scholarly journals SEROTYPE-INDEPENDENT VACCINES AGAINST PNEUMOCOCCAL INFECTION

2016 ◽  
pp. 76-85
Author(s):  
I. B. Semenova ◽  
N. A. Mikhailova
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Mechanism Of Action ◽  
Aluminium Hydroxide ◽  
Pneumococcal Infection ◽  
Human Organism ◽  
Preclinical Studies ◽  
Vaccine Preparation ◽  
Protein Vaccines ◽  
Selection Of

Creation of serotype-independent vaccines includes 4 directions - construction of protein vaccines based on recombinant pneumococcus proteins, whole-cell killed or attenuated vaccines, DNA-vaccines and use of Streptococcus pneumoniae as a carrier for polysaccharide and conjugated vaccine preparations. Protein vaccines are the most widely studied. Around 20 proteins are described for pneumococcus - intracellular, associated with cell wall and secreted. The majority of researchers stop at construction of a vaccine preparation including a set of several proteins, protecting from colonization, invasion, pneumonia. Mechanism of action for protein vaccines differs from that of polysaccharide vaccines. Protein preparations create protection from several pneumococcus serotypes. Study of cross-activity of protein-candidates for vaccine preparations with human organism tissues is actual for preclinical studies. Selection of adjuvants is necessary for these vaccines, because aluminium hydroxide is not a suitable adjuvant for these preparations.

scholarly journals C-reactive protein is protective against Streptococcus pneumoniae infection in mice.

1981 ◽  
Vol 154 (5) ◽  
pp. 1703-1708 ◽  
Author(s):  
C Mold ◽  
S Nakayama ◽  
T J Holzer ◽  
H Gewurz ◽  
T W Du Clos
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
C Reactive Protein ◽  
Reactive Protein

C-reactive protein (CRP) has several properties that suggest that it may function as a bacterial opsonin. CRP shows binding reactivity with pneumococcal C-polysaccharide, the cell wall carbohydrate of Streptococcus pneumoniae. In this study we have demonstrated protection of mice against serotypes 3 and 4 of S. pneumoniae infection by a single prior injection of CRP. This effect was seen both in mice that lacked antibody to phosphocholine and in normal mice. Thus the opsonic properties of CRP previously described may be related to protection against pneumococcal infection.

DiiA is a novel dimorphic cell wall protein of Streptococcus pneumoniae involved in invasive disease

2016 ◽  
Vol 73 (1) ◽  
pp. 71-81 ◽  
Author(s):  
María S. Escolano-Martínez ◽  
Arnau Domenech ◽  
José Yuste ◽  
María I. Cercenado ◽  
Carmen Ardanuy ◽  
...  
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Invasive Disease ◽  
Cell Wall Protein

scholarly journals Antimicrobial resistance profile and multidrug resistance patterns of Streptococcus pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Bekele Sharew ◽  
Feleke Moges ◽  
Gizachew Yismaw ◽  
Wondwossen Abebe ◽  
Surafal Fentaw ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Resistance ◽  
Addis Ababa ◽  
Pneumococcal Infection ◽  
Test Method ◽  
Resistance Testing ◽  
Global Public Health ◽  
Pneumococcal Infections ◽  
Resistance Patterns

Abstract Background Antimicrobial-resistant strains of Streptococcus pneumoniae have become one of the greatest challenges to global public health today and inappropriate use of antibiotics and high level of antibiotic use is probably the main factor driving the emergence of resistance worldwide. The aim of this study is, therefore, to assess the antimicrobial resistance profiles and multidrug resistance patterns of S. pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia. Methods A hospital-based prospective study was conducted from January 2018 to December 2019 at Addis Ababa city and Amhara National Region State Referral Hospitals. Antimicrobial resistance tests were performed from isolates of S. pneumoniae that were collected from pediatric and adult patients. Samples (cerebrospinal fluid, blood, sputum, eye discharge, ear discharge, and pleural and peritoneal fluids) from all collection sites were initially cultured on 5% sheep blood agar plates and incubated overnight at 37 °C in a 5% CO2 atmosphere. Streptococcus pneumoniae was identified and confirmed by typical colony morphology, alpha-hemolysis, Gram staining, optochin susceptibility, and bile solubility test. Drug resistance testing was performed using the E-test method according to recommendations of the Clinical and Laboratory Standards Institute. Results Of the 57 isolates, 17.5% were fully resistant to penicillin. The corresponding value for both cefotaxime and ceftriaxone was 1.8%. Resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole were 59.6%, 17.5%, 38.6%, 17.5 and 24.6%, respectively. Multidrug resistance (MDR) was seen in 33.3% isolates. The most common pattern was co-resistance to penicillin, erythromycin, clindamycin, and tetracycline. Conclusions Most S. pneumoniae isolates were susceptible to ceftriaxone and cefotaxime. Penicillin has been used as a drug of choice for treating S. pneumoniae infection. However, antimicrobial resistance including multidrug resistance was observed to several commonly used antibiotics including penicillin. Hence, it is important to periodically monitor the antimicrobial resistance patterns to select empirical treatments for better management of pneumococcal infection.

scholarly journals Streptococcus pneumoniae Serotype-2 Childhood Meningitis in Bangladesh: A Newly Recognized Pneumococcal Infection Threat

