In Vitro Activity of New Cephalosporins vs Streptococcus pneumoniae from the Canadian Bacterial Surveillance Network: 2008-2011.

Curr Microbiol. 2014 Jul 15. [Epub ahead of print]

In Vitro Activity of New Cephalosporins vs Streptococcus pneumoniae from the Canadian Bacterial Surveillance Network: 2008-2011.

Green K1, McGeer A, Rudnick W, Pong-Porter S, Patel SN, Low DE; The Canadian Bacterial Surveillance Network (CBSN).

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Abstract

Between 2008 and 2011, 6,895 Streptococcus pneumoniae isolates were submitted to the Canadian Bacterial Surveillance Network and underwent in vitro susceptibility testing. Fifteen percent of S. pneumoniae isolates were collected from pediatric patients (0-15 years old), 48.6 % of isolates were collected from adults between 16 and 64 years of age, and 36.1 % from adults aged ≥65 years; age data were not available for 11 patients. Forty-five percent of S. pneumoniae isolates were recovered from sterile specimens, and 55 % of isolates were from nonsterile specimens. Overall, 0.4 % of isolates were resistant to penicillin, 0.4 % to ceftriaxone, 3 % to amoxicillin, 25 % to erythromycin, and 13 % to trimethoprim/sulfamethoxazole; 6.6 % of isolates were multidrug resistant (MDR). Among MDR isolates, resistance rates exceeded 95 % for erythromycin, tetracycline, and trimethoprim/sulfamethoxazole. The MIC90 of cethromycin, ceftaroline, and ceftobiprole against MDR isolates were 0.12, 0.25, and 1 mg/L, respectively. Ceftaroline, the active form of the prodrug ceftaroline fosamil, exhibited potent in vitro activity against the tested S. pneumoniae including all 456 multidrug-resistant strains. No ceftaroline-resistant isolates were identified.

PMID: 25023636 [PubMed - as supplied by publisher]

Determination of native capsular polysaccharide structures of Streptococcus pneumoniae serotypes 39, 42, and 47F and comparison to genetically or serologically related strains.

Carbohydr Res. 2014 Aug 18;395:38-46. doi: 10.1016/j.carres.2014.06.018. Epub 2014 Jun 26.

Determination of native capsular polysaccharide structures of Streptococcus pneumoniae serotypes 39, 42, and 47F and comparison to genetically or serologically related strains.

Petersen BO1, Meier S2, Paulsen BS3, Redondo AR4, Skovsted IC4.

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Abstract

The diversity of capsular polysaccharides of the bacterial pathogen Streptococcus pneumoniae leads to at least 91 different serotypes. While the genetic loci for capsular biosynthesis have been characterized for all serotypes, the determination of resultant polysaccharide structures remains incomplete. Here, we report the chemical structures of the capsular polysaccharides of serotypes 39, 42, and 47F from the genetic cluster 4, and discuss the structures in the context of structures from serologically and genetically related serotypes. Antigenic determinants can be approximated in this manner. The structure of the serotype 39 capsular polysaccharide is and has identical composition to the capsular polysaccharide 10A, but two different linkages. The serotype 42 structure closely resembles the genetically related serotype 35A, which does not contain residue A. The structure of the serotype 47F capsular polysaccharide is somewhat different from a recently determined structure from the same serogroup, while containing a structural motif that is reflected in serotype 35A and 42 capsular polysaccharide structures, thus explaining the cross-reactivity of serotype 47F with the typing serum 35a.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Capsular polysaccharide; NMR; Serotype 39; Serotype 42; Serotype 47F; Streptococcus pneumoniae

PMID: 25036733 [PubMed - in process]

Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator binding protein.

Mol Immunol. 2014 Jul 18;62(1):249-264. doi: 10.1016/j.molimm.2014.06.029. [Epub ahead of print]

Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator binding protein.

Mohan S1, Hertweck C2, Dudda A1, Hammerschmidt S3, Skerka C1, Hallström T1, Zipfel PF4.

