scholarly journals Variation in the Presence of Neuraminidase Genes among Streptococcus pneumoniae Isolates with Identical Sequence Types

2006 ◽  
Vol 74 (6) ◽  
pp. 3360-3365 ◽  
Author(s):  
Melinda M. Pettigrew ◽  
Kristopher P. Fennie ◽  
Matthew P. York ◽  
Janeen Daniels ◽  
Faryal Ghaffar
Keyword(s):  
Streptococcus Pneumoniae ◽  
Young Children ◽  
Invasive Disease ◽  
Virulence Determinants ◽  
Upper Respiratory Tract ◽  
Capsule Type ◽  
Virulence Potential ◽  
The Relationship ◽  
Sequence Types ◽  
Specific Virulence

ABSTRACT Streptococcus pneumoniae frequently colonizes the upper respiratory tract of young children and is an important cause of otitis media and invasive disease. Carriage is more common than disease, yet the genetic factors that predispose a given clone for disease are not known. The relationship between capsule type, genetic background, and virulence is complex, and important questions remain regarding how pneumococcal clones differ in their ability to cause disease. Pneumococcal neuraminidase cleaves sialic acid-containing substrates and is thought to be important for pneumococcal virulence. We describe the distribution of multilocus sequence types (ST), capsule type, and neuraminidase genes among 342 carriage, middle ear, blood, and cerebrospinal fluid (CSF) pneumococcal strains from young children. We found 149 STs among our S. pneumoniae isolates. nanA was present in all strains, while nanB and nanC were present in 96% and 51% of isolates, respectively. The distribution of nanC varied among the strain collections from different tissue sources (P = 0.03). The prevalence of nanC was 1.41 (95% confidence interval, 1.11, 1.79) times higher among CSF isolates than among carriage isolates. We identified isolates of the same ST that differed in the presence of nanB and nanC. These studies demonstrate that virulence determinants, other than capsule loci, vary among strains of identical ST. Our studies suggest that the presence of nanC may be important for tissue-specific virulence. Studies that both incorporate MLST and take into account additional virulence determinants will provide a greater understanding of the pneumococcal virulence potential.

scholarly journals Identification of colonisation and virulence determinants of Streptococcus pneumoniae via experimental evolution in mouse infection models

2020 ◽  
Author(s):  
Angharad E Green ◽  
Deborah Howarth ◽  
Chrispin Chaguza ◽  
Haley Echlin ◽  
R Frèdi Langendonk ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Experimental Evolution ◽  
Parallel Evolution ◽  
Serial Passage ◽  
Invasive Disease ◽  
Virulence Determinants ◽  
Upper Respiratory Tract ◽  
Single Nucleotide ◽  
Single Nucleotide Change ◽  
Infection Models

AbstractStreptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. Pneumococcus stimulates upper respiratory tract inflammation that promotes shedding from mucosal surfaces and transmission to new hosts. Colonisation and transmission are partially antagonistic processes. Adhesion to surfaces and evasion of host responses favours the former, whilst detachment, promoted by inflammation, is necessary for the latter. We sought to determine how adaptation and evolution of pneumococcus within its nasopharyngeal niche might progress when selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci in mouse models of nasopharyngeal carriage, manually transferring bacteria between mice. To assess the role of host environmental factors on pneumococcal evolution, we also performed analogous experimental evolution in a mouse pneumonia model, passaging pneumococci through lungs. Nasopharynx-passaged pneumococci became more effective colonisers, whilst those evolved within lungs showed reduced virulence. We observed selection of mutations in genes associated with cell wall biogenesis and metabolism in both nasopharynx and lung lineages, but identified prominent examples of parallel evolution that were niche specific. We focussed on gpsA, a gene in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We identified a single nucleotide change conferring resistance to oxidative stress and enhanced nasopharyngeal colonisation potential. We show that gpsA is also a frequent target of mutation during human colonisation. These findings highlight the role played by the host environment in determining trajectories of bacterial evolution and the potential of experimental evolution in animal infection models for identification of novel pathogen virulence and colonisation factors.

scholarly journals Invasiveness of Serotypes and Clones of Streptococcus pneumoniae among Children in Finland

