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Microbiology Spectrum Nov 2019is a Gram-Positive pathogen that is a major causative agent of pneumonia, otitis media, sepsis and meningitis across the world. The World Health Organization estimates... (Review)
Review
is a Gram-Positive pathogen that is a major causative agent of pneumonia, otitis media, sepsis and meningitis across the world. The World Health Organization estimates that globally over 500,000 children are killed each year by this pathogen. Vaccines offer the best protection against infections. The current polysaccharide conjugate vaccines have been very effective in reducing rates of invasive pneumococcal disease caused by vaccine type strains. However, the effectiveness of these vaccines have been somewhat diminished by the increasing numbers of cases of invasive disease caused by non-vaccine type strains, a phenomenon known as serotype replacement. Since, there are currently at least 98 known serotypes of , it may become cumbersome and expensive to add many additional serotypes to the current 13-valent vaccine, to circumvent the effect of serotype replacement. Hence, alternative serotype independent strategies, such as vaccination with highly cross-reactive pneumococcal protein antigens, should continue to be investigated to address this problem. This chapter provides a comprehensive discussion of pneumococcal vaccines past and present, protein antigens that are currently under investigation as vaccine candidates, and other alternatives, such as the pneumococcal whole cell vaccine, that may be successful in reducing current rates of disease caused by .
Topics: Animals; Bacterial Proteins; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 31858954
DOI: 10.1128/microbiolspec.GPP3-0028-2018 -
Virulence Dec 2021Bacterial proteases and peptidases are integral to cell physiology and stability, and their necessity in is no exception. Protein cleavage and processing mechanisms... (Review)
Review
Bacterial proteases and peptidases are integral to cell physiology and stability, and their necessity in is no exception. Protein cleavage and processing mechanisms within the bacterial cell serve to ensure that the cell lives and functions in its commensal habitat and can respond to new environments presenting stressful conditions. For , the human nasopharynx is its natural habitat. In the context of virulence, movement of to the lungs, blood, or other sites can instigate responses by the bacteria that result in their proteases serving dual roles of self-protein processors and virulence factors of host protein targets.
Topics: Animals; Bacterial Proteins; Genome, Bacterial; Humans; Immune Evasion; Lung; Mice; Nasopharynx; Peptide Hydrolases; Streptococcus pneumoniae; Virulence; Virulence Factors
PubMed: 33660565
DOI: 10.1080/21505594.2021.1889812 -
Frontiers in Cellular and Infection... 2022Host innate and adaptive immunity to infection with is critically dependent on the complement system, demonstrated by the high incidence of invasive infection in... (Review)
Review
Host innate and adaptive immunity to infection with is critically dependent on the complement system, demonstrated by the high incidence of invasive infection in people with inherited deficiency of complement components. The complement system is activated by through multiple mechanisms. The classical complement pathway is activated by recognition of by C-reactive protein, serum amyloid P, C1q, SIGN-R1, or natural or acquired antibody. Some strains are also recognised by ficolins to activate the mannose binding lectin (MBL) activation pathway. Complement activation is then amplified by the alternative complement pathway, which can also be activated by directly. Complement activation results in covalent linkage of the opsonic complement factors C3b and iC3b to the surface which promote phagocytic clearance, along with complement-mediated immune adherence to erythrocytes, thereby protecting against septicaemia. The role of complement for mucosal immunity to is less clear. Given the major role of complement in controlling infection with , it is perhaps unsurprising that has evolved multiple mechanisms of complement evasion, including the capsule, multiple surface proteins, and the toxin pneumolysin. There is considerable variation between capsular serotypes and genotypes with regards to sensitivity to complement which correlates with ability to cause invasive infections. However, at present we only have a limited understanding of the main mechanisms causing variations in complement sensitivity between strains and to non-pathogenic streptococci.
Topics: Complement Activation; Complement System Proteins; Humans; Streptococcus pneumoniae
PubMed: 35967850
DOI: 10.3389/fcimb.2022.929483 -
European Journal of Clinical... Dec 2020The Mitis group of streptococci includes an important human pathogen, Streptococcus pneumoniae (pneumococcus) and about 20 other related species with much lower... (Review)
Review
The Mitis group of streptococci includes an important human pathogen, Streptococcus pneumoniae (pneumococcus) and about 20 other related species with much lower pathogenicity. In clinical practice, some representatives of these species, especially Streptococcus pseudopneumoniae and Streptococcus mitis, are sometimes mistaken for S. pneumoniae based on the results of classical microbiological methods, such as optochin susceptibility and bile solubility. Several various molecular approaches that address the issue of correct identification of pneumococci and other Mitis streptococci have been proposed and are discussed in this review, including PCR- and gene sequencing-based tests as well as new developments in the genomic field that represents an important advance in our understanding of relationships within the Mitis group.