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32134 ◽  
Author(s):  
Samir K. Saha ◽  
Hassan M. Al Emran ◽  
Belal Hossain ◽  
Gary L. Darmstadt ◽  
Senjuti Saha ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection

scholarly journals The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

2021 ◽  
Vol 9 (6) ◽  
pp. 1324
Author(s):  
Fernanda Raya Tonetti ◽  
Mikado Tomokiyo ◽  
Ramiro Ortiz Moyano ◽  
Sandra Quilodrán-Vega ◽  
Hikari Yamamuro ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Innate Immune Response ◽  
Pneumococcal Infection ◽  
Innate Immune ◽  
Nasal Administration ◽  
Commensal Bacterium ◽  
Beneficial Effects ◽  
Immunological Mechanisms ◽  
Immunomodulatory Properties

Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

scholarly journals Structural and Functional Insights into Peptidoglycan Access for the Lytic Amidase LytA of Streptococcus pneumoniae

mBio ◽  
2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Peter Mellroth ◽  
Tatyana Sandalova ◽  
Alexey Kikhney ◽  
Francisco Vilaplana ◽  
Dusan Hesek ◽  
...  
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Solution Structure ◽  
Substrate Binding ◽  
Substrate Recognition ◽  
Lytic Activity ◽  
Site Directed Mutagenesis ◽  
Binding Motif ◽  
Content Type ◽  
Peptidoglycan Synthesis

ABSTRACT The cytosolic N-acetylmuramoyl-l-alanine amidase LytA protein of Streptococcus pneumoniae, which is released by bacterial lysis, associates with the cell wall via its choline-binding motif. During exponential growth, LytA accesses its peptidoglycan substrate to cause lysis only when nascent peptidoglycan synthesis is stalled by nutrient starvation or β-lactam antibiotics. Here we present three-dimensional structures of LytA and establish the requirements for substrate binding and catalytic activity. The solution structure of the full-length LytA dimer reveals a peculiar fold, with the choline-binding domains forming a rigid V-shaped scaffold and the relatively more flexible amidase domains attached in a trans position. The 1.05-Å crystal structure of the amidase domain reveals a prominent Y-shaped binding crevice composed of three contiguous subregions, with a zinc-containing active site localized at the bottom of the branch point. Site-directed mutagenesis was employed to identify catalytic residues and to investigate the relative impact of potential substrate-interacting residues lining the binding crevice for the lytic activity of LytA. In vitro activity assays using defined muropeptide substrates reveal that LytA utilizes a large substrate recognition interface and requires large muropeptide substrates with several connected saccharides that interact with all subregions of the binding crevice for catalysis. We hypothesize that the substrate requirements restrict LytA to the sites on the cell wall where nascent peptidoglycan synthesis occurs. IMPORTANCE Streptococcus pneumoniae is a human respiratory tract pathogen responsible for millions of deaths annually. Its major pneumococcal autolysin, LytA, is required for autolysis and fratricidal lysis and functions as a virulence factor that facilitates the spread of toxins and factors involved in immune evasion. LytA is also activated by penicillin and vancomycin and is responsible for the lysis induced by these antibiotics. The factors that regulate the lytic activity of LytA are unclear, but it was recently demonstrated that control is at the level of substrate recognition and that LytA required access to the nascent peptidoglycan. The present study was undertaken to structurally and functionally investigate LytA and its substrate-interacting interface and to determine the requirements for substrate recognition and catalysis. Our results reveal that the amidase domain comprises a complex substrate-binding crevice and needs to interact with a large-motif epitope of peptidoglycan for catalysis.

Microbial exposure early in life regulates airway inflammation in mice after infection with Streptococcus pneumoniae with enhancement of local resistance

2010 ◽  
Vol 298 (1) ◽  
pp. L67-L78 ◽  
Author(s):  
Yasuki Yasuda ◽  
Yoko Matsumura ◽  
Kazuki Kasahara ◽  
Noriko Ouji ◽  
Shigeki Sugiura ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
Hygiene Hypothesis ◽  
Respiratory Pathogen ◽  
T Helper 1 ◽  
Innate Resistance ◽  
Anaerobic Microorganisms ◽  
Early Life Exposure ◽  
Microbial Extracts ◽  
Microbial Exposure

The immunological explanation for the “hygiene hypothesis” has been proposed to be induction of T helper 1 (Th1) responses by microbial products. However, the protective results of hygiene hypothesis-linked microbial exposures are currently shown to be unlikely to result from a Th1-skewed response. Until now, effect of microbial exposure early in life on airway innate resistance remained unclear. We examined the role of early life exposure to microbes in airway innate resistance to a respiratory pathogen. Specific pathogen-free weanling mice were nasally exposed to the mixture of microbial extracts or PBS (control) every other day for 28 days and intratracheally infected with Streptococcus pneumoniae 10 days after the last exposure. Exposure to microbial extracts facilitated colonization of aerobic gram-positive bacteria, anaerobic microorganisms, and Lactobacillus in the airway, compared with control exposure. In pneumococcal pneumonia, the exposure prolonged mouse survival days by suppressing bacterial growth and by retarding pneumococcal blood invasion, despite significantly low levels of leukocyte recruitment in the lung. Enhancement of airway resistance was associated with a significant decrease in production of leukocyte chemokine (KC) and TNFα, and suppression of matrix metalloproteinase (MMP-9) expression/activation with enhancement of tissue inhibitor of MMP (TIMP-3) activation. The exposure increased production of IFN-γ, IL-4, and monocyte chemoattractant-1 following infection. Furthermore, expression of Toll-like receptor 2, 4, and 9 was promoted by the exposure but no longer upregulated upon pneumococcal infection. Thus, we suggest that hygiene hypothesis is more important in regulating the PMN-dominant inflammatory response than in inducing a Th1-dominant response.

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