2005 ◽  
Vol 73 (1) ◽  
pp. 431-435 ◽  
Author(s):  
William P. Hanage ◽  
Tarja H. Kaijalainen ◽  
Ritva K. Syrjänen ◽  
Kari Auranen ◽  
Maija Leinonen ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Confidence Interval ◽  
Multilocus Sequence Typing ◽  
Invasive Disease ◽  
Invasive Infection ◽  
Data Set ◽  
Dramatic Effect ◽  
Life Threatening ◽  
The Difference ◽  
Sequence Types

ABSTRACT Streptococcus pneumoniae (the pneumococcus) causes diseases from otitis media to life-threatening invasive infection. The species is extremely antigenically and clonally diverse. We wished to determine odds ratios (ORs) for serotypes and clones of S. pneumoniae that cause invasive disease in Finland. A total of 224 isolates of S. pneumoniae from cases of invasive disease in children <2 years of age in Finland between 1995 and 1999 were serotyped, and sequence types (STs) were determined by multilocus sequence typing. These STs were compared with a previously published carriage data set. STs from invasive disease were significantly less diverse than those from carriage (invasive disease, 0.038 ± 0.01; carriage, 0.019 ± 0.005). The ORs of serotypes 14, 18C, 19A, and 6B were significantly greater than 1, indicating association with invasive disease. The ORs of 6A and 11A were significantly less than 1. The difference between 6A and 6B is significant, which suggests that relatively subtle changes in the capsule may have a dramatic effect upon disease potential. We found that ST 156, the Spain9V-3 clone which mainly expressed serotype 14 in Finland, is strongly associated with invasive disease (OR, 10.1; 95% confidence interval, 1.3 to 79.5). Significant associations with invasive disease were also detected for STs 482, 191, 124, and 138, and associations with carriage were detected for STs 485 and 62. These results demonstrate the invasive phenotype of the serotype 14 variant of the Spain9V-3 clone and differences between members of the same serogroup in invasive disease potential.

scholarly journals The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold

Open Biology ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 130090 ◽  
Author(s):  
Tim Schulte ◽  
Jonas Löfling ◽  
Cecilia Mikaelsson ◽  
Alexey Kikhney ◽  
Karina Hentrich ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Invasive Disease ◽  
Binding Domain ◽  
Upper Respiratory Tract ◽  
Binding Region ◽  
Sequence Identity ◽  
Novel Variant ◽  
Upper Respiratory ◽  
Β Sheet ◽  
Specific Virulence

Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR 187–385 ) determined to 2.0 Å resolution. BR 187–385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended β-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short β-strands, for interaction with KRT10.

scholarly journals Contributions of Pneumolysin, Pneumococcal Surface Protein A (PspA), and PspC to Pathogenicity of Streptococcus pneumoniae D39 in a Mouse Model

2007 ◽  
Vol 75 (4) ◽  
pp. 1843-1851 ◽  
Author(s):  
Abiodun D. Ogunniyi ◽  
Kim S. LeMessurier ◽  
Rikki M. A. Graham ◽  
James M. Watt ◽  
David E. Briles ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Systemic Disease ◽  
Protein A ◽  
Virulence Gene ◽  
Surface Protein ◽  
Invasive Disease ◽  
Upper Respiratory Tract ◽  
Virulence Proteins ◽  
Pneumococcal Surface Protein A ◽  
Genes Encoding

ABSTRACTSuccessful colonization of the upper respiratory tract byStreptococcus pneumoniaeis an essential first step in the pathogenesis of pneumococcal disease. However, the bacterial and host factors that provoke the progression from asymptomatic colonization to invasive disease are yet to be fully defined. In this study, we investigated the effects of single and combined mutations in genes encoding pneumolysin (Ply), pneumococcal surface protein A (PspA), and pneumococcal surface protein C (PspC, also known as choline-binding protein A) on the pathogenicity ofStreptococcus pneumoniaeserotype 2 (D39) in mice. Following intranasal challenge with D39, stable colonization of the nasopharynx was maintained over a 7-day period at a level of approximately 105bacteria per mouse. The abilities of the mutant deficient in PspA to colonize the nasopharynx and to cause lung infection and bacteremia were significantly reduced. Likewise, the PspC mutant and, to a lesser extent, the Ply mutant also had reduced abilities to colonize the nasopharynx. As expected, the double mutants colonized less well than the parent to various degrees and had difficulty translocating to the lungs and blood. A significant additive attenuation was observed for the double and triple mutants in pneumonia and systemic disease models. Surprisingly, the colonization profile of the derivative lacking all three proteins was similar to that of the wild type, indicating virulence gene compensation. These findings further demonstrate that the mechanism of pneumococcal pathogenesis is highly complex and multifactorial but ascribes a role for each of these virulence proteins, alone or in combination, in the process.

