Effect of Zinc Supplementation on Serological Response to Vaccination Against Streptococcus Pneumoniae in Patients Undergoing Chemotherapy for Colorectal Cancer.

Nutr Cancer. 2015 Jul 2:1-7. [Epub ahead of print]

Effect of Zinc Supplementation on Serological Response to Vaccination Against Streptococcus Pneumoniae in Patients Undergoing Chemotherapy for Colorectal Cancer.

Bitu Moreno Braga C1, Kinney Ferreira de Miranda Santos I, Palmeira P, Maris Peria F, Miranda de Figueiredo Ribeiro S, Zangiacomi Martinez E, Joaquim Ribeiro da Rocha J, Freire de Carvalho da Cunha S.

Author information

Abstract

The aim of the study was to evaluate the effect of zinc supplementation on the antibody titer and the 23-valent pneumococcal seroconversion after vaccination in patients undergoing chemotherapy for colorectal cancer. The study included 25 patients undergoing postsurgery chemotherapy for colorectal adenocarcinoma (chemo group). Subjects were assessed in the perioperative period (prevaccination), before chemotherapy (4th wk) and after 3 cycles of chemotherapy (16th wk). Thirty-two healthy volunteers (control group) were included in the study. Participants received the 23-valent pneumococcal conjugate vaccine, and capsules containing zinc (Zn) sulfate (70 mg daily) or identical placebo capsules (containing wheat starch with no added Zn) for 16 wk and were randomly allocated on one of the following groups: chemo-Zn (n = 10), chemo-placebo (n = 15), control-Zn (n = 21), and control-placebo (n = 11). The antipneumococcal antibody titer against 6 polysaccharides was analyzed by ELISA and compared using linear mixed models. The seroconversion rate was compared using Fisher's exact test. An immune response to the vaccination against pneumococcus was observed in all participants. In the 16th wk, the polysaccharide 6 concentration was lower in the chemo-Zn group [2.96 (1.74-5.03) μg/mL] compared with the Chemo-Placebo group [10.75 (5.37-21.54) μg/mL] and the seroconversion rate was lower in the chemo-placebo (36%) compared with the control-placebo (85%) (P = 0.027). Zinc supplementation did not change the antibody titer after vaccination. However, the lower seroconversion rate observed in the chemo-placebo suggests an influence of zinc in the vaccinal protection.

PMID: 26134076 [PubMed - as supplied by publisher]

Humoral immune responses to Streptococcus pneumoniae in the setting of HIV-1 infection.

Vaccine. 2015 Jun 30. pii: S0264-410X(15)00878-6. doi: 10.1016/j.vaccine.2015.06.077. [Epub ahead of print]

Humoral immune responses to Streptococcus pneumoniae in the setting of HIV-1 infection.

Zhang L1, Li Z1, Wan Z2, Kilby A3, Kilby JM4, Jiang W5.

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Abstract

Streptococcus pneumoniae (pneumococcus) remains one of the most commonly identified causes of bacterial infection in the general population, and the risk is 30-100 fold higher in HIV-infected individuals. Both innate and adaptive host immune responses to pneumococcal infection are important against pathogen invasion. Pneumococcal-specific IgA antibody (Ab) is key to control infection at the mucosal sites. Ab responses against pneumococcal infection by B cells can be generated through T cell-dependent or T cell-independent pathways. Depletion of CD4+ T cells is a hallmark of immunodeficiency in HIV infection and this defect also contributes to B cell dysfunction, which predisposes to infections such as the pneumococcus. Two pneumococcal vaccines have been demonstrated to have potential benefits for HIV-infected patients. One is a T cell dependent 13-valent pneumococcal conjugate vaccine (PCV13); the other is a T cell independent 23-valent pneumococcal polysaccharide vaccine (PPV23). However, many questions remain unknown regarding these two vaccines in the clinical setting in HIV disease. Here we review the latest research regarding B cell immune responses against pneumococcal antigens, whether derived from potentially invading pathogens or vaccinations, in the setting of HIV-1 infection.

Copyright © 2015 Elsevier Ltd. All rights reserved.

KEYWORDS:

B cells; HIV; Humoral immune responses; Streptococcus pneumoniae

PMID: 26141012 [PubMed - as supplied by publisher]

Auranofin efficacy against MDR Streptococcus pneumoniae and Staphylococcus aureus infections.

J Antimicrob Chemother. 2015 Jul 4. pii: dkv163. [Epub ahead of print]

Auranofin efficacy against MDR Streptococcus pneumoniae and Staphylococcus aureus infections.

Aguinagalde L1, Díez-Martínez R2, Yuste J3, Royo I4, Gil C5, Lasa Í5, Martín-Fontecha M6, Marín-Ramos NI7, Ardanuy C8, Liñares J8, García P2, García E2, Sánchez-Puelles JM9.

Author information

Abstract

BACKGROUND:

Auranofin is an FDA-approved, gold-containing compound in clinical use for the oral treatment of rheumatoid arthritis and has been recently granted by the regulatory authorities due to its antiprotozoal properties.

