Molecular and structural basis of oligopeptide recognition by the Ami transporter system in pneumococci.

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids.

Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria.

Unlabelled: Pneumococcal pneumonia causes cytotoxicity in the lung parenchyma but the underlying mechanism involves multiple factors contributing to cell death. Here, we discovered that hydrogen peroxide produced by (Spn-H O ) plays a pivotal role by oxidizing hemoglobin, leading to its polymerization and subsequent release of labile heme. At physiologically relevant levels, heme selected a population of encapsulated pneumococci.

Oligopeptide Transporters of Nonencapsulated Streptococcus pneumoniae Regulate CbpAC and PspA Expression and Reduce Complement-Mediated Clearance.

Streptococcus pneumoniae colonizes the human nasopharynx and causes several diseases. Pneumococcal vaccines target the polysaccharide capsule and prevent most serious disease, but there has been an increase in the prevalence of nonencapsulated S. pneumoniae (NESp).

If Not Now, When? Nonserotype Pneumococcal Protein Vaccines.

The sudden emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have greatly accelerated the adoption of novel vaccine strategies, which otherwise would have likely languished for years. In this light, vaccines for certain other pathogens could certainly benefit from reconsideration. One such pathogen is (pneumococcus), an encapsulated bacterium that can express >100 antigenically distinct serotypes.

Prophylactic Inhibition of Colonization by Streptococcus pneumoniae with the Secondary Bile Acid Metabolite Deoxycholic Acid.

Streptococcus pneumoniae colonizes the nasopharynx of children and the elderly but also kills millions worldwide yearly. The secondary bile acid metabolite deoxycholic acid (DoC) affects the viability of human pathogens but also plays multiple roles in host physiology. We assessed the antimicrobial activity of DoC and investigated its potential to eradicate S.

Hydrogen Peroxide Production by Streptococcus pneumoniae Results in Alpha-hemolysis by Oxidation of Oxy-hemoglobin to Met-hemoglobin.

and other streptococci produce a greenish halo on blood agar plates referred to as alpha-hemolysis. This phenotype is utilized by clinical microbiology laboratories to report culture findings of alpha-hemolytic streptococci, including , and other bacteria. The alpha-hemolysis halo on blood agar plates has been related to the hemolytic activity of pneumococcal pneumolysin (Ply) or, to a lesser extent, to lysis of erythrocytes by -produced hydrogen peroxide.

Transformation of nonencapsulated Streptococcus pneumoniae during systemic infection.

Streptococcus pneumoniae (pneumococcus) is a principal cause of bacterial middle ear infections, pneumonia, and meningitis. Capsule-targeted pneumococcal vaccines have likely contributed to increased carriage of nonencapsulated S. pneumoniae (NESp).

Oxidative killing of encapsulated and nonencapsulated Streptococcus pneumoniae by lactoperoxidase-generated hypothiocyanite.

Streptococcus pneumoniae (Pneumococcus) infections affect millions of people worldwide, cause serious mortality and represent a major economic burden. Despite recent successes due to pneumococcal vaccination and antibiotic use, Pneumococcus remains a significant medical problem. Airway epithelial cells, the primary responders to pneumococcal infection, orchestrate an extracellular antimicrobial system consisting of lactoperoxidase (LPO), thiocyanate anion and hydrogen peroxide (H2O2).

The Modified Surface Killing Assay Distinguishes between Protective and Nonprotective Antibodies to PspA.

Pneumococcal surface protein A (PspA) elicits antibody protective against lethal challenge by and is a candidate noncapsular antigen for inclusion in vaccines. Evaluation of immunity to PspA in human trials would be greatly facilitated by an functional assay able to distinguish protective from nonprotective antibodies to PspA. Mouse monoclonal antibodies (MAbs) to PspA can mediate killing by human granulocytes in the modified surface killing assay (MSKA).

Pulmonary Disease Associated With Nonencapsulated .

We discuss 3 patients presenting with pneumonia associated with nonencapsulated (NESp), an emerging pathogen commonly causing upper respiratory infections. Clinical isolates obtained from these patients were characterized to evaluate their respective antibiotic resistance and virulence mechanisms. We demonstrate that NESp resistant to classical drug treatments are isolated during pneumonia.

Protease IV Exacerbates Pneumococcal Pneumonia and Systemic Disease.

Pneumonia is a pulmonary disease affecting people of all ages and is consistently a leading cause of childhood mortality and adult hospitalizations. and are major lung pathogens commonly associated with community-acquired and nosocomial pneumonia. Additionally, mixed lung infections involving these bacterial pathogens are increasing in prevalence and are frequently more severe than single infections.

Increased Virulence of an Encapsulated Streptococcus pneumoniae Upon Expression of Pneumococcal Surface Protein K.

