scholarly journals Immunization with a Combination of Three Pneumococcal Proteins Confers Additive and Broad Protection against Streptococcus pneumoniae Infections in Mice

2009 ◽  
Vol 78 (3) ◽  
pp. 1276-1283 ◽  
Author(s):  
Kaifeng Wu ◽  
Xuemei Zhang ◽  
Jing Shi ◽  
Nan Li ◽  
Dairong Li ◽  
...  

ABSTRACT Pneumococcal polysaccharide-based vaccines are effective in preventing pneumococcus infection; however, some drawbacks preclude their widespread use in developing and undeveloped countries. Here, we evaluated the protective effects of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (ΔA146 Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), the most striking protection was obtained with the combination of the three antigens. Similarly, with the intranasal challenge models, (i) additive clearance of bacteria in lungs was observed for the combination of the three antigens and (ii) a combination vaccine conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80% protection for pneumococcal strain 6B. Even so, immunity to this combination could confer protection against pneumococcal infection with a mixture of four serotypes. Our results showed that the combination vaccine was as effective as the currently used vaccines (PCV7 and PPV23). These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models.

Author(s):  
Bekele Sharew ◽  
Feleke Moges ◽  
Gizachew Yismaw ◽  
Wondwossen Abebe ◽  
Surafal Fentaw ◽  
...  

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.


2020 ◽  
Author(s):  
BEKELE SHAREW ◽  
Feleke Moges ◽  
Gizachew Yismaw ◽  
Wondiwossen Abebe ◽  
Surafal Fentaw ◽  
...  

Abstract Backgrounds: Streptococcus pneumoniae is one of the leading causes of bacterial meningitis and pneumoniae in elderly people and children. Antimicrobial resistant strains of Streptococcus pneumoniae has been detected in all parts of the world and become one of the greatest challenges to global public health today. The aim of this study is therefore, to assess the antimicrobial resistance profiles and multidrug resistance patterns of S. pneumoniae isolates from patients suspected for pneumococcal infections in Ethiopia. Methods: A hospital-based prospective study was conducted from 2018 to 2019 at Addis Ababa and Amhara region referral hospitals. Antimicrobial resistance tests were performed on 57 isolates of S. pneumoniae that were collected from pediatric and adult patients. Samples (cerebrospinal fluid, blood, sputum, eye discharge, ear discharge, pleural and peritoneal fluids) from all collection sites were initially cultured onto 5 % sheep blood agar plates and incubated overnight at 370C in 5% CO2 atmosphere. S. 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 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. 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 bacterial 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 a number of commonly used antibiotics including penicillin. Hence, it is important to periodically monitor the antibiotic resistance patterns to choose empirical treatments for better management of pneumococcal infection.


2019 ◽  
Author(s):  
Kimberly McCullor ◽  
Maliha Rahman ◽  
Catherine King ◽  
W. Michael McShan

AbstractPhage-like elements are found in a multitude of streptococcal species, including pneumococcal strain Hungary19A-6 (SpnCI). The aim of our research was to investigate the role of phage-like element SpnCI in enhanced virulence and phenotypic modulation within Streptococcus pneumoniae. SpnCI was found to significantly enhance virulence within the invertebrate infection model Galleria mellonella. Infections with SpnCI led to a lower mean health score (1.6) and survival percentage (20%) compared to SpnCI null TIGR4 infections (3.85 mean health score and 50% survival). SpnCI remained integrated throughout growth, conferring greater sensitivity to UV irradiation. Change in transcriptional patterns occurred, including downregulation of operons involved with cell surface modelling in the SpnCI containing strain of TIGR4. Kanamycin-tagged SpnCI strain in Hungary19A-6 was inducible and isolated from lysate along with both annotated prophages. No phages were identified by PCR nor electron microscopy (EM) following induction of TIGR4 SpnCIΔstrA suggesting helper-phage dependence for dissemination. EM of lysate showed typical siphoviridae morphology with an average capsid size of 60 nm. Two of sixty capsids were found to be smaller, suggesting SpnCI disseminates using a similar mechanism described for Staphylococcus aureus phage-like element SaPI. SpnCI from lysate infected capsule null strain T4R but was incapable of infecting the encapsulated TIGR4 strain suggesting that capsule impedes phage infection. Our work demonstrates that SpnCI can modulate virulence, UV susceptibility, alter transcriptional patterns, and furthermore, can disseminate via infection within pneumococcus. Further research is necessary to elucidate how SpnCI modulates virulence and what genes are responsible for the enhanced virulence phenotype.ImportanceAlthough vaccines have limited the scope of pneumococcal infections, Streptococcus pneumoniae still remains an important human pathogen. Understanding novel elements, such as SpnCI, that enhance virulence can lead to the development of more targeted therapeutic and diagnostic tools within the clinical realm.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3321-3321
Author(s):  
Lynn Weber ◽  
Charlet A. Allen ◽  
Patricia Ackerman ◽  
Yoav Messinger