METHODS:

A reprofiling strategy was performed with a Streptococcus pneumoniae phenotypic screen and a proprietary library of compounds, consisting of both FDA-approved and unapproved bioactive compounds. Two different multiresistant S. pneumoniae strains were employed in a sepsis mouse model of infection. In addition, an MRSA strain was tested using both the thigh model and a mesh-associated biofilm infection in mice.

RESULTS:

The repurposing approach showed the high potency of auranofin against multiresistant clinical isolates of S. pneumoniae and Staphylococcus aureus in vitro and in vivo. Efficacy in the S. pneumoniae sepsis model was obtained using auranofin by the oral route in the dose ranges used for the treatment of rheumatoid arthritis. Thioglucose replacement by alkyl chains showed that this moiety was not essential for the antibacterial activity and led to the discovery of a new gold derivative (MH05) with remarkable activity in vitro and in vivo.

CONCLUSIONS:

Auranofin and the new gold derivative MH05 showed encouraging in vivo activity against multiresistant clinical isolates of S. pneumoniae and S. aureus. The clinical management of auranofin, alone or in combination with other antibiotics, deserves further exploration before use in patients presenting therapeutic failure caused by infections with multiresistant Gram-positive pathogens. Decades of clinical use mean that this compound is safe to use and may accelerate its evaluation in humans.

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PMID: 26142477 [PubMed - as supplied by publisher]

Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae.

Lab Anim Res. 2015 Jun;31(2):78-85. doi: 10.5625/lar.2015.31.2.78. Epub 2015 Jun 26.

Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae.

Jeong DG1, Seo JH2, Heo SH3, Choi YK1, Jeong ES4.

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Abstract

Streptococcus pneumoniae is a major human pathogen that is involved in community-acquired pneumonia. Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that activates immune responses against infection, invasion, injury, or inflammation. To study the role of TNF-α during S. pneumoniae infection, a murine pneumococcal pneumonia model was used. We intranasally infected C57BL/6J wild-type (WT) and TNF-α knockout (KO) mice with S. pneumoniae D39 serotype 2. In TNF-α KO mice, continuous and distinct loss of body weight, and low survival rates were observed. Bacterial counts in the lungs and blood of TNF-α KO mice were significantly higher than those in WT mice. Histopathological lesions in the spleen of TNF-α KO mice were more severe than those in WT mice. In TNF-α KO mice, severe depletion of white pulp was observed and the number of apoptotic cells was significantly increased. Interferon-gamma (IFN-γ), IL-12p70 and IL-10 levels in serum were significantly increased in TNF-α KO mice. TNF-α is clearly involved in the regulation of S. pneumoniae infections. Early death and low survival rates of TNF-α KO mice were likely caused by a combination of impaired bacterial clearance and damage to the spleen. Our findings suggest that TNF-α plays a critical role in protecting the host from systemic S. pneumoniae infection.

KEYWORDS:

Streptococcus pneumoniae; Tumor necrosis factor-alpha knockout; pneumonia

PMID: 26155202 [PubMed] PMCID: PMC4490149 

Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae.

J Mol Microbiol Biotechnol. 2015;25(2-3):120-8. doi: 10.1159/000377724. Epub 2015 Jul 9.

Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae.

Manzoor I1, Shafeeq S, Afzal M, Kuipers OP.

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Abstract

In this study, we explore the impact of fucose on the transcriptome of S. pneumoniae D39. The expression of various genes and operons, including the fucose uptake PTS and utilization operon (fcs operon) was altered in the presence of fucose. By means of quantitative RT-PCR and β-galactosidase analysis, we demonstrate the role of the transcriptional regulator FcsR, present upstream of the fcs operon, as a transcriptional activator of the fcs operon. We also predict a 19-bp putative FcsR regulatory site (5'-ATTTGAACATTATTCAAGT-3') in the promoter region of the fcs operon. The functionality of this predicted FcsR regulatory site was further confirmed by promoter-truncation experiments, where deletion of half of the FscR regulatory site or full deletion led to the abolition of expression of the fcs operon. © 2015 S. Karger AG, Basel.

PMID: 26159073 [PubMed - in process]

Dynamics of serotype 14 Streptococcus pneumoniae population causing acute respiratory infections among children in China (1997-2012).

BMC Infect Dis. 2015 Jul 11;15:266. doi: 10.1186/s12879-015-1008-7.

Dynamics of serotype 14 Streptococcus pneumoniae population causing acute respiratory infections among children in China (1997-2012).

He M1, Yao K2, Shi W3, Gao W4, Yuan L5, Yu S6, Yang Y3.

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Abstract

BACKGROUND:

In the last decade, the Streptococcus pneumoniae population has changed, mainly due to the abuse of antibiotics. The aim of this study was to determine the genetic structure of 144 S. pneumonia serotype 14 isolates collected from children with acute respiratory infections during 1997-2012 in China.