Topics: Automation; Humans; Multilocus Sequence Typing; Phenotype; Polymerase Chain Reaction; Streptococcus mitis; Streptococcus pneumoniae; Whole Genome Sequencing
PubMed: 32710352
DOI: 10.1007/s10096-020-03991-9 -
Cell Host & Microbe Jan 2021Streptococcus pneumoniae is an opportunistic human pathogen that causes invasive diseases, including pneumonia, with greater health risks upon influenza A virus (IAV)...
Streptococcus pneumoniae is an opportunistic human pathogen that causes invasive diseases, including pneumonia, with greater health risks upon influenza A virus (IAV) co-infection. To facilitate pathogenesis studies in vivo, we developed an inducible CRISPR interference system that enables genome-wide fitness testing in one sequencing step (CRISPRi-seq). We applied CRISPRi-seq to assess bottlenecks and identify pneumococcal genes important in a murine pneumonia model. A critical bottleneck occurs at 48 h with few bacteria causing systemic infection. This bottleneck is not present during IAV superinfection, facilitating identification of pneumococcal pathogenesis-related genes. Top in vivo essential genes included purA, encoding adenylsuccinate synthetase, and the cps operon required for capsule production. Surprisingly, CRISPRi-seq indicated no fitness-related role for pneumolysin during superinfection. Interestingly, although metK (encoding S-adenosylmethionine synthetase) was essential in vitro, it was dispensable in vivo. This highlights advantages of CRISPRi-seq over transposon-based genetic screens, as all genes, including essential genes, can be tested for pathogenesis potential.
Topics: Adenylosuccinate Synthase; Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Female; Genes, Bacterial; Genetic Fitness; High-Throughput Nucleotide Sequencing; Influenza A virus; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Operon; Orthomyxoviridae Infections; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Superinfection
PubMed: 33120116
DOI: 10.1016/j.chom.2020.10.001 -
Cells Mar 2022Systemic infections with pathogenic or facultative pathogenic bacteria are associated with activation and aggregation of platelets leading to thrombocytopenia and... (Review)
Review
Systemic infections with pathogenic or facultative pathogenic bacteria are associated with activation and aggregation of platelets leading to thrombocytopenia and activation of the clotting system. Bacterial proteins leading to platelet activation and aggregation have been identified, and while platelet receptors are recognized, induced signal transduction cascades are still often unknown. In addition to proteinaceous adhesins, pathogenic bacteria such as and also produce toxins such as pneumolysin and alpha-hemolysin. They bind to cellular receptors or form pores, which can result in disturbance of physiological functions of platelets. Here, we discuss the bacteria-platelet interplay in the context of adhesin-receptor interactions and platelet-activating bacterial proteins, with a main emphasis on and . More importantly, we summarize recent findings of how toxins and the pore-forming toxin pneumolysin of interfere with platelet function. Finally, the relevance of platelet dysfunction due to killing by toxins and potential treatment interventions protecting platelets against cell death are summarized.
Topics: Adhesins, Bacterial; Bacterial Proteins; Blood Platelets; Staphylococcus aureus; Streptococcus pneumoniae
PubMed: 35406684
DOI: 10.3390/cells11071121 -
Frontiers in Cellular and Infection... 2022The gram-positive bacterium is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts... (Review)
Review
The gram-positive bacterium is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts are primarily pneumococcal conjugate vaccines that target the bacterial capsule polysaccharide, as well as antibiotics for pathogen clearance. While these methods have been enormously effective at disease prevention and treatment, there has been an emergence of non-vaccine serotypes, termed serotype replacement, and increasing antibiotic resistance among these serotypes. To combat , the immune system must deploy an arsenal of antimicrobial functions. However, has evolved a repertoire of evasion techniques and is able to modulate the host immune system. Antibodies are a key component of pneumococcal immunity, targeting both the capsule polysaccharide and protein antigens on the surface of the bacterium. These antibodies have been shown to play a variety of roles including increasing opsonophagocytic activity, enzymatic and toxin neutralization, reducing bacterial adherence, and altering bacterial gene expression. In this review, we describe targets of anti-pneumococcal antibodies and describe antibody functions and effectiveness against .