scholarly journals Clonal Spread of mef-Positive Macrolide-Resistant Streptococcus pneumoniae Isolates Causing Invasive Disease in Adults in Germany

2007 ◽  
Vol 51 (5) ◽  
pp. 1830-1834 ◽  
Author(s):  
Mark van der Linden ◽  
Adnan Al-Lahham ◽  
Stefan Haupts ◽  
Ralf René Reinert
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Invasive Disease ◽  
Sequence Type ◽  
Macrolide Resistance ◽  
Erythromycin A ◽  
Clonal Spread ◽  
Sequence Types

ABSTRACT Isolates (3,845) obtained from German adults with invasive pneumococcal disease between 1992 and 2004 were investigated. Of these, 430 isolates (11.2%) were erythromycin A nonsusceptible. Macrolide resistance genotypes and multilocus sequence types were determined. Among the isolates, 35.6% were erm(B) positive and 63.5% were mef positive. Over the study period, the frequency of resistance rose significantly from 2.2 to 17.0% (P < 0.001). A serotype 14, sequence type 9 clone was the most widespread.

scholarly journals Capsule Type and Amount Affect Shedding and Transmission of Streptococcus pneumoniae

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
M. Ammar Zafar ◽  
Shigeto Hamaguchi ◽  
Tonia Zangari ◽  
Michael Cammer ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Human Population ◽  
Capsular Polysaccharide ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Infant Mouse ◽  
Capsule Type ◽  
Upper Respiratory ◽  
Epidemiology Studies

ABSTRACT The capsular polysaccharide (CPS) of Streptococcus pneumoniae is characterized by its diversity, as it has over 95 known serotypes, and the variation in its thickness as it surrounds an organism. While within-host effects of CPS have been studied in detail, there is no information about its contribution to host-to-host transmission. In this study, we used an infant mouse model of intralitter transmission, together with isogenic capsule switch and cps promoter switch constructs, to explore the effects of CPS type and amount. The determining factor in the transmission rate in this model is the number of pneumococci shed in nasal secretions by colonized hosts. Two of seven capsule switch constructs showed reduced shedding. These constructs were unimpaired in colonization and expressed capsules similar in size to those of the wild-type strain. A cps promoter switch mutant expressing ~50% of wild-type amounts of CPS also displayed reduced shedding without a defect in colonization. Since shedding from the mucosal surface may require escape from mucus entrapment, a mucin-binding assay was used to compare capsule switch and cps promoter switch mutants. The CPS type or amount constructs that shed poorly were bound more robustly by immobilized mucin. These capsule switch and cps promoter switch constructs with increased mucin-binding affinity and reduced shedding also had lower rates of pup-to-pup transmission. Our results demonstrate that CPS type and amount affect transmission dynamics and may contribute to the marked differences in prevalence among pneumococcal types. IMPORTANCE Streptococcus pneumoniae, a leading cause of morbidity and mortality, is readily transmitted, especially among young children. Its structurally and antigenically diverse capsular polysaccharide is the target of currently licensed pneumococcal vaccines. Epidemiology studies show that only a subset of the >95 distinct serotypes are prevalent in the human population, suggesting that certain capsular polysaccharide types might be more likely to be transmitted within the community. Herein, we used an infant mouse model to show that both capsule type and amount are important determinants in the spread of pneumococci from host to host. Transmission rates correlate with those capsule types that are better at escaping mucus entrapment, a key step in exiting the host upper respiratory tract. Hence, our study provides a better mechanistic understanding of why certain pneumococcal serotypes are more common in the human population. IMPORTANCE Streptococcus pneumoniae, a leading cause of morbidity and mortality, is readily transmitted, especially among young children. Its structurally and antigenically diverse capsular polysaccharide is the target of currently licensed pneumococcal vaccines. Epidemiology studies show that only a subset of the >95 distinct serotypes are prevalent in the human population, suggesting that certain capsular polysaccharide types might be more likely to be transmitted within the community. Herein, we used an infant mouse model to show that both capsule type and amount are important determinants in the spread of pneumococci from host to host. Transmission rates correlate with those capsule types that are better at escaping mucus entrapment, a key step in exiting the host upper respiratory tract. Hence, our study provides a better mechanistic understanding of why certain pneumococcal serotypes are more common in the human population.