Background: Current Streptococcus pneumoniae vaccines selectively target capsular polysaccharide of specific serotypes, leading to an increase in nonencapsulated S. pneumoniae (NESp). Cocolonization by encapsulated pneumococci and NESp increases the opportunity for intraspecies genetic exchange.

Mucosal Infections and Invasive Potential of Nonencapsulated Are Enhanced by Oligopeptide Binding Proteins AliC and AliD.

Nonencapsulated (NESp) is an emerging human pathogen that colonizes the nasopharynx and is associated with noninvasive diseases such as otitis media (OM), conjunctivitis, and nonbacteremic pneumonia. Since capsule expression was previously thought to be necessary for establishment of invasive pneumococcal disease (IPD), serotype-specific polysaccharide capsules are targeted by currently licensed pneumococcal vaccines. Yet, NESp expressing oligopeptide binding proteins AliC and AliD have been isolated during IPD.

Polyamine transporter potABCD is required for virulence of encapsulated but not nonencapsulated Streptococcus pneumoniae.

Streptococcus pneumoniae is commonly found in the human nasopharynx and is the causative agent of multiple diseases. Since invasive pneumococcal infections are associated with encapsulated pneumococci, the capsular polysaccharide is the target of licensed pneumococcal vaccines. However, there is an increasing distribution of non-vaccine serotypes, as well as nonencapsulated S.

Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release.

Background: Streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. Certain aspects of S. pneumoniae's virulence are dependent upon expression and release of the protein toxin pneumolysin (PLY) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (SpxB).

Surface Proteins and Pneumolysin of Encapsulated and Nonencapsulated Streptococcus pneumoniae Mediate Virulence in a Chinchilla Model of Otitis Media.

Streptococcus pneumoniae infections result in a range of human diseases and are responsible for almost one million deaths annually. Pneumococcal disease is mediated in part through surface structures and an anti-phagocytic capsule. Recent studies have shown that nonencapsulated S.

Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease.

Nonencapsulated Streptococcus pneumoniae as a cause of chronic adenoiditis.

Streptococcus pneumoniae is an important human pathogen. To cause disease, it must first colonize the nasopharynx. The widespread use of pneumococcal-conjugate vaccines which target the capsular polysaccharide has led to decreased nasopharyngeal carriage of vaccine serotypes, but a concomitant increase in carriage of non-vaccine serotypes and nonencapsulated S.

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis.

While significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule-independent protection has been limited by serotype replacement along with disease caused by nonencapsulatedStreptococcus pneumoniae(NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis.

Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization.

Current vaccinations are effective against encapsulated strains of Streptococcus pneumoniae, but they do not protect against nonencapsulated Streptococcus pneumoniae (NESp), which is increasing in colonization and incidence of pneumococcal disease. Vaccination with pneumococcal proteins has been assessed for its ability to protect against pneumococcal disease, but several of these proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an NESp virulence factor, has not been assessed for immunogenic potential or host modulatory effects.

Differential bacterial gene expression during experimental pneumococcal endophthalmitis.

Streptococcus pneumoniae (pneumococcus) is a potential cause of bacterial endophthalmitis in humans that can result in ocular morbidity. We sought to identify pneumococcal genes that are differentially expressed during growth in the vitreous humor of the eye in an experimental endophthalmitis model. Microarray analysis was used to identify genes that were differentially expressed when pneumococci replicated in the vitreous of rabbit eyes as compared with bacteria grown in vitro in Todd Hewitt medium.

Nonencapsulated Streptococcus pneumoniae Cause Acute Otitis Media in the Chinchilla That Is Enhanced by Pneumococcal Surface Protein K.

Background: Use of the pneumococcal conjugate vaccine has led to serotype replacement of carriage and acute otitis media (AOM) pneumococcal isolates. Increases in nonencapsulated Streptococcus pneumoniae (NESp) isolates have also occurred, and there are increasing reports of NESp-associated disease. Disease prevalence and virulence factors of NESp isolates have not been studied.

Draft Genome Sequences of Five Multilocus Sequence Types of Nonencapsulated Streptococcus pneumoniae.

Nonencapsulated Streptococcus pneumoniae can colonize the human nasopharynx and cause conjunctivitis and otitis media. Different deletions in the capsular polysaccharide biosynthesis locus and different multilocus sequence types have been described for nonencapsulated strains. Draft genome sequences were generated to provide insight into the genomic diversity of these strains.

The cholesterol-dependent cytolysin pneumolysin from Streptococcus pneumoniae binds to lipid raft microdomains in human corneal epithelial cells.

Streptococcus pneumoniae (pneumococcus) is an opportunistic bacterial pathogen responsible for causing several human diseases including pneumonia, meningitis, and otitis media. Pneumococcus is also a major cause of human ocular infections and is commonly isolated in cases of bacterial keratitis, an infection of the cornea. The ocular pathology that occurs during pneumococcal keratitis is partly due to the actions of pneumolysin (Ply), a cholesterol-dependent cytolysin produced by pneumococcus.