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Abstract

Streptococcus pneumoniae is a Gram-positive bacterium, causing acute sinusitis, otitis media, and severe diseases such as pneumonia, bacteraemia, meningitis and sepsis. Here we identify elongation factor Tu (Tuf) as a new Factor H binding protein of S. pneumoniae. The surface protein PspC which also binds a series of other human immune inhibitors, was the first identified pneumococcal Factor H binding protein of S. pneumoniae. Pneumococcal Tuf, a 55kDa pneumococcal moonlighting protein which is displayed on the surface of pneumococci, is also located in the cytoplasm and is detected in the culture supernatant. Tuf binds the human complement inhibitors Factor H, FHL-1, CFHR1 and also the proenzyme plasminogen. Factor H and FHL-1 bound to Tuf, retain their complement regulatory activities. Similarly, plasminogen bound to Tuf was accessible for the activator uPA and activated plasmin cleaved the synthetic chromogenic substrate S-2251 as well as the natural substrates fibrinogen and the complement proteins C3 and C3b. Taken together, Tuf of S. pneumoniae is a new multi-functional bacterial virulence factor that helps the pathogen in complement escape and likely also in ECM degradation.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Complement; ECM; Factor H; Plasminogen; Tuf

PMID: 25046156 [PubMed - as supplied by publisher]

Sinefungin, a Natural Nucleoside Analogue of S-Adenosylmethionine, Inhibits Streptococcus pneumoniae Biofilm Growth.

Biomed Res Int. 2014;2014:156987. doi: 10.1155/2014/156987. Epub 2014 Jun 23.

Sinefungin, a Natural Nucleoside Analogue of S-Adenosylmethionine, Inhibits Streptococcus pneumoniae Biofilm Growth.

Yadav MK1, Park SW2, Chae SW1, Song JJ1.

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Abstract

Pneumococcal colonization and disease is often associated with biofilm formation, in which the bacteria exhibit elevated resistance both to antibiotics and to host defense systems, often resulting in infections that are persistent and difficult to treat. We evaluated the effect of sinefungin, a nucleoside analogue of S-adenosylmethionine, on pneumococcal in vitro biofilm formation and in vivo colonization. Sinefungin is bacteriostatic to pneumococci and significantly decreased biofilm growth and inhibited proliferation and structure of actively growing biofilms but did not alter growth or the matrix structure of established biofilms. Sinefungin significantly reduced pneumococcal colonization in rat middle ear. The quorum sensing molecule (autoinducer-2) production was significantly reduced by 92% in sinefungin treated samples. The luxS, pfs, and speE genes were downregulated in biofilms grown in the presence of sinefungin. This study shows that sinefungin inhibits pneumococcal biofilm growth in vitro and colonization in vivo, decreases AI-2 production, and downregulates luxS, pfs, and speE gene expressions. Therefore, the S-adenosylmethionine (SAM) inhibitors could be used as lead compounds for the development of novel antibiofilm agents against pneumococci.

PMID: 25050323 [PubMed - in process] PMCID: PMC4094849 Free PMC Article

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Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.

Biometals. 2014 Jul 23. [Epub ahead of print]

Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.

León-Sicairos N1, Angulo-Zamudio UA, Vidal JE, López-Torres CA, Bolscher JG, Nazmi K, Reyes-Cortes R, Reyes-López M, de la Garza M, Canizalez-Román A.

