scholarly journals Evaluation of Biophotonic Imaging To Estimate Bacterial Burden in Mice Infected with Highly Virulent Compared to Less Virulent Streptococcus pneumoniae Serotypes

2010 ◽  
Vol 54 (8) ◽  
pp. 3155-3160 ◽  
Author(s):  
Stefanie Henken ◽  
Jennifer Bohling ◽  
A. David Ogunniyi ◽  
James C. Paton ◽  
Vyvyan C. Salisbury ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Disease Progression ◽  
Bacterial Infections ◽  
Pneumococcal Disease ◽  
Bioluminescence Imaging ◽  
Disease Model ◽  
Real Life ◽  
Laboratory Animals ◽  
Mouse Strains ◽  
Biophotonic Imaging

ABSTRACT Bioluminescence imaging is an innovative, noninvasive tool to analyze infectious disease progression under real-life conditions in small laboratory animals. However, the relevance of bioluminescence imaging to monitor invasive compared to noninvasive bacterial infections of the lung has not been examined so far. In the current study, we systematically evaluated the importance of bioluminescence imaging to monitor pneumococcal disease progression by correlating biophotonic signals with lung bacterial loads in two mouse strains (BALB/c, C57BL/6) infected with either self-glowing, bioluminescent serotype 19 Streptococcus pneumoniae causing focal pneumonia or serotype 2 S. pneumoniae causing invasive pneumococcal disease. The best correlations between bioluminescence signals and lung CFU counts were observed in BALB/c mice compared to C57BL/6 mice just on day 3 after infection with invasive serotype 2 S. pneumoniae, while excellent correlations between photon counts and bacterial loads were observed in isolated lungs of BALB/c and C57BL/6 mice, irrespective of the employed pneumococcal serotype. Moreover, good correlations between biophotonic signals and CFU counts were also observed in mice upon infection with serotype 19 S. pneumoniae causing focal pneumonia in mice, again with best correlation values obtained for BALB/c mice at day 3 postinfection. Collectively, we show that the relevance of biophotonic imaging to monitor S. pneumoniae-induced lung infections in mice is largely influenced by the disease model under investigation. The provided data may be important for studies of infectious diseases.

scholarly journals Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

2016 ◽  
Vol 84 (5) ◽  
pp. 1536-1547 ◽  
Author(s):  
Pamela Shen ◽  
Mathieu C. Morissette ◽  
Gilles Vanderstocken ◽  
Yang Gao ◽  
Muhammad Hassan ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Cigarette Smoke ◽  
Invasive Pneumococcal Disease ◽  
Bacterial Infections ◽  
Pneumococcal Disease ◽  
Pneumococcal Infection ◽  
Cigarette Smoke Exposure ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Pneumococcal Colonization

Streptococcus pneumoniaeis a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.

scholarly journals Efficacy Profiles of Daptomycin for Treatment of Invasive and Noninvasive Pulmonary Infections with Streptococcus pneumoniae

2009 ◽  
Vol 54 (2) ◽  
pp. 707-717 ◽  
Author(s):  
Stefanie Henken ◽  
Jennifer Bohling ◽  
Jens Martens-Lobenhoffer ◽  
James C. Paton ◽  
A. David Ogunniyi ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Disease ◽  
Pneumococcal Pneumonia ◽  
Therapeutic Option ◽  
Severe Pneumonia ◽  
Therapeutic Value ◽  
Excellent Activity ◽  
Biophotonic Imaging ◽  
Life Threatening ◽  
Lipopeptide Antibiotic

ABSTRACT Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ∼70% or ∼60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.

scholarly journals Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Masahide Yano ◽  
Shruti Gohil ◽  
J. Robert Coleman ◽  
Catherine Manix ◽  
Liise-anne Pirofski
Keyword(s):  
Monoclonal Antibodies ◽  
Streptococcus Pneumoniae ◽  
Quorum Sensing ◽  
Direct Effect ◽  
Pneumococcal Disease ◽  
Effector Cell ◽  
Capsular Polysaccharide ◽  
Genetic Exchange ◽  
Content Type ◽  
Specific Antibodies

ABSTRACTThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two differentStreptococcus pneumoniaeserotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotypeinvitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.IMPORTANCECurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology ofStreptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

scholarly journals Assignment of Weight-Based Immunoglobulin G1 (IgG1) and IgG2 Units in Antipneumococcal Reference Serum Lot 89-S(F) for Pneumococcal Polysaccharide Serotypes 1, 4, 5, 7F, 9V, and 18C

2005 ◽  
Vol 12 (1) ◽  
pp. 218-223 ◽  
Author(s):  
Daniel J. Sikkema ◽  
Nancy A. Ziembiec ◽  
Thomas R. Jones ◽  
Stephen W. Hildreth ◽  
Dace V. Madore ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Disease ◽  
Pneumococcal Infection ◽  
Capsular Polysaccharides ◽  
Standardization Method ◽  
Igg2 Antibody ◽  
Reference Serum

