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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 -
Microbiology Spectrum May 2019The chapter about the Gram-positive bacterial cell wall gives a brief historical background on the discovery of Gram-positive cell walls and their constituents and... (Review)
Review
The chapter about the Gram-positive bacterial cell wall gives a brief historical background on the discovery of Gram-positive cell walls and their constituents and microscopic methods applied for studying the Gram-positive cell envelope. Followed by the description of the different chemical building blocks of peptidoglycan and the biosynthesis of the peptidoglycan layers and high turnover of peptidoglycan during bacterial growth. Lipoteichoic acids and wall teichoic acids are highlighted as major components of the cell wall. Characterization of capsules and the formation of extracellular vesicles by Gram-positive bacteria close the section on cell envelopes which have a high impact on bacterial pathogenesis. In addition, the specialized complex and unusual cell wall of mycobacteria is introduced thereafter. Next a short back view is given on the development of electron microscopic examinations for studying bacterial cell walls. Different electron microscopic techniques and methods applied to examine bacterial cell envelopes are discussed in the view that most of the illustrated methods should be available in a well-equipped life sciences orientated electron microscopic laboratory. In addition, newly developed and mostly well-established cryo-methods like high-pressure freezing and freeze-substitution (HPF-FS) and cryo-sections of hydrated vitrified bacteria (CEMOVIS, Cryo-electron microscopy of vitreous sections) are described. At last, modern cryo-methods like cryo-electron tomography (CET) and cryo-FIB-SEM milling (focus ion beam-scanning electron microscopy) are introduced which are available only in specialized institutions, but at present represent the best available methods and techniques to study Gram-positive cell walls under close-to-nature conditions in great detail and at high resolution.
Topics: Bacterial Capsules; Bacteriological Techniques; Cell Membrane; Cell Wall; Cryoelectron Microscopy; Electron Microscope Tomography; Extracellular Vesicles; Freezing; Gram-Positive Bacteria; Imaging, Three-Dimensional; Lipopolysaccharides; Microscopy, Electron; Microscopy, Electron, Transmission; Mycobacterium; Peptidoglycan; Teichoic Acids
PubMed: 31124431
DOI: 10.1128/microbiolspec.GPP3-0044-2018 -
Microbiology Spectrum Jun 2015Microbes produce a biofilm matrix consisting of proteins, extracellular DNA, and polysaccharides that is integral in the formation of bacterial communities. Historical... (Review)
Review
Microbes produce a biofilm matrix consisting of proteins, extracellular DNA, and polysaccharides that is integral in the formation of bacterial communities. Historical studies of polysaccharides revealed that their overproduction often alters the colony morphology and can be diagnostic in identifying certain species. The polysaccharide component of the matrix can provide many diverse benefits to the cells in the biofilm, including adhesion, protection, and structure. Aggregative polysaccharides act as molecular glue, allowing the bacterial cells to adhere to each other as well as surfaces. Adhesion facilitates the colonization of both biotic and abiotic surfaces by allowing the bacteria to resist physical stresses imposed by fluid movement that could separate the cells from a nutrient source. Polysaccharides can also provide protection from a wide range of stresses, such as desiccation, immune effectors, and predators such as phagocytic cells and amoebae. Finally, polysaccharides can provide structure to biofilms, allowing stratification of the bacterial community and establishing gradients of nutrients and waste products. This can be advantageous for the bacteria by establishing a heterogeneous population that is prepared to endure stresses created by the rapidly changing environments that many bacteria encounter. The diverse range of polysaccharide structures, properties, and roles highlight the importance of this matrix constituent to the successful adaptation of bacteria to nearly every niche. Here, we present an overview of the current knowledge regarding the diversity and benefits that polysaccharide production provides to bacterial communities within biofilms.
Topics: Alginates; Bacteria; Bacterial Adhesion; Bacterial Capsules; Biofilms; Cellulose; Extracellular Matrix; Fructans; Glucuronic Acid; Hexuronic Acids; Polysaccharides; Polysaccharides, Bacterial
PubMed: 26185074
DOI: 10.1128/microbiolspec.MB-0011-2014 -
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 -
Clinical Microbiology Reviews Jul 2015Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host... (Review)
Review
Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.
Topics: Bacterial Capsules; Bacterial Vaccines; Genome, Bacterial; Immunity, Innate; Polysaccharides, Bacterial; Serogroup; Streptococcus pneumoniae
PubMed: 26085553
DOI: 10.1128/CMR.00024-15 -
Frontiers in Cellular and Infection... 2017is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias,... (Review)
Review
is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent , generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent , this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.
Topics: Bacteremia; Bacterial Capsules; Bacterial Proteins; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Humans; Hydroxamic Acids; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Molecular Epidemiology; Phylogeography; Serogroup; Urinary Tract Infections; Virulence; Virulence Factors
PubMed: 29209595
DOI: 10.3389/fcimb.2017.00483 -
Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria.The Journal of Experimental Medicine Apr 2022Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo...
Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) "untouchable" for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.
Topics: Animals; Bacterial Capsules; Capsules; Kupffer Cells; Liver; Mice; Pneumococcal Infections; Streptococcus pneumoniae; Virulence
PubMed: 35258552
DOI: 10.1084/jem.20212032