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Abstract

Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million child deaths annually. Pneumococcus causes infections such as pneumonia, otitis media, meningitis, and sepsis. The human immune system includes antibacterial peptides and proteins such as lactoferrin (LF), but its activity against pneumococcus is not fully understood. The aim of this work was to evaluate the bactericidal effect of bovine lactoferrin (bLF) and the synthetic LF-peptides lactoferricin (LFcin17-30), lactoferrampin (LFampin265-284), and LFchimera against S. pneumoniae planktonic cells. The mechanism of damage was also investigated, as well as the impact of these peptides on the transcription levels of genes known to encode important virulence factors. S. pneumoniae planktonic cells were treated with bLF, LFcin17-30, LFampin265-284 and LFchimera at different time points. The viability of treated planktonic cells was assessed by dilution and plating (in CFU/ml). The interaction between LF and LF-peptides coupled to fluorescein was visualized using a confocal microscope and flow cytometry, whereas the damage at structural levels was observed by electron microscopy. Damage to bacterial membranes was further evaluated by membrane permeabilization by use of propidium iodide and flow cytometry, and finally, the expression of pneumococcal genes was evaluated by qRT-PCR. bLF and LFchimera were the best bactericidal agents. bLF and peptides interacted with bacteria causing changes in the shape and size of the cell and membrane permeabilization. Moreover, the luxS gene was down-regulated in bacteria treated with LF. In conclusion, LF and LFchimera have a bactericidal effect, and LF down-regulates genes involved in the pathogenicity of pneumococcus, thus demonstrating potential as new agents for the treatment of pneumococcal infections.

PMID: 25053107 [PubMed - as supplied by publisher]

Parallel Evolution of Streptococcus pneumoniae and Streptococcus mitis to Pathogenic and Mutualistic Lifestyles.

MBio. 2014 Jul 22;5(4). pii: e01490-14. doi: 10.1128/mBio.01490-14.

Parallel Evolution of Streptococcus pneumoniae and Streptococcus mitis to Pathogenic and Mutualistic Lifestyles.

Kilian M1, Riley DR2, Jensen A3, Brüggemann H3, Tettelin H2.

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Abstract

The bacterium Streptococcus pneumoniae is one of the leading causes of fatal infections affecting humans. Intriguingly, phylogenetic analysis shows that the species constitutes one evolutionary lineage in a cluster of the otherwise commensal Streptococcus mitis strains, with which humans live in harmony. In a comparative analysis of 35 genomes, including phylogenetic analyses of all predicted genes, we have shown that the pathogenic pneumococcus has evolved into a master of genomic flexibility while lineages that evolved into the nonpathogenic S. mitis secured harmonious coexistence with their host by stabilizing an approximately 15%-reduced genome devoid of many virulence genes. Our data further provide evidence that interspecies gene transfer between S. pneumoniae and S. mitis occurs in a unidirectional manner, i.e., from S. mitis to S. pneumoniae. Import of genes from S. mitis and other mitis, anginosus, and salivarius group streptococci ensured allelic replacements and antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae. Our study explains how the unique structural diversity of the pneumococcal capsule emerged and conceivably will continue to increase and reveals a striking example of the fragile border between the commensal and pathogenic lifestyles. While genomic plasticity enabling quick adaptation to environmental stress is a necessity for the pathogenic streptococci, the commensal lifestyle benefits from stability.

IMPORTANCE:

One of the leading causes of fatal infections affecting humans, Streptococcus pneumoniae, and the commensal Streptococcus mitis are closely related obligate symbionts associated with hominids. Faced with a shortage of accessible hosts, the two opposing lifestyles evolved in parallel. We have shown that the nonpathogenic S. mitis secured harmonious coexistence with its host by stabilizing a reduced genome devoid of many virulence genes. Meanwhile, the pathogenic pneumococcus evolved into a master of genomic flexibility and imports genes from S. mitis and other related streptococci. This process ensured antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae, which conceivably will continue to increase and present a challenge to disease prevention.

Copyright © 2014 Kilian et al.

PMID: 25053789 [PubMed - in process] Free full text

Direct Streptococcus pneumoniae real-time PCR serotyping from pediatric parapneumonic effusions.

BMC Pediatr. 2014 Jul 24;14(1):189.

Direct Streptococcus pneumoniae real-time PCR serotyping from pediatric parapneumonic effusions.

Slinger R1, Hyde L, Moldovan I, Chan F, Pernica JM.

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Abstract

BACKGROUND:

To determine the serotypes of Streptococcus pneumoniae responsible for pneumonia complicated by parapneumonic effusion in children, we performed real-time PCR based pneumococcal "serotyping" directly on parapneumonic fluid samples.

METHODS:

Specimens were collected at two children's hospitals in Ontario, Canada from 2009 to 2011. Samples in which S. pneumoniae was detected by PCR were tested with serotype-specific 5'exonuclease PCR assays for the 13 serotypes contained in the 13-serotype pneumococcal vaccine.