scholarly journals Virulent Combinations of Adhesin and Toxin Genes in Natural Populations of Staphylococcus aureus

2002 ◽  
Vol 70 (9) ◽  
pp. 4987-4996 ◽  
Author(s):  
Sharon J. Peacock ◽  
Catrin E. Moore ◽  
Anita Justice ◽  
Maria Kantzanou ◽  
Lisa Story ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Blood Donors ◽  
Polymorphic Locus ◽  
Natural Populations ◽  
Disease Process ◽  
Invasive Disease ◽  
Virulence Determinants ◽  
Number Of Factors ◽  
Major Predictor ◽  
The Relationship

ABSTRACT Most cases of severe Staphylococcus aureus disease cannot be explained by the action of a single virulence determinant, and it is likely that a number of factors act in combination during the infective process. This study examined the relationship between disease in humans and a large number of putative virulence determinants, both individually and in combination. S. aureus isolates (n = 334) from healthy blood donors and from patients with invasive disease were compared for variation in the presence of 33 putative virulence determinants. After adjusting for the effect of clonality, seven determinants (fnbA, cna, sdrE, sej, eta, hlg, and ica) were significantly more common in invasive isolates. All seven factors contributed independently to virulence. No single factor predominated as the major predictor of virulence, their effects appearing to be cumulative. No combinations of the seven genes were either more or less likely to cause disease than others with the same number of virulence-associated genes. There was evidence of considerable horizontal transfer of genes on a background of clonality. Our findings also suggested that allelic variants of a polymorphic locus can make different contributions to the disease process, further study of which is likely to expand our understanding of staphylococcal disease pathogenesis.

scholarly journals Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children in Spain, 1990 to 2008

2011 ◽  
Vol 55 (5) ◽  
pp. 2297-2302 ◽  
Author(s):  
David Tarragó ◽  
Lorenzo Aguilar ◽  
Raquel García ◽  
María-José Gimenez ◽  
Juan-José Granizo ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Disease ◽  
Rapid Expansion ◽  
Reference Laboratory ◽  
Content Type ◽  
Lineal Regression ◽  
High Level ◽  
Susceptibility Profiles ◽  
Increasing Trends ◽  
Sequence Types

ABSTRACTThe genetic structure and antibiotic nonsusceptibility of all serotype 19AStreptococcus pneumoniaepediatric pneumococcal isolates received at the Spanish Pneumococcal Reference Laboratory (1990 to 2008) were analyzed. Of them, 410 (79.8%) isolates belonged to 14 sequence types (STs) with >10 isolates each, and 104 to 73 STs (with 21 new STs, ST5141 to ST5161, with one isolate each). Time trends in 2000 to 2008 (n= 471) were explored by lineal regression. Serotype 19A increased from 5.7% in 2000 to 16.8% in 2008 (R2= 0.872;P= 0.001). Decreasing trends (P< 0.03) were found for ST202 (R2= 0.774) and ST81 (R2= 0.559), and increasing trends (P< 0.03) for ST878 (R2= 0.544) and ST320 (R2= 0.530), both belonging to the clonal complex (CC) Denmark14-32 and first detected in 2003 and 2007, respectively, and ST2013 (R2= 0.704) and ST4461 (R2= 0.707), both appearing in 2004. Penicillin nonsusceptibility was clustered in ST81, ST276, ST320, ST878, ST2013, and ST4461 (>90% nonsusceptibility), and amoxicillin and cefotaxime nonsusceptibility in ST320: 87% amoxicillin (MIC50/MIC90= 8/8 μg/ml) and 43.5% cefotaxime (MIC50/MIC90= 1/2 μg/ml) nonsusceptibility. No trends were found for erythromycin nonsusceptibility (ranging from 38.5% to 66.7%) and cefotaxime nonsusceptibility (ranging from 0.0% to 7.8%), but increasing trends (P< 0.02) were found for oral penicillin (from 16.7% in 2000 to 56.3% in 2008;R2= 0.628) and amoxicillin (from 0.0% before 2007 to 13.8% in 2008;R2= 0.628) nonsusceptibility. This study warns about the emergence of serotype 19A STs associated with high-level antibiotic nonsusceptibility, with a role for ST320 and ST878 occupying the niche left by some pneumococcal 7-valent conjugate vaccine (PCV7)-related resistant STs. The rapid expansion of serotype 19A and STs related to antibiotic resistance indicates that vaccines covering serotype 19A present advantages in countering invasive disease.