METHODS:

All isolated pneumococci were tested for their sensitivity to 11 kinds of antibiotics with the E-test method or disc diffusion. The macrolides resistance genes ermB and mefA, as well as the sulfamethoxazole-trimethoprim resistance gene dihydrofolate reductase (DHFR) were detected by polymerase chain reaction (PCR). The sequence types (STs) were analyzed with multilocus sequence typing (MLST).

RESULTS:

From 1997 to 2012, the percentage of serotype 14 S. pneumonia isolates in the whole isolates increased. All of the 144 serotype 14 S. pneumonia isolates were susceptible to amoxicillin-clavulanic acid, vancomycin and levofloxacin. No penicillin resistant isolate was found, and the intermediate rate was as low as 0.7 %. Erythromycin resistance was confirmed among 143 isolates. The ermB gene was determined in all erythromycin resistant isolates, and the mefA gene was positive additionally in 13 of them. The non-susceptibility rate to the tested cephalosporins increased from 1997-2012. All trimethoprim-resistant isolates contained the Ile100-Leu mutation. Overall, 30 STs were identified, among which ST876 was the most prevalent, followed by ST875. During the study period, the percentage of CC876 increased from 0 % in 1997-2000 to 96.4 % in 2010-2012, whereas CC875 decreased from 84.2 to 0 %. CC876 showed higher non-susceptibility rates to β-lactam antibiotics than CC875.

CONCLUSION:

The percentage of serotype 14 S. pneumonia isolates increased over time in China. The increase of resistance to β-lactam antibiotics in this serotype isolates was associated with the spread of CC876.

PMID: 26163293 [PubMed - in process] PMCID: PMC4499228 

Multidrug-Resistant Streptococcus pneumoniae Isolates from Healthy Ghanaian Preschool Children.

Microb Drug Resist. 2015 Jul 14. [Epub ahead of print]

Multidrug-Resistant Streptococcus pneumoniae Isolates from Healthy Ghanaian Preschool Children.

Dayie NT1,2, Arhin RE1, Newman MJ1, Dalsgaard A2, Bisgaard M2, Frimodt-Møller N3, Slotved HC4.

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Abstract

Streptococcus pneumoniae is the cause of high mortality among children worldwide. Antimicrobial treatment and vaccination are used to control pneumococcal infections. In Ghana, data on antimicrobial resistance and the prevalence of multidrug-resistant pneumococcal clones are scarce; hence, the aim of this study was to determine the antibiogram of S. pneumoniae recovered from Ghanaian children younger than six years of age and to what extent resistances were due to the spread of certain sero- and multilocus sequence typing (MLST) types. The susceptibility of 115 pneumococcal isolates, recovered in a previous study, to six antimicrobials was determined by disk diffusion test. Overall, 90.4% of isolates were intermediate penicillin resistant, 99.1% were trimethoprim resistant, 73.0% were tetracycline resistant, and 33.9% were sulfamethoxazole resistant. Low resistance was recorded for erythromycin (2.6%) and cefotaxime (5.2%). Overall, 72.2% of isolates were resistant to penicillin (I or R) and at least two other antimicrobials. MLST of 20 isolates showing resistance to at least four antimicrobials revealed a high diversity documented by 16 different clones, none of which had previously been associated with multidrug resistance. The resistances found may have emerged due to nonprudent antimicrobial use practices and there is a need to monitor and promote prudent antimicrobial usage in Ghana.

PMID: 26172078 [PubMed - as supplied by publisher]

Absence of Capsule Reveals Glycan-Mediated Binding and Recognition of Salivary Mucin MUC7 by Streptococcus pneumoniae.

Mol Oral Microbiol. 2015 Jul 14. doi: 10.1111/omi.12113. [Epub ahead of print]

Absence of Capsule Reveals Glycan-Mediated Binding and Recognition of Salivary Mucin MUC7 by Streptococcus pneumoniae.

Thamadilok S1, Roche-Håkansson H2, Håkansson AP2, Ruhl S1.

Author information

Abstract

Salivary proteins modulate bacterial colonization in the oral cavity and interact with systemic pathogens that pass through the oropharynx. An interesting example is the opportunistic respiratory pathogen Streptococcus pneumoniae that normally resides in the nasopharynx, but belongs to the greater Mitis group of streptococci, most of which colonize the oral cavity. S. pneumoniae also expresses a serine-rich repeat (SRR) adhesin, PsrP, that is a homologue to oral Mitis group SRR adhesins, such as Hsa of S. gordonii and SrpA of S. sanguinis. Since the latter bind to salivary glycoproteins through recognition of terminal sialic acids, we wanted to determine whether S. pneumoniae also binds to salivary proteins through possibly the same mechanism. We found that only a capsule-free mutant of S. pneumoniae TIGR4 binds to salivary proteins, most prominently to mucin MUC7, but that this binding was not mediated through PsrP or recognition of sialic acid. We also found, however, that PsrP is involved in agglutination of human red blood cells (RBCs). After removal of PsrP, an additional previously masked lectin-like adhesin activity mediating agglutination of sialidase-treated RBCs becomes revealed. Using a custom-spotted glycoprotein and neoglycoprotein dot blot array, we identify candidate glycan motifs recognized by PsrP and by the putative S. pneumoniae adhesin that could perhaps be responsible for pneumococcal binding to salivary MUC7 and glycoproteins on RBCs. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:

Saliva; bacterial lectins; salivary proteins; serine-rich repeat adhesins

PMID: 26172471 [PubMed - as supplied by publisher]

Serotyping, Antibiotic Susceptibility and Related Risk Factors Aspects of Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy School Students.