RESULTS:

Thirty-five S. pneumoniae PCR-positive pleural samples were studied. Pneumococcal serotyping PCR assays were positive for 34 of 35 (97%). Serotype 3 was detected most frequently, in 19/35 (54%), followed by serotype 19A in 9/35 (26%), serotype 7 F/A in 4/35 (11%), serotype 1 in 1/35 (3%), and serotype 6A also in 1/35 (3%).

CONCLUSIONS:

PCR testing demonstrated that the vast majority (97%) of S. pneumoniae parapneumonic effusions were caused by serotypes present in the 13-serotype vaccine that were not present in the original 7 serotype vaccine. This suggests that use of the 13-serotype vaccine could potentially prevent many S. pneumoniae pneumonias complicated by parapneumonic effusion in our region, provided serotype replacement does not occur.

PMID: 25060939 [PubMed - as supplied by publisher] PMCID: PMC4118202 Free PMC Article

Overlapping Functionality of the Pht Proteins in Zinc Homeostasis of Streptococcus pneumoniae.

Infect Immun. 2014 Jul 28. pii: IAI.02155-14. [Epub ahead of print]

Overlapping Functionality of the Pht Proteins in Zinc Homeostasis of Streptococcus pneumoniae.

Plumptre CD1, Hughes CE1, Harvey RM1, Eijkelkamp BA1, McDevitt CA1, Paton JC2.

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Abstract

Streptococcus pneumoniae is a globally significant pathogen that causes a range of diseases including pneumonia, sepsis, meningitis and otitis media. Its ability to do so depends upon the acquisition of nutrients from its environment, including transition metal ions such as zinc. The pneumococcus employs a number of surface proteins to achieve this, amongst which are four highly similar polyhistidine triad (Pht) proteins. It has previously been established that these proteins collectively aid in the delivery of zinc to the ABC transporter substrate binding protein AdcAII. Here we have investigated the contributions of each individual Pht protein to pneumococcal zinc homeostasis by analyzing mutant strains expressing only one of the four pht genes. Under conditions of low zinc availability, each of these mutants showed superior growth and zinc accumulation profiles relative to a mutant strain lacking all four genes, indicating that any of the four Pht proteins are able to facilitate delivery of zinc to AdcAII. However, optimal growth and zinc accumulation in vitro and pneumococcal survival and proliferation in vivo required production of all four Pht proteins, indicating that, despite their overlapping functionality, the proteins are not dispensable without incurring a fitness cost. We also show that surface attached forms of the Pht proteins are required for zinc recruitment, and that they do not contribute to defence against extracellular zinc stress.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID: 25069983 [PubMed - as supplied by publisher]

Tn5253 family integrative and conjugative elements carrying mef(I) and catQ determinants in Streptococcus pneumoniae and Streptococcus pyogenes.

Antimicrob Agents Chemother. 2014 Jul 28. pii: AAC.03638-14. [Epub ahead of print]

Tn5253 family integrative and conjugative elements carrying mef(I) and catQ determinants in Streptococcus pneumoniae and Streptococcus pyogenes.

Mingoia M1, Morici E1, Morroni G1, Giovanetti E2, Del Grosso M3, Pantosti A3, Varaldo PE4.