Anatomical site-specific carbohydrate availability impacts Streptococcus pneumoniae virulence and fitness during colonization and disease

2021 ◽  
Author(s):  
Hansol Im ◽  
Katherine L. Kruckow ◽  
Adonis D’Mello ◽  
Feroze Ganaie ◽  
Eriel Martinez ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Disease Model ◽  
Invasive Disease ◽  
Relative Fitness ◽  
Anatomical Site ◽  
Virulence Determinants ◽  
Acid Fermentation ◽  
Altered Expression ◽  
Site Specific ◽  
Carbohydrate Availability

Streptococcus pneumoniae ( Spn ) colonizes the nasopharynx asymptomatically but can also cause severe life-threatening disease. Importantly, stark differences in carbohydrate availability exist between the nasopharynx and invasive disease sites, such as the bloodstream, which most likely impact Spn ’s behavior. Herein, using chemically-defined media (CDM) supplemented with physiological levels of carbohydrates, we examined how anatomical-site specific carbohydrate availability impacted Spn physiology and virulence. Spn grown in CDM modeling the nasopharynx (CDM-N) had reduced metabolic activity, slower growth rate, demonstrated mixed acid fermentation with marked H 2 O 2 production, and were in a carbon-catabolite repression (CCR)-derepressed state versus Spn grown in CDM modeling blood (CDM-B). Using RNA-seq, we determined the transcriptome for Spn WT and its isogenic CCR deficient mutant in CDM-N and CDM-B. Genes with altered expression as a result of changes in carbohydrate availability or catabolite control protein deficiency, respectively, were primarily involved in carbohydrate metabolism, but also encoded for established virulence determinants such polysaccharide capsule and surface adhesins. We confirmed that anatomical site-specific carbohydrate availability directly influenced established Spn virulence traits. Spn grown in CDM-B formed shorter chains, produced more capsule, were less adhesive, and were more resistant to macrophage killing in an opsonophagocytosis assay. Moreover, growth of Spn in CDM-N or CDM-B prior to the challenge of mice impacted relative fitness in a colonization and invasive disease model, respectively. Thus, anatomical site-specific carbohydrate availability alters Spn physiology and virulence, in turn promoting anatomical-site specific fitness.

scholarly journals Klebsiella pneumoniae with capsule type K64 is overrepresented among invasive disease in Vietnam

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 454
Author(s):  
Bich Vu Thi Ngoc ◽  
Sylvain Brisse ◽  
Trinh Dao Tuyet ◽  
Dung Vu Tien Viet ◽  
Kathryn E Holt ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Susceptibility Testing ◽  
Invasive Disease ◽  
Community Acquired Pneumonia ◽  
Capsule Type ◽  
Carbapenem Resistant ◽  
Rural And Urban ◽  
Significant Difference ◽  
Invasive Infections ◽  
Sequence Types

Introduction: Recent reports indicate the emergence of community-acquired pneumonia associated with K64-Klebsiella pneumoniae. Here, we identify the capsular types and sequence type of invasive and commensal K. pneumoniae isolates from Vietnam. Methods: We included 93 K. pneumoniae isolates from patients hospitalized at the National Hospital for Tropical Diseases, Hanoi between 2007 and 2011; and 110 commensal isolates from throat swabs from healthy volunteers living in rural and urban Hanoi in 2012. We determined sequence types (STs) by multi-locus sequence typing (MLST) and capsule typing for seven K types by PCR. Antibiotic susceptibility testing was performed using disk diffusion. Results: The most common detected capsule types were K1 (39/203, 19.2%, mainly ST23) and K2 (31/203, 15.3%, multiple STs: ST65, ST86, ST380). We found significantly more K2 isolates among invasive in comparison to commensal isolates (22.6% vs 9%, p = 0.01) but no significant difference was observed between invasive and commensal K1 isolates (14.5% vs 24.7%, p = 0.075). K64 with varying sequence types were predominantly seen among invasive K. pneumoniae (8 vs. 3) and were isolated from sepsis and meningitis patients. Among K64 isolates, one was carbapenem-resistant with ST799. Conclusion: Our study confirms that capsule type K64 K. pneumoniae is associated with community-acquired invasive infections in Vietnam. Research is needed to unravel the mechanisms of virulence of capsule type K64 in both community and hospital settings.

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