Specific growth conditions induce a Streptococcus pneumoniae non-mucoidal, small colony variant and determine the outcome of its co-culture with Haemophilus influenzae.

Haemophilus influenzae and Streptococcus pneumoniae are known aetiologic agents of chronic otitis media, frequently as a multispecies infection. In this study, we show that the outcome of H. influenzae/S.

In vitro characterization and identification of potential substrates of a low molecular weight protein tyrosine phosphatase in Streptococcus pneumoniae.

Streptococcus pneumoniae is a major human pathogen responsible for significant mortality and morbidity worldwide. Within the annotated genome of the pneumococcus lies a previously uncharacterized protein tyrosine phosphatase which shows homology to low molecular weight protein tyrosine phosphatases (LMWPTPs). LMWPTPs modulate many processes critical for the pathogenicity of a number of bacteria including capsular polysaccharide biosynthesis, stress response and persistence in host macrophages.

Role of Streptococcus pneumoniae OM001 operon in capsular polysaccharide production, virulence and survival in human saliva.

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in all ages worldwide, and with ever-increasing antibiotic resistance, the understanding of its pathogenesis and spread is as important as ever. Recently, we reported the presence of a Low Molecular Weight Tyrosine Phosphatase (LMWPTP) Spd1837 in the pneumococcus. This protein is encoded in an operon, OM001 with two other genes, with previous work implicating this operon as important for pneumococcal virulence.

Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents.

CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn, in the active site.

Unprecedented Abundance of Protein Tyrosine Phosphorylation Modulates Shigella flexneri Virulence.

Evidence is accumulating that protein tyrosine phosphorylation plays a crucial role in the ability of important human bacterial pathogens to cause disease. While most works have concentrated on its role in the regulation of a major bacterial virulence factor, the polysaccharide capsule, recent studies have suggested a much broader role for this post-translational modification. This prompted us to investigate protein tyrosine phosphorylation in the human pathogen Shigella flexneri.

Topology of Streptococcus pneumoniae CpsC, a polysaccharide copolymerase and bacterial protein tyrosine kinase adaptor protein.

In Gram-positive bacteria, tyrosine kinases are split into two proteins, the cytoplasmic tyrosine kinase and a transmembrane adaptor protein. In Streptococcus pneumoniae, this transmembrane adaptor is CpsC, with the C terminus of CpsC critical for interaction and subsequent tyrosine kinase activity of CpsD. Topology predictions suggest that CpsC has two transmembrane domains, with the N and C termini present in the cytoplasm.

Tyrosine phosphorylation enhances activity of pneumococcal autolysin LytA.

Tyrosine phosphorylation has long been recognized as a crucial post-translational regulatory mechanism in eukaryotes. However, only in the past decade has recognition been given to the crucial importance of bacterial tyrosine phosphorylation as an important regulatory feature of pathogenesis. This study describes the effect of tyrosine phosphorylation on the activity of a major virulence factor of the pneumococcus, the autolysin LytA, and a possible connection to the Streptococcus pneumoniae capsule synthesis regulatory proteins (CpsB, CpsC and CpsD).

The role of bacterial protein tyrosine phosphatases in the regulation of the biosynthesis of secreted polysaccharides.

Significance: Tyrosine phosphorylation and associated protein tyrosine phosphatases are gaining prominence as critical mechanisms in the regulation of fundamental processes in a wide variety of bacteria. In particular, these phosphatases have been associated with the control of the biosynthesis of capsular polysaccharides and extracellular polysaccharides, critically important virulence factors for bacteria.

Recent Advances: Deletion and overexpression of the phosphatases result in altered polysaccharide biosynthesis in a range of bacteria.

Dual inhibition of DNA polymerase PolC and protein tyrosine phosphatase CpsB uncovers a novel antibiotic target.

Increasing antibiotic resistance is making the identification of novel antimicrobial targets critical. Recently, we discovered an inhibitor of protein tyrosine phosphatase CpsB, fascioquinol E (FQE), which unexpectedly inhibited the growth of Gram-positive pathogens. CpsB is a member of the polymerase and histidinol phosphate phosphatase (PHP) domain family.

Chemical inhibition of bacterial protein tyrosine phosphatase suppresses capsule production.

Capsule polysaccharide is a major virulence factor for a wide range of bacterial pathogens, including Streptococcus pneumoniae. The biosynthesis of Wzy-dependent capsules in both gram-negative and -positive bacteria is regulated by a system involving a protein tyrosine phosphatase (PTP) and a protein tyrosine kinase. However, how the system functions is still controversial.

Three surface exoglycosidases from Streptococcus pneumoniae, NanA, BgaA, and StrH, promote resistance to opsonophagocytic killing by human neutrophils.

Streptococcus pneumoniae (the pneumococcus) is a major human pathogen and a leading cause of inflammatory infections such as pneumonia and otitis media. An important mechanism for host defense against S. pneumoniae is opsonophagocytic killing by neutrophils.

Human neutrophils kill Streptococcus pneumoniae via serine proteases.

Neutrophils, or polymorphonuclear leukocytes, comprise a crucial component of innate immunity, controlling bacterial and fungal infection through a combination of both oxidative and nonoxidative mechanisms. Indeed, neutrophils are believed to play an important role in controlling infection caused by the major human pathogen Streptococcus pneumoniae. However, the method by which neutrophils kill the pneumococcus as well as other Gram-positive bacteria, is not fully understood.

Resistance to mucosal lysozyme compensates for the fitness deficit of peptidoglycan modifications by Streptococcus pneumoniae.

The abundance of lysozyme on mucosal surfaces suggests that successful colonizers must be able to evade its antimicrobial effects. Lysozyme has a muramidase activity that hydrolyzes bacterial peptidoglycan and a non-muramidase activity attributable to its function as a cationic antimicrobial peptide. Two enzymes (PgdA, a N-acetylglucosamine deacetylase, and Adr, an O-acetyl transferase) that modify different sites on the peptidoglycan of Streptococcus pneumoniae have been implicated in its resistance to lysozyme in vitro.

Neutrophil-toxin interactions promote antigen delivery and mucosal clearance of Streptococcus pneumoniae.

Delivery of Ag to inductive sites, such as nasal-associated lymphoid tissue (NALT) or GALT, is thought to promote mucosal immunity. Host and microbial factors that contribute to this process were investigated during model murine airway colonization by the pathogen Streptococcus pneumoniae. Colonization led to the deposition of released bacterial capsular Ag in the NALT in a manner consistent with trafficking through M cells.

The pneumococcal two-component signal transduction system RR/HK06 regulates CbpA and PspA by two distinct mechanisms.

We have previously shown that CbpA, a major pneumococcal virulence factor, is regulated by the two-component signal transduction system RR/HK06 (A. J. Standish, U.

Albomycin is an effective antibiotic, as exemplified with Yersinia enterocolitica and Streptococcus pneumoniae.

Albomycin belongs to the class of sideromycins, compounds composed of iron carriers linked to antibiotic moieties. Albomycin was found to be active against bacteria that have a functional ferric hydroxamate transport system meaning that bacteria will actively transport albomycin until they die. We examined the activity spectrum of albomycin for bacterial pathogens and found that Enterobacteriaceae except species of Proteus and Morganella were sensitive.

The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae.

Streptococcus pneumoniae encounters a number of environmental niches in the body, including the nasopharynx, lungs, blood, middle ear, and brain. Recent studies have identified 13 putative two-component signal-transduction systems in S. pneumoniae, which are likely to be important for gene regulation in response to external stimuli.