Iran J Public Health. 2014 Sep;43(9):1284-90.

Serotyping, Antibiotic Susceptibility and Related Risk Factors Aspects of Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy School Students.

Mirzaei Ghazikalayeh H1, Moniri R2, Moosavi SG3, Rezaei M1, Yasini M1, Valipour M1.

Author information

Abstract

BACKGROUND:

Streptococcus pneumoniae is an important problem worldwide and nasopharyngeal colonization plays significant role in pneumococcal infections. The aims of this study were to determine the nasopharyngeal colonization rate, serotyping, antibiotics susceptibility and study the risk factors for nasopharyngeal colonization with S. pneumoniae in students in Kashan, Iran.

METHODS:

A cross-sectional study was conducted on children aged 7 to 19 years from December 2011 to November 2012. Nasopharyngeal swabs were plated onto brain heart infusion agar plates with 5% sheep blood and 4µg/ml of gentamycin. Antimicrobial susceptibility profiles were determined on Mueller-Hinton agar in accordance with CLSI. S. pneumoniae strains were investigated for the presence of the most common pneumococcal serotypes using a multiplex polymerase chain reaction.

RESULTS:

13.9% were found to be carriers. The most prevalent serogroups were 19F (30%), 6A/B (18.9%), 15A (16.5%), 11 (11.3%), 23F (8.2%), 1 (6.2%), 19A (3.4%), and 35B (2.4%). Nine strains (3.1%) were non-typeable. The carrier rate was significantly higher in 12 to15 year old age group. Upper respiratory tract infections within the last month (OR=1.5, P<0.011), previous hospitalization (OR=1.6, P<0.001), previous antibiotic usage last two weeks (OR=1.89, P<0.001), rhinorea (OR=1.9 P<0.001), male sex (OR=3.5 P< 0.001) and passive smoking (OR=1.56, P< 0.001) have been determined to be risk factors for S. pneumoniae carriage. The highest pneumococcal resistance was to tetracycline (25.4%). All strains were susceptible to linezolid and levofloxacin.

CONCLUSION:

Our information leads to an important source to screen the future impact of pneumococcal vaccination on bacterial colonization.

KEYWORDS:

Antibiotic resistance; Nasopharygeal; Serogroup; Streptococcus pneumoniae

PMID: 26175983 [PubMed] PMCID: PMC4500431 

Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae.

PLoS Pathog. 2015 Jul 16;11(7):e1005034. doi: 10.1371/journal.ppat.1005034. eCollection 2015.

Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae.

Watkins ER1, Penman BS1, Lourenço J1, Buckee CO2, Maiden MC1, Gupta S1.

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Abstract

The bacterial pathogen, Streptococcus pneumoniae (the pneumococcus), is a leading cause of life-threatening illness and death worldwide. Available conjugate vaccines target only a small subset (up to 13) of >90 known capsular serotypes of S. pneumoniae and, since their introduction, increases in non-vaccine serotypes have been recorded in several countries: a phenomenon termed Vaccine Induced Serotype Replacement (VISR). Here, using a combination of mathematical modelling and whole genome analysis, we show that targeting particular serotypes through vaccination can also cause their metabolic and virulence-associated components to transfer through recombination to non-vaccine serotypes: a phenomenon we term Vaccine-Induced Metabolic Shift (VIMS). Our results provide a novel explanation for changes observed in the population structure of the pneumococcus following vaccination, and have important implications for strain-targeted vaccination in a range of infectious disease systems.

PMID: 26181911 [PubMed - in process] PMCID: PMC4504489

Induced tigecycline resistance in Streptococcus pneumoniae mutants reveals mutations in ribosomal proteins and rRNA.

J Antimicrob Chemother. 2015 Jul 16. pii: dkv211. [Epub ahead of print]

Induced tigecycline resistance in Streptococcus pneumoniae mutants reveals mutations in ribosomal proteins and rRNA.

Lupien A1, Gingras H1, Leprohon P1, Ouellette M2.

Author information

Abstract

OBJECTIVES:

Tigecycline is a broad-spectrum antibiotic acting at the level of the 30S ribosomal subunit to inhibit translation. While Streptococcus pneumoniae remains susceptible to tigecycline, resistance is beginning to emerge in some species and mainly involves efflux or mutations in ribosome constituents. We describe here the characterization of S. pneumoniae mutants selected for resistance to tigecycline.

METHODS:

Molecular determinants of resistance to tigecycline in S. pneumoniae were studied through WGS of two series of mutants made resistant to tigecycline in vitro in a stepwise fashion and by reconstructing tigecycline resistance using DNA transformation.

