbiomes Mar 2024In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability to infect the host.... (Review)
Review
In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability to infect the host. The capsules, polymers that bacteria secrete near their cell wall, participates in numerous bacterial life processes and plays a crucial role in resisting host immune attacks and adapting to their niche. Here, we discuss the relationship between capsules and bacterial virulence, summarizing the molecular mechanisms of capsular regulation and pathogenesis to provide new insights into the research on the pathogenesis of pathogenic bacteria.
Topics: Bacterial Capsules; Virulence; Bacteria
PubMed: 38480745
DOI: 10.1038/s41522-024-00497-6 -
Discovery and Characterization of Pneumococcal Serogroup 36 Capsule Subtypes, Serotypes 36A and 36B.Journal of Clinical Microbiology Apr 2023Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target...
Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized. Prior sequence analysis of pneumococcal capsule synthesis () loci suggested the existence of capsule subtypes among isolates identified as "serotype 36" according to conventional capsule typing methods. We discovered these subtypes represent two antigenically similar but distinguishable pneumococcal capsule serotypes, 36A and 36B. Biochemical analysis of their capsule PS structure reveals that both have the shared repeat unit backbone [→5)-α-d-Gal-(1→1)-d-Rib-ol-(5→P→6)-β-d-ManNAc-(1→4)-β-d-Glc-(1→] with two branching structures. Both serotypes have a β-d-Gal branch to Ribitol. Serotypes 36A and 36B differ by the presence of a α-d-Glc-(1→3)-β-d-ManNAc or α-d-Gal-(1→3)-β-d-ManNAc branch, respectively. Comparison of the phylogenetically distant serogroup 9 and 36 loci, which all encode this distinguishing glycosidic bond, revealed that the incorporation of Glc (in types 9N and 36A) versus Gal (in types 9A, 9V, 9L, and 36B) is associated with the identity of four amino acids in the encoded glycosyltransferase WcjA. Identifying functional determinants of -encoded enzymes and their impact on capsule PS structure is key to improving the resolution and reliability of sequencing-based capsule typing methods and discovering novel capsule variants indistinguishable by conventional serotyping methods.
Topics: Humans; Streptococcus pneumoniae; Serogroup; Reproducibility of Results; Serotyping; Polysaccharides; Pneumococcal Vaccines; Bacterial Capsules; Pneumococcal Infections
PubMed: 36971549
DOI: 10.1128/jcm.00024-23 -
Journal of Neuroinflammation May 2019Streptococcus pneumoniae is the cause of a highly lethal form of meningitis in humans. Microglial cells in the brain represent the first line of defense against...
BACKGROUND
Streptococcus pneumoniae is the cause of a highly lethal form of meningitis in humans. Microglial cells in the brain represent the first line of defense against pathogens, and they participate in the inflammatory response. The cholesterol-dependent cytolysin pneumolysin and the bacterial capsule are key pathogenic factors, known to exacerbate the course of pneumococcal meningitis.
METHODS
We utilized live imaging and immunostaining of glial cells in dissociated and acute brain slice cultures to study the effect of pneumococcal factors, including the cholesterol-dependent cytolysin pneumolysin and the pneumococcal capsule, on microglial motility and taxis.
RESULTS
In brain tissue, primary microglia cells showed an enhanced response towards lysates from bacteria lacking capsules and pneumolysin as they moved rapidly to areas with an abundance of bacterial factors. The presence of bacterial capsules and pneumolysin cumulatively inhibited microglial taxis. In mixed cultures of astrocytes and microglia, the motility of microglia was inhibited by capsular components within minutes after exposure. The reduced motility was partially reversed by mannan, a mannose receptor inhibitor. The effects on microglia were not mediated by astrocytes because pure microglial cells responded to various pneumococcal lysates similarly with distinct cell shape changes as seen in mixed cultures.
CONCLUSIONS
Our data indicate that microglia possess the capacity for a very agile response towards bacterial pathogens, but key pathogenic factors, such as pneumococcal capsules and pneumolysin, inhibited this response shortly after a bacterial challenge. Furthermore, we demonstrate for the first time that the bacterial capsule affects cellular behaviors such as motility and taxis.
Topics: Animals; Bacterial Capsules; Bacterial Proteins; Cell Movement; Cells, Cultured; Chemotaxis; Coculture Techniques; Mice; Mice, Inbred C57BL; Microglia; Organ Culture Techniques; Streptococcus pneumoniae; Streptolysins
PubMed: 31103037
DOI: 10.1186/s12974-019-1491-7