ABSTRACT Weight-based assignments for immunoglobulin G1 (IgG1) and IgG2 subclass antibodies to Streptococcus pneumoniae capsular polysaccharides (PnPs) in antipneumococcal standard reference serum lot 89-S (lot 89-S), also known as lot 89-SF, have been determined for serotypes 1, 4, 5, 7F, 9V, and 18C. This extends the usefulness of lot 89-S beyond the IgG1 and IgG2 subclass assignments for serotypes 3, 6B, 14, 19F, and 23F made previously (A. Soininen, H. Kayhty, I. Seppala, and T. Wuorimaa, Clin. Diagn. Lab. Immunol. 5:561-566, 1998) to cover 11 major serotypes associated with the highest percentage of pneumococcal disease worldwide. A method of equivalence of absorbances in enzyme immunosorbent assays was used to determine the IgG1 and IgG2 antibody concentrations for the additional serotypes in lot 89-S, based on the subclass values previously assigned for PnPs serotypes 6B, 14, and 23F. This cross-standardization method assures consistency with previous antibody assignments in that reference serum. The newly assigned subclass values for serotype 9V, and previously assigned values for serotype 14, were used to quantitate PnPs antibodies in sera from adult and pediatric subjects immunized with a pneumococcal conjugate vaccine. There was a predominance of IgG1 anti-PnPs antibodies in pediatric sera and IgG2 anti-PnPs antibodies in the adult sera. The IgG1 and IgG2 subclass assignments for the 11 PnPs serotypes in antipneumococcal standard reference serum lot 89-S are useful for quantitating and characterizing immune responses to pneumococcal infection and vaccination regimens.

scholarly journals An Uncommon Site of Streptococcus pneumoniae Colonization Leading to Recurrent Pneumococcal Disease

2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Parham Sendi ◽  
Eva Maria Moser Schaub ◽  
Konstantinos Nirgianakis ◽  
Lucy J. Hathaway ◽  
Pascal Bittel ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Vaccine ◽  
Pneumococcal Disease ◽  
Contraceptive Device ◽  
Source Of Infection ◽  
Vaginal Colonization ◽  
Intrauterine Contraceptive ◽  
Conjugate Pneumococcal Vaccine ◽  
Antibody Levels

Abstract This report describes a case of relapsing pneumococcal peritonitis. The postulated source of infection was vaginal colonization and secondary adherence of pneumococci to an intrauterine contraceptive device. After immunization with a conjugate pneumococcal vaccine, her antibody levels were observed. She remained infection free at the 2-year follow-up investigation.

scholarly journals Evaluating post-vaccine expansion patterns of pneumococcal serotypes

2020 ◽  
Author(s):  
Maile T. Phillips ◽  
Joshua L. Warren ◽  
Noga Givon-Lavi ◽  
Adrienn Tothpal ◽  
Gili Regev-Yochay ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Pneumococcal Disease ◽  
Jewish Population ◽  
Pneumococcal Disease ◽  
Pneumococcal Serotypes ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines ◽  
Vaccine Serotypes ◽  
Serotype Replacement ◽  
Disease Understanding

ABSTRACTStreptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.

scholarly journals Invasive isolates of Streptococcus pneumoniae in Serbia: Antimicrobial susceptibility and serotypes

2013 ◽  
Vol 141 (1-2) ◽  
pp. 48-53 ◽  
Author(s):  
Ina Gajic ◽  
Vera Mijac ◽  
Lazar Ranin ◽  
Dragana Andjelkovic ◽  
Miroslava Radicevic ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Pneumococcal Disease ◽  
Antimicrobial Susceptibility ◽  
Pneumococcal Disease ◽  
Medical Problem ◽  
Resistance Rate ◽  
Reference Laboratory ◽  
Susceptibility Pattern ◽  
Antimicrobial Susceptibility Pattern ◽  
Resistance Rates

Introduction. Streptococcus pneumoniae is one of the leading causes of bacterial meningitis and sepsis. Invasive pneumococcal disease is a significant medical problem worldwide, particularly in children, due to a huge increase of pneumococcal resistance to antibiotics. Objective. The aim of the study was to investigate the antimicrobial susceptibility pattern of invasive pneumococcal isolates, as well as to determine whether decreased S. pneumoniae susceptibility to antibiotics was related to a particular serotype. Methods. Antimicrobial susceptibility to 19 antibiotics was determined in 58 invasive pneumococcal strains that were collected from seven regional centers during the period July 2009 to February 2011 in the National Reference Laboratory for streptococci and pneumococci. Results. The overall nonsusceptibility rate to penicillin was detected in 34% of pneumococcal isolates and to erythromycin in 36%. Higher resistance rates were observed among children than among adults. Penicillin resistance rate was 65% in children versus 22% in adults, while erythromycin nonsusceptibility rate was 47% in children versus 32% in adults. Co-resistance to penicillin and erythromycin was detected in 21% strains, mostly isolated from children. Multiresistance was found in one third of isolates. All strains were susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin, while 23 (40%) isolates were susceptible to all tested antibiotics. The most common resistant serotypes were 19F and 14. Conclusion. The study has revealed that penicillin and macrolide resistance among invasive pneumococcal isolates is very high in Serbia. This emphasizes the need for continuous monitoring for invasive pneumococcal disease to document the serotype distribution and antimicrobial susceptibility pattern.

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