RESULTS:

The tigecycline-resistant S. pneumoniae M1TGC-6 and M2TGC-6 mutants were cross-resistant to tetracycline and minocycline. A role in tigecycline resistance could be attributed to 4 of the 12 genes that were mutated in both mutants. Mutations in ribosomal proteins S10 and S3, acquired early and late during selection, respectively, were implicated in resistance in both mutants. Similarly, mutations were detected in the four alleles of the 16S ribosomal RNA at sites involved in tigecycline binding and the number of mutated alleles correlated with the level of resistance. Finally, the gene spr1784 encodes an RsmD-like 16S rRNA methyltransferase for which inactivating mutations selected in the S. pneumoniae tigecycline-resistant mutants were found to decrease susceptibility to tigecycline.

CONCLUSIONS:

This first report about tigecycline resistance mechanisms in S. pneumoniae revealed that, in contrast to Gram-negative species, for which efflux appears central for tigecycline resistance, resistance in the pneumococcus occurs through mutations related to ribosomes.

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PMID: 26183184 [PubMed - as supplied by publisher]

Identification of PblB mediating galactose-specific adhesion in a successful Streptococcus pneumoniae clone.

Sci Rep. 2015 Jul 21;5:12265. doi: 10.1038/srep12265.

Identification of PblB mediating galactose-specific adhesion in a successful Streptococcus pneumoniae clone.

Hsieh YC1, Lin TL2, Lin CM1, Wang JT3.

Author information

Abstract

The pneumococcal genome is variable and there are minimal data on the influence of the accessory genome on phenotype. Pneumococcal serotype 14 sequence type (ST) 46 had been the most prevalent clone causing pneumonia in children in Taiwan. A microarray was constructed using the genomic DNA of a clinical strain (NTUH-P15) of serotype 14 ST46. Using DNA hybridization, genomic variations in NTUH-P15 were compared to those of 3 control strains. Microarray analysis identified 7 genomic regions that had significant increases in hybridization signals in the NTUH-P15 strain compared to control strains. One of these regions encoded PblB, a phage-encoded virulence factor implicated (in Streptococcus mitis) in infective endocarditis. The isogenic pblB mutant decreased adherence to A549 human lung epithelial cell compared to wild-type NTUH-P15 strain (P = 0.01). Complementation with pblB restored the adherence. PblB is predicted to contain a galactose-binding domain-like region. Preincubation of NTUH-P15 with D-galactose resulted in decreases of adherence to A549 cell in a dose-dependent manner. Challenge of mice with NTUH-P15, isogenic pblB mutant and pblB complementation strains determined that PblB was required for bacterial persistence in the nasopharynx and lung. PblB, as an adhesin mediating the galactose-specific adhesion activity of pneumococci, promote pneumococcal clonal success.

PMID: 26193794 [PubMed - in process] PMCID: PMC4508584 

A structural snapshot of type II pilus formation in Streptococcus pneumoniae.

J Biol Chem. 2015 Jul 21. pii: jbc.M115.647834. [Epub ahead of print]

A structural snapshot of type II pilus formation in Streptococcus pneumoniae.

Shaik MM1, Lombardi C1, Maragno Trindade D2, Fenel D1, Schoehn G1, Di Guilmi AM1, Dessen A3.

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Abstract

Pili are fibrous appendages expressed on the surface of a vast number of bacterial species, and their role in surface adhesion is important for processes such as infection, colonization, and biofilm formation. The human pathogen Streptococcus pneumoniae expresses two different types of pili, PI-1 and PI-2, both of which require the concerted action of structural proteins and sortases for their polymerization. The type PI-1 streptococcal pilus is a complex, well-studied structure, but the PI-2 type, present in a number of invasive pneumococcal serotypes, has to date remained less well understood. The PI-2 pilus consists of repeated units of a single protein, PitB, whose covalent association is catalyzed by cognate sortase SrtG-1 and partner protein SipA. Here we report the high-resolution crystal structures of PitB and SrtG1 and use molecular modeling to visualize a 'trapped' 1:1 complex between the two molecules. X-ray crystallography and electron microscopy reveal that the pneumococcal PI-2 backbone fiber is formed by PitB monomers associated in 'head-to-tail' fashion, and that short, flexible fibers can be formed even in the absence of coadjuvant proteins. These observations, obtained with a simple pilus biosynthetic system, are likely to be applicable to other fiber formation processes in a variety of Gram-positive organisms.

Copyright © 2015, The American Society for Biochemistry and Molecular Biology.

KEYWORDS:

X-ray crystallography; bacterial pathogenesis; microbiology; sortase A; virulence factor

PMID: 26198632 [PubMed - as supplied by publisher]

Chemical Synthesis Elucidates the Immunological Importance of a Pyruvate Modification in the Capsular Polysaccharide of Streptococcus pneumoniae Serotype 4.