Topics: Adult; Antibodies, Bacterial; Child; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 35155281
DOI: 10.3389/fcimb.2022.824788 -
PLoS Pathogens Oct 2020Gram-positive bacteria employ an array of secreted peptides to control population-level behaviors in response to environmental cues. We review mechanistic and functional... (Review)
Review
Gram-positive bacteria employ an array of secreted peptides to control population-level behaviors in response to environmental cues. We review mechanistic and functional features of secreted peptides produced by the human pathogen Streptococcus pneumoniae. We discuss sequence features, mechanisms of transport, and receptors for 3 major categories of small peptides: the double-glycine peptides, the Rap, Rgg, NprR, PlcR, and PrgX (RRNPP)-binding peptides, and the lanthionine-containing peptides. We highlight the impact of factors that contribute to carriage and pathogenesis, specifically genetic diversity, microbial competition, biofilm development, and environmental adaptation. A recent expansion in pneumococcal peptide studies reveals a complex network of interacting signaling systems where multiple peptides are integrated into the same signaling pathway, allowing multiple points of entry into the pathway and extending information content in new directions. In addition, since peptides are present in the extracellular milieu, there are opportunities for crosstalk, quorum sensing (QS), as well as intra- and interstrain and species interactions. Knowledge on the manner that population-level behaviors contribute to disease provides an avenue for the design and development of anti-infective strategies.
Topics: Animals; Bacterial Proteins; Environment; Gene Expression Regulation, Bacterial; Gram-Positive Bacteria; Humans; Quorum Sensing; Streptococcus pneumoniae
PubMed: 33119698
DOI: 10.1371/journal.ppat.1008931 -
Frontiers in Cellular and Infection... 2020Meningitis, the inflammation of the protective membrane surrounding the brain and spinal cord (known as meninges), is a condition associated with high mortality rates... (Review)
Review
Meningitis, the inflammation of the protective membrane surrounding the brain and spinal cord (known as meninges), is a condition associated with high mortality rates and permanent neurological sequelae in a significant proportion of survivors. The opportunistic pathogen (SPN/pneumococcus) is the leading cause of bacterial meningitis in adults and older children. Following infection of the lower respiratory tract and subsequent bloodstream invasion, SPN breaches the blood-brain barrier endothelium for invasion of the central nervous system. Transcytosis, a mode of passage through the endothelial cells has been identified as the predominant route of pneumococcal blood-brain barrier trafficking. Herein, we review the interactions enabling SPN invasion into the brain endothelial cells, events involved in the tug-of-war between pneumococcal virulence factors and host intracellular defense machineries and pneumococcal strategies for evasion of host defenses and successful transendothelial trafficking.
Topics: Adolescent; Blood-Brain Barrier; Brain; Child; Endothelial Cells; Endothelium; Humans; Streptococcus pneumoniae
PubMed: 33224900
DOI: 10.3389/fcimb.2020.590682 -
Journal of Infection in Developing... May 2021Streptococcus pneumoniae can be responsible for severe human infections. Optochin resistance has been a potential cause of misidentification of pneumococcus and other...
INTRODUCTION
Streptococcus pneumoniae can be responsible for severe human infections. Optochin resistance has been a potential cause of misidentification of pneumococcus and other members of the mitis group. Hence, rapid and easy optochin resistant (Optr) S. pneumoniae identification is essential.
METHODOLOGY
Atypical pneumococci were characterized using optochin susceptibility, bile solubility based on spectrophotometric reading, serotyping, pulsed field gel electrophoresis (PFGE), 16S rRNA sequencing and PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802 and Spn9828.
RESULTS
Optical density values for the bile solubility test suggest the identification of four Optr S. pneumoniae and one Streptococcus pseudopneumoniae. All Optr pneumococci harbored cpsA, lytA, ply, Spn9802, Spn9828 and pspA genes. Only ply, spn9802 and Spn9828 genes were detected in S. pseudopneumoniae. The 16S rRNA sequencing differentiates between these two species. Optr S. pneumoniae strains belonged to different genotypes and serotypes (14, 19A, 3 and 9V). Three Optr S. pneumoniae isolates were typed as pspA family 2, while one belonged to pspA family 1. Sequencing of the atpA and atpC gene of the Optr variants revealed three mutations in the ATPase a-subunit (L99I, M23V and V52I) and one mutation in ATPase c-subunit (V48I).
CONCLUSIONS
Our data indicate that bile OD-values provides an accurate, fast and easy method to discriminate between Optr S. pneumoniae and other Streptococcus mitis group. Moreover molecular techniques, confirming the bile test, can be used in order to prevent these atypical pneumococci and alert clinical microbiologists of the presence of these strains in the community.
Topics: Drug Resistance, Bacterial; Genes, Bacterial; Genotype; Humans; Microbial Sensitivity Tests; Molecular Diagnostic Techniques; Quinine; RNA, Ribosomal, 16S; Streptococcal Infections; Streptococcus; Streptococcus pneumoniae; Tunisia
PubMed: 34106891
DOI: 10.3855/jidc.13106