Abstract Invasive pneumococcal infections can be devastating in the setting of immune deficiency. These infections have been seen in pediatric oncology practices, but the outcome has not been reported. With the introduction of routine 7- valent pneumococcal conjugate vaccine (PCV7) the rate of pneumococcal infections dramatically decreased in the general pediatric population. It is unclear if a similar reduction in rate would be seen in pediatric oncology patients. A total of 44 pneumococcal infections occurred in 34 oncology patients at Childrens Hospital and Clinics of Minnesota over a 5-year period (5/1/2001 – 4/30/2006). Twenty-five episodes of invasive infection were identified in 24 patients, of which 4 (16.7%) required intensive care admissions and 2 of them died (8.3%). During this period 863 new malignancies were diagnosed, therefore our rate of invasive infection is estimated to be 28 per 1000 oncology patients. This is higher than the reported rate of 3.8 8.1 infections per 1000 stem cell transplantation patients. Fifteen patients (62%) with invasive infections were diagnosed with leukemia, of which 12 had acute lymphoblastic leukemia. The invasive infections occurred a median of 15.2 months (range 0–36) after diagnosis and the median patient age at time of infection was 5.6 years (range 1.5 - 14). The average length of hospitalization for patients was 8.3 days (range 0–38), with six patients receiving outpatient therapy alone. Pneumococcal serotypes were known in 21 of the 25 episodes of invasive pneumococcal infection and in 1 non-invasive infection. Of the 22 serotypes identified, 19 were covered by either PCV7 or the 23-valent pneumococcal polysaccharide vaccine (PS23). Eleven patients who were immunized with either PCV7 or PS23 later developed a pneumococcal strain that should have been covered by the immunization. Three patients who received immunization acquired a strain of streptococcus pneumoniae not included in either vaccine. Invasive pneumococcal infection is a potentially preventable complication with a high morbidity and mortality. Use of PCV7 or PS23 may not prevent the development of pneumococcal infection in pediatric oncology patients with vaccine-susceptible strains. It is unclear whether immunization before and during the immunocompromised period results in protective immunity against streptococcus pneumoniae.


2003 ◽  
Vol 41 (143) ◽  
pp. 397-400
Author(s):  
Basudha Koirala ◽  
S K Sharma ◽  
M Deb ◽  
S K Bhatttacharya

Seventy-one isolates of Streptococcus pneumoniae were obtained from various clinicalspecimens of sixty-six patients. Type of pneumococcal infections varied in differentage groups. Major brunt of the invasive pneumococcal infection was borne by infantsand children. Isolates from infected corneal ulcers were relatively resistant toantimicrobials including penicillin, as compared to those isolated from normallysterile body sites.Key Words: Pneumoccoccal infection, antimicrobial susceptibility, Eastern Nepal.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jae Soo Kim ◽  
Bo Kyeung Jung ◽  
Jong Wan Kim ◽  
Ga Yeon Kim