Angew Chem Int Ed Engl. 2015 Jul 24. doi: 10.1002/anie.201504847. [Epub ahead of print]

Chemical Synthesis Elucidates the Immunological Importance of a Pyruvate Modification in the Capsular Polysaccharide of Streptococcus pneumoniae Serotype 4.

Pereira CL1,2, Geissner A3,4, Anish C3,4, Seeberger PH5,6.

Author information

Abstract

Carbohydrate modifications are believed to strongly affect the immunogenicity of glycans. Capsular polysaccharides (CPS) from bacterial pathogens are frequently equipped with a pyruvate that can be placed across the 4,6-, 3,4-, or 2,3-positions. A trans-2,3-linked pyruvate is present on the CPS of the Gram-positive bacterium Streptococcus pneumoniae serotype 4 (ST4), a pathogen responsible for pneumococcal infections. To assess the immunological importance of this modification within the CPS repeating unit, the first total synthesis of the glycan was carried out. Glycan microarrays containing a series of synthetic antigens demonstrated how antibodies raised against natural ST4 CPS specifically recognize the pyruvate within the context of the tetrasaccharide repeating unit. The pyruvate modification is a key motif for designing minimal synthetic carbohydrate vaccines for ST4.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

Streptococcus pneumoniae; antigens; oligosaccharides; pyruvate acetal; synthetic vaccines

PMID: 26212109 [PubMed - as supplied by publisher]

Antibiotic resistance of Streptococcus pneumoniae colonizing the nasopharynx of HIV-exposed Tanzanian infants.

Trop Med Int Health. 2015 Jul 30. doi: 10.1111/tmi.12582. [Epub ahead of print]

Antibiotic resistance of Streptococcus pneumoniae colonizing the nasopharynx of HIV-exposed Tanzanian infants.

Bles P1, de Mast Q2,3, van der Gaast-de Jongh CE1,2, Kinabo GD4, Kibiki G5, van de Ven A2,3, de Jonge MI1,2.

Author information

Abstract

OBJECTIVES:

To determine antibiotic susceptibility of colonizing pneumococcal serotypes in HIV-exposed infants before the introduction of the 13-valent Pneumococcal Conjugate Vaccine (PCV13), because HIV-exposed infants are at increased risk for invasive pneumococcal infections.

METHODS:

Antibiotic susceptibility of 104 pneumococcal isolates, cultured from the nasopharynx from Tanzanian HIV-exposed infants, was determined using the disk diffusion method and the E-test according to EUCAST version 4.0 (2014) criteria.

RESULTS:

69.2% of isolates were intermediately susceptible for benzyl penicillin (MIC 0.06 - 2 mg L-1); no high level resistance was found. All isolates but one were susceptible to ampicillin. Regarding non-beta-lactam antibiotics, 19.2% of isolates were resistant to doxycycline, 3.8% to erythromycin and 97.1% to trimethoprim/sulfamethoxazole. 15.4% of isolates were resistant to three antibiotic classes or more. There were no differences in antibiotic susceptibility between vaccine and non-vaccine serotypes. Reduced susceptibility of colonizing pneumococcal isolates for commonly used antibiotics is common in HIV-exposed Tanzanian infants.

CONCLUSIONS:

High dose penicillin and ampicillin remain appropriate first choices for non-meningeal pneumococcal infections in this group. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:

Streptococcus pneumoniae ; Colonization; HIV-exposed infants; Tanzania; antibiotic resistance

PMID: 26224321 [PubMed - as supplied by publisher]

Virulence Factors of Streptococcus pneumoniae. Comparison between African and French Invasive Isolates and Implication for Future Vaccines.

PLoS One. 2015 Jul 27;10(7):e0133885. doi: 10.1371/journal.pone.0133885. eCollection 2015.

Virulence Factors of Streptococcus pneumoniae. Comparison between African and French Invasive Isolates and Implication for Future Vaccines.

Blumental S1, Granger-Farbos A2, Moïsi JC3, Soullié B2, Leroy P2, Njanpop-Lafourcade BM3, Yaro S4, Nacro B5, Hallin M6, Koeck JL2.

Author information

Abstract

BACKGROUND: 

Many surface proteins thought to promote Streptocococcus pneumoniae virulence have recently been discovered and are currently being considered as future vaccine targets. We assessed the prevalence of 16 virulence genes among 435 S. pneumoniae invasive isolates from France and the "African meningitis belt" region, with particular focus on serotype 1 (Sp1), to compare their geographical distribution, assess their association with site of infection and evaluate their potential interest as new vaccine candidates.

METHODS: 

Detection by PCR of pspA (+families), pspC (+pspC.4), pavA, lytA, phtA,B,D,E, nanA,B,C, rrgA (Pilus-1), sipA (Pilus-2), pcpA and psrp was performed on all isolates, as well as antibiotic resistance testing and MLVA typing (+MLST on 54 representative strains). Determination of ply alleles was performed by sequencing (Sp1 isolates).

