Phase variable desialylation of host proteins that bind to <i>Streptococcus pneumoniae in vivo</i> and protect the airway

King, Samantha J.; Hippe, Karen R.; Gould, Jane M.; Bae, Deborah; Peterson, Scott N.; Cline, Robin T.; Fasching, Claudine E.; Janoff, Edward N.; Weiser, Jeffrey N.

doi:10.1111/j.1365-2958.2004.04252.x

Cited by 103 publications

(157 citation statements)

References 55 publications

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“…NanA has been shown to have a role in facilitating bacterial adherence by removing terminal sialic acid residues from glycoconjugates. Additionally, NanA is able to desialylate the cell surface of Neisseria meningitidis and Haemophilus influenzae (Ram et al, 1998;Shakhnovich et al, 2002), as well as antibacterial components of human airway secretions (King et al, 2004), potentially reducing pneumococcal clearance whilst promoting the clearance of competing bacteria. Our results provide further support for an important role for NanA in colonization of the nasopharynx by pneumococci.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of key pneumococcal virulence genes in vivo

2006

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Few studies have examined in vivo virulence gene expression in Streptococcus pneumoniae. In this study, expression of key pneumococcal virulence genes cbpA, pspA, ply, psaA, cps2A, piaA, nanA and spxB in the nasopharynx, lungs and bloodstream of mice was investigated, following intranasal challenge with the serotype 2 strain D39. Bacterial RNA was extracted, linearly amplified and assayed by real-time RT-PCR. At 72 h, cbpA mRNA was present at higher levels in the nasopharynx and lungs than in the blood. At this time-point, the mRNAs for PspA and PiaA were most abundant in the nasopharynx, whereas no significant difference in gene expression between niches was observed for ply, psaA and cps2A. Both nanA and spxB mRNAs were present in higher amounts in the nasopharynx than in the lungs or blood. These findings illustrate the dynamic nature of pneumococcal virulence gene expression in vivo. INTRODUCTIONStreptococcus pneumoniae (the pneumococcus) is a globally significant pathogen, responsible for invasive diseases such as pneumonia, bacteraemia and meningitis . The pneumococcus asymptomatically colonizes the nasopharynx, and such carriage is considered essential for subsequent development of disease in susceptible individuals (particularly infants, the elderly, and the immunocompromised). Disease commonly occurs following the aspiration of bacteria from the nasopharynx into the lungs, followed by colonization of the pulmonary epithelium and subsequent development of pneumonia. From this niche, the pneumococcus can invade the bloodstream and cause sepsis. Alternatively, bacteraemia can occur, following direct translocation from the nasopharyngeal epithelium into underlying tissues. The gene regulatory mechanisms involved in transition between, and survival in, these distinct host niches are poorly understood. This has primarily been due to technical difficulties in harvesting sufficient quantities of pneumococci from an animal model to perform accurate and quantitative RNA assays, particularly from niches such as the nasopharynx, in which bacteria exist asymptomatically and in low numbers.Several studies have been conducted in recent years comparing in vivo and in vitro pneumococcal gene expression. Orihuela et al. (2000) used Northern blotting to assess virulence gene mRNA levels in type 3 pneumococci grown in sealed dialysis bags implanted in the murine peritoneal cavity. In another study, differences in gene expression between virulent type 2 pneumococci harvested from the blood of mice infected intraperitoneally and those grown in serum broth were examined using semi-quantitative RT-PCR (Ogunniyi et al., 2002). More recently, in vivo studies have used microarray technology to quantitate S. pneumoniae transcript abundance in the blood of infected mice and the cerebrospinal fluid of infected rabbits (Orihuela et al., 2004b).The present work is the first to evaluate in vivo changes in pneumococcal gene expression during the natural progression of disease from colonization of the nasopharynx to invasion of the lungs...

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Section: Discussionmentioning

confidence: 99%

Differential expression of key pneumococcal virulence genes in vivo

2006

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“…Because terminal sialic acids protect these respiratory pathogens against complementmediated phagocytosis, desialylation of competitors may provide an advantage during colonization of host niches. Secondly, NanA has been shown to be implicated in desialylation of human proteins exhibiting sialic acid, including the secretory component, lactoferrin and IgA2 (King et al, 2004). These human proteins are pneumococcal host targets, and the removal of sialic acid may facilitate bacterial persistence in the respiratory tract.…”

Section: Biological Activities Of Unusually Cell-wallanchored Cholinementioning

confidence: 99%

Versatility of pneumococcal surface proteins

2006

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Surface-exposed proteins are key players during the infectious process of pathogenic bacteria. The cell surface of the Gram-positive human pathogen Streptococcus pneumoniae is decorated not only by typical Gram-positive surface proteins, but also by a family of proteins that recognizes the phosphorylcholine of the lipoteichoic and teichoic acids, namely the choline-binding proteins, and by non-classical surface proteins that lack a leader peptide and membrane-anchor motif. A comprehensive understanding of how microbial proteins subvert host immunity or host protein functions is a prerequisite for the development of novel therapeutic strategies to combat pneumococcal infections. This article reviews recent progress in the investigation of the versatility and sophistication of the virulence functions of surface-exposed pneumococcal proteins.

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“…Identification of phase variations was performed as described previously [22,13]. Briefly, colony morphology on the TSA+C plates was evaluated under a stereo-dissecting microscope equipped with double oblique, transmitted and adjustable-angle lights.…”

Section: Identification Of Phase Variationsmentioning

confidence: 99%

Interaction of pneumococcal phase variation and middle ear pressure/gas composition: An in vitro model of simulated otitis media

Li-Korotky¹,

Banks²,

Lo³

et al. 2008

Microbial Pathogenesis

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Streptococcus pneumoniae, a leading cause of otitis media (OM), undergoes spontaneous intra-strain variations in colony morphology. Transparent (T) variant is more efficient in colonizing the nasopharynx while the opaque (O) variant exhibits greater virulence during systemic infections. We hypothesized that changes in middle ear (ME) gas pressure/composition during Eustachian tube (ET) dysfunction and the treatment of that dysfunction, e.g., tympanostomy tube (TT) insertion, play a role in selecting the S. pneumonia variant that can efficiently colonize/infect the ME mucosa. Human ME epithelial cells were preconditioned for 24 hrs under one of three conditions that simulated 1) normal ME, 2) ME with ET obstruction (ETO) and 3) ME with TT; subsequently exposed to a dose (~10 7 CFU/ml) of either T or O variant of S. pneumoniae, and then incubated for 1 hr and 3 hrs. Under the simulated ETO and TT conditions, T variant exhibited a higher growth rate and greater epithelial adherence and killing than did O variants. Attachment of T variant to epithelial cells was documented by scanning electron microscopy. These results suggest that the T-variant is more highly adapted to various ME environments than the O-variants.

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Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway

Cited by 103 publications

References 55 publications

Differential expression of key pneumococcal virulence genes in vivo

Differential expression of key pneumococcal virulence genes in vivo

Versatility of pneumococcal surface proteins

Interaction of pneumococcal phase variation and middle ear pressure/gas composition: An in vitro model of simulated otitis media

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