Pneumococcal infection is the main causative agent of pneumonia, meningitis, and sepsis in immunocompromised and elderly people. The samples in this study were collected from subjects in an 800-bed hospital in Chungnam province, Korea, over the past 8 years. Of the 473,230 samples obtained for microbial culture from 2012 to 2019, Streptococcus pneumoniae was isolated from 714 samples collected from 702 patients, with a pneumococcal-positive rate of 0.15%. We investigated the temporal, demographic, and specimen-specific distributions, as well as the antibiotic susceptibility pattern for S. pneumonia. The age of patients ranged from 0 days to 98 years, with an average age of 64.7 years. The distribution among the sexes was 2.4 : 1 (male : female), with more samples isolated from male patients. We observed that spring was the predominant season in which the infection occurred, accounting for 37.6% of the cases. Pneumococci were most frequently isolated from sputum (608 cases, 85.2%). Invasive infections were detected at a rate of 66% (in blood cultures), and noninvasive infections were detected at a rate of 91% (in sputum cultures). Antimicrobial resistance to ceftriaxone, cefotaxime, erythromycin, tetracycline, clindamycin, cotrimoxazole, levofloxacin, and penicillin, based on noninvasive infections, was observed in 21.6%, 27.2%, 79.2%, 73.2%, 68.0%, 51.3%, 9.8%, and 18.1% of cases, respectively. Additionally, on average, 66.9% of multidrug-resistant bacteria showed resistance to three or more antimicrobial agents, and 2.8% showed resistance to all other antibacterial agents except vancomycin. These results might facilitate the administration of appropriate empirical antibacterial therapy for pneumococcal infections.


2020 ◽  
Author(s):  
BEKELE SHAREW ◽  
Feleke Moges ◽  
Gizachew Yismaw ◽  
Wondiwossen Abebe ◽  
Surafal Fentaw ◽  
...  

Abstract Background Streptococcus pneumoniae is one of the leading causes of bacterial meningitis and pneumonia in elderly people and children. Antimicrobial-resistant strains of Streptococcus pneumoniae have been detected in all parts of the world and have become one of the greatest challenges to global public health today. 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 2018 to 2019 at Addis Ababa and Amhara region referral hospitals. Antimicrobial resistance tests were performed on 57 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 370C in a 5% CO2 atmosphere. S. 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 bacterial 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 antibiotic resistance patterns to choose empirical treatments for better management of pneumococcal infection.


2019 ◽  
Vol 9 (2) ◽  
pp. 229-238
Author(s):  
S. Yu. Tereshchenko ◽  
M. V. Smolnikova

Here we review currently available data showing that innate immune signs predisposing to recurrent and invasive pneumococcal infections were identified in children. Streptococcus pneumoniae (pneumococcus) belongs to Grampositive bacteria being the major cause of morbidity and mortality in infants, especially in developing countries and in communities with low socioeconomic status. Due to the lack of anti-pneumococcal vaccination, the significant proportion of pneumococcus carriers develop non-invasive (pneumonia, otitis media, sinusitis) and severe invasive (bacteremia/septicemia, meningitis) pneumococcal infection. A great deal of diverse factors related to pneumococcus biological features (virulence factors) as well individualized host-specific immunity are implicated in efficient bacterial penetration across the mucous membranes. The TLR signaling system plays a crucial role in the human nonspecific defense upon the first encounter with the pathogen. Various TLRs comprise the first pattern recognition receptor fami ly ever described which sense ligands derived from the outer bacterial wall. The complement system is the ancient innate immunity component mainly involved in intravascular elimination of bacterial agents. In addition, the complement proteins serve as a bridge between innate and adaptive immunity, ensuring optimal conditions for B- and T-cell maturation and differentiation. Because pneumococcus secretes the IgA protease, a local protective effects related to IgA antibodies might not be so prominent. Therefore, B-cell immunodeficiency and impaired complement system hold a lead place among congenital causes resulting in severe and recurrent pneumococcal infections in children. Thus, based on available data, we concluded that impaired B-cell function, the complement components deficiency as well as receptor-recognition receptors (TLR-2, -9, -4, MYD88 adapter protein, TLR cascade enzymes: IRAK4, NEMO, NOD-like receptors: NOD2, NLRP3; C-type lectins: MBL, Dextin-2, and, possibly, ficoline) play the most important role among congenital immunodeficiencies predisposing to invasive and recurrent pneumococcal infections play the most important role among congenital immunodeficiencies predisposing to invasive and recurrent pneumococcal infections, and should be used as a rationale for immunological surveillance and organizing immunogenetics screening in these patients.  


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

2021 ◽  
Vol 9 (6) ◽  
pp. 1324
Author(s):  
Fernanda Raya Tonetti ◽  
Mikado Tomokiyo ◽  
Ramiro Ortiz Moyano ◽  
Sandra Quilodrán-Vega ◽  
Hikari Yamamuro ◽  
...  

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.


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