RESULTS: 

MLVA and virulence genes profiles segregated Sp1 isolates into 2 groups that followed continent distribution. The ply allele 5 and most of the genes that were variable (nanC, Pilus-2, psrp, pcpA, phtD) were present in the French Sp1 isolates (PMEN clone Sweden1-28, ST306) but absent from the African ones. Whereas all African Sp1 isolates clustered into a single MLST CC (CC217), MLVA distinguished two CCs that followed temporal evolution. Pilus-2 and psrp were more prevalent in bacteraemic pneumonia yielded isolates and phtB in meningitis-related isolates. Considering vaccine candidates, phtD was less prevalent than anticipated (50%) and pcpA varied importantly between France and Africa (98% versus 34%). Pilus-1 was carried by 7-11% of isolates and associated with β-lactams resistance.

CONCLUSIONS: 

Most virulence genes were carried by the European ST306 clone but were lacking on Sp1 isolates circulating in the African meningitis belt, where a more serious pattern of infection is observed. While virulence proteins are now considered as vaccine targets, the geographical differences in their prevalence could affect the efficacy expected from future vaccines.

PMID: 26214695 [PubMed - in process] PMCID: PMC4516325 

Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae - Alaska, 2000-2010

Pediatr Infect Dis J. 2015 Jul 29. [Epub ahead of print]

Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae - Alaska, 2000-2010.

Gounder PP1, Brewster M, Bruce MG, Bruden DJ, Rudolph K, Hurlburt DA, Hennessy TW.

Author information

Abstract

BACKGROUND:

We describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic resistant pneumococci in urban Alaskan children during 2000-2010.

METHODS:

We obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use <90days before enrollment was determined by interview/medical records review.Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS.

RESULTS:

We recruited 3,496 children (median: 452/year). During 2000-2010, a range of 18-29%/year of children used PCN/amoxicillin (p-value for trend [p] = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0%-90%; p <0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53%-<1%; p <0.01) and non-PCV7-serotype proportion increased (43%-95%; p <0.01). PCN-R pneumococcal colonizationprevalence decreased (23%-9%, p <0.01) and PCN-I pneumococcal colonization prevalence increased (13%-24%, p <0.01); overall PCN-NS pneumococcalcolonizationprevalence was unchanged. PCN-NS among colonizing PCV7-type and non-PCV7-type pneumococci remained unchanged; a mean of 31%/year of PCV7-type and 10%/year of non-PCV7-type isolates were PCN-R, and 10%/year of PCV7 and 20%/year of non-PCV7-type isolates were PCN-I.

CONCLUSIONS:

Overall PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype-groups (PCV7 versus non-PCV7) despite stable penicillin use in our population.

PMID: 26226443 [PubMed - as supplied by publisher]

In vitro susceptibility of a penicillin-resistant and tolerable isolate of Streptococcus pneumoniae to combination therapy.

J Infect Dev Ctries. 2015 Jul 30;9(7):702-9. doi: 10.3855/jidc.4711.

In vitro susceptibility of a penicillin-resistant and tolerable isolate of Streptococcus pneumoniae to combination therapy.

Majhi A1, Nandi A, Adhikary R, Mahanti S, Bishayi B.

Author information

Abstract

INTRODUCTION:

Preference for combination therapy to treat infection due to multidrug-resistant S. pneumoniae (MDRSP) has not been well elucidated in previous studies.

METHODOLOGY:

In the present study, 19 antibiotics in combinations were tested against an MDRSP isolate. In vitro susceptibility studies including minimum inhibitory concentration (MIC), minimal bactericidal concentrations (MBC) and disk agar diffusion (DAD), tolerance to resistant antibiotics, checkerboard assay, time-kill curve, hemolytic assay, and autolysis assay were performed on the test strain to study its in vitro susceptibility to combination therapy.

RESULTS:

From the checkerboard assay and time-kill curve, it was observed that a combination of levofloxacin (MIC, 16 µg/mL) and ceftriaxone (MIC, 2 µg/mL), at sub-MIC concentration was synergistic and most effective against the MDRSP isolate (penicillin MIC, > 64 µg/mL). Hemolytic activities also increased significantly with combination therapy compared to monotherapy (p < 0.05). Moreover, the hemolytic activity of levofloxacin in combination with ceftriaxone was better than ciprofloxacin plus ceftriaxone or cefepime. The autolysis rate was also found to increase rapidly within one hour of exposure to levofloxacin plus ceftriaxone, and this was found to be significantly different from the other combinations at the fifth and sixth hour post incubation (p < 0.05).

CONCLUSIONS:

This data suggests that this combination is bactericidal in vitro, and requires further studies in in vivo models for treatment against MDRSP infections.

PMID: 26230119 [PubMed - in process] 

Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG).

Clin Exp Immunol. 2015 Jun 9. doi: 10.1111/cei.12665. [Epub ahead of print]

Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG).

Knutsen AP1, Leiva LE2, Caruthers C1, Rodrigues J1, Sorensen RU2.