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Abstract

The linkage between the macrolide efflux gene mef(I) and the chloramphenicol inactivation gene catQ was first described in Streptococcus pneumoniae (strain Spn529), where the two genes are located in a module designated IQ element. Subsequently, two different, defective IQ elements were detected in Streptococcus pyogenes (strains Spy029 and Spy005). The genetic elements carrying the three IQ elements were characterized and all were found to be Tn5253 family integrative and conjugative elements (ICEs). The ICE from S. pneumoniae (ICESpn529IQ) was sequenced, whereas those from S. pyogenes (ICESpy029IQ and ICESpy005IQ, the first Tn5253-like ICEs reported in this species) were characterized by PCR mapping, partial sequencing and restriction analysis. ICESpn529IQ and ICESpy029IQ were found to share the intSp 23FST81 integrase gene and an identical Tn916 fragment, whereas ICESpy005IQ had int5252 and lacked Tn916. All three ICEs lacked the linearized pC194 plasmid that is usually associated to Tn5253-like ICEs, and all displayed a single copy of a toxin-antitoxin operon that is typically contained in the direct repeats flanking the excisable pC194 region when the latter is present. Two different insertion sites of the IQ elements were detected, one in ICESpn529IQ and ICESpy029IQ and another in ICESpy005IQ. The chromosomal integration of the three ICEs was site-specific, depending on the integrase (intSp 23FST81 or int5252). Only ICESpy005IQ was excised in circular form and transferred by conjugation. By transformation, mef(I) and catQ were cotransferred at high frequency from S. pyogenes Spy005, and at very low frequencies from S. pneumoniae Spn529 and S. pyogenes Spy029.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID: 25070090 [PubMed - as supplied by publisher]

Carriage of Streptococcus pneumoniae and Other Respiratory Bacterial Pathogens in Low and Lower-Middle Income Countries: A Systematic Review and Meta-Analysis.

PLoS One. 2014 Aug 1;9(8):e103293. doi: 10.1371/journal.pone.0103293. eCollection 2014.

Carriage of Streptococcus pneumoniae and Other Respiratory Bacterial Pathogens in Low and Lower-Middle Income Countries: A Systematic Review and Meta-Analysis.

Adegbola RA1, DeAntonio R1, Hill PC2, Roca A3, Usuf E3, Hoet B1, Greenwood BM4.

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Abstract

BACKGROUND:

Infection with Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide, especially in low income countries where pneumococcal conjugate vaccines (PCVs) are still underused. In countries where PCVs have been introduced, much of their efficacy has resulted from their impact on nasopharyngeal carriage in vaccinated children. Understanding the epidemiology of carriage for S. pneumoniae and other common respiratory bacteria in developing countries is crucial for implementing appropriate vaccination strategies and evaluating their impact.

METHODS AND FINDINGS:

We have systematically reviewed published studies reporting nasopharyngeal or oropharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Neisseria meningitidis in children and adults in low and lower-middle income countries. Studies reporting pneumococcal carriage for healthy children <5 years of age were selected for a meta-analysis. The prevalences of carriage for S. pneumoniae, H. influenzae, and M. catarrhalis were generally higher in low income than in lower-middle income countries and were higher in young children than in adults. The prevalence of S. aureus was high in neonates. Meta-analysis of data from young children before the introduction of PCVs showed a pooled prevalence estimate of 64.8% (95% confidence interval, 49.8%-76.1%) in low income countries and 47.8% (95% confidence interval, 44.7%-50.8%) in lower-middle income countries. The most frequent serotypes were 6A, 6B, 19A, 19F, and 23F.

CONCLUSIONS:

In low and lower-middle income countries, pneumococcal carriage is frequent, especially in children, and the spectrum of serotypes is wide. However, because data are limited, additional studies are needed to adequately assess the impact of PCV introduction on carriage of respiratory bacteria in these countries.

PMID: 25084351 [PubMed - in process] PMCID: PMC4118866 Free PMC Article

Inspecting the potential physiological and biomedical value of 44 conserved uncharacterised proteins of Streptococcus pneumoniae.

BMC Genomics. 2014 Aug 5;15(1):652. [Epub ahead of print]

Inspecting the potential physiological and biomedical value of 44 conserved uncharacterised proteins of Streptococcus pneumoniae.

Martín-Galiano AJ, Yuste J, Cercenado MI, de la Campa AG.

Abstract

BACKGROUND:

The major Gram-positive coccoid pathogens cause similar invasive diseases and show high rates of antimicrobial resistance. Uncharacterised proteins shared by these organisms may be involved in virulence or be targets for antimicrobial therapy.

RESULTS:

Forty four uncharacterised proteins from Streptococcus pneumoniae with homologues in Enterococcus faecalis and/or Staphylococcus aureus were selected for analysis. These proteins showed differences in terms of sequence conservation and number of interacting partners. Twenty eight of these proteins were monodomain proteins and 16 were modular, involving domain combinations and, in many cases, predicted unstructured regions. The genes coding for four of these 44 proteins were essential. Genomic and structural studies showed one of the four essential genes to code for a promising antibacterial target. The strongest impact of gene removal was on monodomain proteins showing high sequence conservation and/or interactions with many other proteins. Eleven out of 40 knockouts (one for each gene) showed growth delay and 10 knockouts presented a chaining phenotype. Five of these chaining mutants showed a lack of putative DNA-binding proteins. This suggest this phenotype results from a loss of overall transcription regulation. Five knockouts showed defective autolysis in response to penicillin and vancomycin, and attenuated virulence in an animal model of sepsis.

CONCLUSIONS:

Uncharacterised proteins make up a reservoir of polypeptides of different physiological importance and biomedical potential. A promising antibacterial target was identified. Five of the 44 examined proteins seemed to be virulence factors.

PMID: 25096389 [PubMed - as supplied by publisher] Free full text

Pneumonia and Purulent Pericarditis Caused by Streptococcus pneumoniae: An Uncommon Association in the Antibiotic Era.

Pediatr Emerg Care. 2014 Aug;30(8):552-4. doi: 10.1097/PEC.0000000000000186.

Pneumonia and Purulent Pericarditis Caused by Streptococcus pneumoniae: An Uncommon Association in the Antibiotic Era.

Flores-González JC1, Rubio-Quiñones F, Hernández-González A, Rodríguez-González M, Blanca-García JA, Lechuga-Sancho AM, Quintero-Otero S.

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Abstract

Bacterial pericarditis in children has become a rare entity in the modern antibiotic era. The most common pathogen is Staphylococcus aureus, being Streptococcus pneumoniae an exceptional cause. We present 2 children, who were diagnosed of pneumonia complicated with a pleural effusion that developed a purulent pericarditis with signs of cardiac tamponade. One of them had received 4 doses of the 7-valent conjugated pneumococcal vaccine. Systemic antibiotics and pericardial and pleural drainages were used. Pneumococcal antigens were positive in pleural and pericardial fluids in both cases, and S. pneumoniae was isolated from pleural effusion in one of them. Both children fully recovered, and none of them developed constrictive pericarditis, although 1 case presented a transient secondary left ventricular dysfunction. Routine immunization with 10- and 13-valent vaccines including a wider range of serotypes should further decrease the already low incidence.

PMID: 25098798 [PubMed - in process]

Pbp2x Localizes Separately from Pbp2b and Other Peptidoglycan Synthesis Proteins during Later Stages of Cell Division of Streptococcus pneumoniae D39.

Mol Microbiol. 2014 Aug 6. doi: 10.1111/mmi.12745. [Epub ahead of print]

Pbp2x Localizes Separately from Pbp2b and Other Peptidoglycan Synthesis Proteins during Later Stages of Cell Division of Streptococcus pneumoniae D39.

Tsui HC1, Boersma MJ, Vella SA, Kocaoglu O, Kuru E, Peceny JK, Carlson EE, VanNeuwenhze MS, Brun YV, Shaw SL, Winkler ME.

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Abstract

The relative localization patterns of class B penicillin-binding proteins Pbp2x and Pbp2b were used as positional indicators of septal and peripheral (side-wall-like) peptidoglycan (PG) synthesis, respectively, in the midcell regions of Streptococcus pneumoniae cells at different stages of division. We confirm that Pbp2x and Pbp2b are essential in the strain D39 genetic background, which differs from that of laboratory strains. We show that Pbp2b, like Pbp2x and class A Pbp1a, follows a different localization pattern than FtsZ and remains at division septa after FtsZ reappears at the equators of daughter cells. Pulse-experiments with fluorescent D-amino acids (FDAAs) were performed in wild-type cells and in cells in which Pbp2x activity was preferentially inhibited by methicillin or Pbp2x amount was depleted. These experiments show that Pbp2x activity separates from that of other PBPs to the centers of constricting septa in mid-to-late divisional cells resolved by high-resolution 3D-SIM microscopy. Dual-protein and protein-fluorescent vancomycin 2D and 3D-SIM immunofluorescence microscopy (IFM) of cells at different division stages corroborate that Pbp2x separates to the centers of septa surrounded by an adjacent constricting ring containing Pbp2b, Pbp1a, and regulators, StkP and MreC. The separate localization of Pbp2x suggests distinctive roles in completing septal PG synthesis and remodeling.