Author information

Abstract

Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titres to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of immunoglobulin (Ig)G/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titres were ≥ 1·3 μg/ml to 99·4 ± 2·1% of the 14 serotypes at peak IVIG but decreased to 66·9 ± 19·8% at trough IVIG. Loss of Spn titres ≥ 1·3 μg/ml was most frequent for Spn serotypes 1, 4, 9V and 23. This correlated with lower Spn antibody titres to these serotypes at peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titres were protective to 58·2 ± 23·3% of the serotypes 3-5 days after infusion, similar to trough IVIG. Similarly, the Spn serotypes with the least protective percentages were the same as the ones observed in trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG-treated group, 0·8 ± 0·7 versus 2·2 ± 1·2 infections/patient/year (P = 0·004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titres.

© 2015 British Society for Immunology.

KEYWORDS:

B cell; antibodies; immunodeficiency diseases

PMID: 26230522 [PubMed - as supplied by publisher]

Antimicrobial Susceptibility/Resistance of Streptococcus Pneumoniae.

Mater Sociomed. 2015 Jun;27(3):180-4. doi: 10.5455/msm.2015.27.180-184. Epub 2015 Jun 8.

Antimicrobial Susceptibility/Resistance of Streptococcus Pneumoniae.

Karcic E1, Aljicevic M2, Bektas S3, Karcic B4.

Author information

Abstract

INTRODUCTION:

Pneumococcal infections are a major cause of morbidity and mortality worldwide, whose treatment is threatened with an increase in the number of strains resistant to antibiotic therapy.

GOAL:

The main goal of this research was to investigate the presence of antimicrobial susceptibility/resistance of S. pneumoniae.

MATERIAL AND METHODS:

Taken are swabs of the nose and nasopharynx, eye and ear. In vitro tests that were made in order to study the antimicrobial resistance of pneumococci are: disk diffusion method and E-test.

RESULTS:

The resistance to inhibitors of cell wall synthesis was recorded at 39.17%, protein synthesis inhibitors 19.67%, folate antagonists 47.78% and quinolone in 1.11%. S. pneumoniae has shown drug resistance to erythromycin in 45%, clindamycin in 45%, chloramphenicol-0.56%, rifampicin-6.11%, tetracycline-4.67%, penicillin-G in 4.44%, oxacillin in 73.89%, ciprofloxacin in 1.11% and trimethoprim-sulfamethoxazole in 5.34% of cases.

CONCLUSION:

The highest resistance pneumococcus showed to erythromycin, clindamycin and trimethoprim-sulfamethoxazole and these should be avoided in the treatment. The least resistance pneumococcus showed to tetracycline, rifampicin, chloramphenicol, penicillin-G and ciprofloxacin.

KEYWORDS:

antibiotics; pneumococcus; resistance; susceptibility

PMID: 26236165 [PubMed]

Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

PLoS One. 2015 May 13;10(5):e0127098. doi: 10.1371/journal.pone.0127098. eCollection 2015.

Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

Nguyen DT1, Louwen R2, Elberse K3, van Amerongen G1, Yüksel S1, Luijendijk A2, Osterhaus AD1, Duprex WP4, de Swart RL1.

Author information

Abstract

Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies.

PMID: 25970287 [PubMed - in process] PMCID: PMC4430531 

Vinpocetine Inhibits Streptococcus pneumoniae-Induced Upregulation of Mucin MUC5AC Expression via Induction of MKP-1 Phosphatase in the Pathogenesis of Otitis Media.

J Immunol. 2015 May 13. pii: 1401489. [Epub ahead of print]

Vinpocetine Inhibits Streptococcus pneumoniae-Induced Upregulation of Mucin MUC5AC Expression via Induction of MKP-1 Phosphatase in the Pathogenesis of Otitis Media.

Lee JY1, Komatsu K1, Lee BC1, Miyata M1, O'Neill Bohn A1, Xu H1, Yan C2, Li JD3.

Author information

Abstract

Mucin overproduction is a hallmark of otitis media (OM). Streptococcus pneumoniae is one of the most common bacterial pathogens causing OM. Mucin MUC5AC plays an important role in mucociliary clearance of bacterial pathogens. However, if uncontrolled, excessive mucus contributes significantly to conductive hearing loss. Currently, there is a lack of effective therapeutic agents that suppress mucus overproduction. In this study, we show that a currently existing antistroke drug, vinpocetine, a derivative of the alkaloid vincamine, inhibited S. pneumoniae-induced mucin MUC5AC upregulation in cultured middle ear epithelial cells and in the middle ear of mice. Moreover, vinpocetine inhibited MUC5AC upregulation by inhibiting the MAPK ERK pathway in an MKP-1-dependent manner. Importantly, ototopical administration of vinpocetine postinfection inhibited MUC5AC expression and middle ear inflammation induced by S. pneumoniae and reduced hearing loss and pneumococcal loads in a well-established mouse model of OM. Thus, these studies identified vinpocetine as a potential therapeutic agent for inhibiting mucus production in the pathogenesis of OM.

Copyright © 2015 by The American Association of Immunologists, Inc.

PMID: 25972475 [PubMed - as supplied by publisher]