This article is protected by copyright. All rights reserved.

KEYWORDS:

MreC; Pbp1a; Penicillin-binding proteins (PBPs); StkP; class B PBPs; peptidoglycan biosynthesis

PMID: 25099088 [PubMed - as supplied by publisher]

Conformational analysis of the Streptococcus pneumoniae hyaluronate lyase and characterization of its hyaluronan-specific carbohydrate-binding module.

J Biol Chem. 2014 Aug 6. pii: jbc.M114.578435. [Epub ahead of print]

Conformational analysis of the Streptococcus pneumoniae hyaluronate lyase and characterization of its hyaluronan-specific carbohydrate-binding module.

Suits MD1, Pluvinage B2, Law A2, Liu Y3, Palma AS3, Chai W3, Feizi T4, Boraston AB5.

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Abstract

For a subset of pathogenic microorganisms, including Streptococcus pneumoniae, the recognition and degradation of host hyaluronan contributes to bacterial spreading through the extracellular matrix and enhancing access to host-cell surfaces. The hyaluronate lyase, Hyl, presented on the surface of S. pneumoniae performs this role. Using glycan microarray screening, affinity electrophoresis, and isothermal titration calorimetry we show that the N-terminal module of Hyl is a hyaluronan-specific carbohydrate-binding module (CBM) and the founding member of CBM family 70. The 1.2 Å resolution X-ray crystal structure of CBM70 revealed it to have a β-sandwich fold similar to other CBMs. The electrostatic properties of the binding site, which was identified by site-directed mutagenesis, are distinct from other CBMs and complementary to its acidic ligand, hyaluronan. Dynamic light scattering and solution small-angle X-ray scattering (SAXS) revealed the full-length Hyl protein to exist as a monomer-dimer mixture in solution. Through a detailed analysis of the SAXS data we report the pseudo-atomic solution structures of the monomer and dimer forms of the full-length multimodular Hyl.

Copyright © 2014, The American Society for Biochemistry and Molecular Biology.

KEYWORDS:

Streptococcus; carbohydrate; carbohydrate processing; carbohydrate-binding protein; crystallography; glycobiology; hyaluronan; hyaluronate lyase; small-angle X-ray scattering (SAXS)

PMID: 25100731 [PubMed - as supplied by publisher] Free full text

Co-infection with Streptococcus pneumoniae modulates the B cell response to influenza virus.

J Virol. 2014 Aug 6. pii: JVI.01833-14. [Epub ahead of print]

Co-infection with Streptococcus pneumoniae modulates the B cell response to influenza virus.

Wolf AI1, Strauman MC1, Mozdzanowska K1, Whittle JR2, Williams KL1, Sharpe AH3, Weiser JN4, Caton AJ1, Hensley SE1, Erikson J5.

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Abstract

Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae (Sp) and are the basis of effective vaccines. Sequential or overlapping co-infections with both pathogens are common, yet the impact of co-infection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in IAV-Sp co-infected mice and that this response differs depending on the order of pathogen exposure. In mice exposed to Sp prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4+ T follicular helper (TFH) cell numbers. In contrast, secondary Sp infection exaggerates early anti-viral antibody secreting cell formation, and at later times GCs, TFH cells and anti-viral serum IgG are elevated. Mice exposed to Sp prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs, and exhibit reduced anti-viral serum IgG with diminished virus-neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective anti-viral Abs and may partially explain the differential susceptibility and disease outcomes to IAV infection in humans.

IMPORTANCE:

Respiratory tract co-infections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how Sp co-infection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID: 25100838 [PubMed - as supplied by publisher]