scholarly journals RNA thermosensors facilitate Streptococcus pneumoniae and Haemophilus influenzae immune evasion

2021 ◽  
Vol 17 (4) ◽  
pp. e1009513
Author(s):  
Hannes Eichner ◽  
Jens Karlsson ◽  
Laura Spelmink ◽  
Anuj Pathak ◽  
Lok-To Sham ◽  
...  

Bacterial meningitis is a major cause of death and disability in children worldwide. Two human restricted respiratory pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are the major causative agents of bacterial meningitis, attributing to 200,000 deaths annually. These pathogens are often part of the nasopharyngeal microflora of healthy carriers. However, what factors elicit them to disseminate and cause invasive diseases, remain unknown. Elevated temperature and fever are hallmarks of inflammation triggered by infections and can act as warning signals to pathogens. Here, we investigate whether these respiratory pathogens can sense environmental temperature to evade host complement-mediated killing. We show that productions of two vital virulence factors and vaccine components, the polysaccharide capsules and factor H binding proteins, are temperature dependent, thus influencing serum/opsonophagocytic killing of the bacteria. We identify and characterise four novel RNA thermosensors in S. pneumoniae and H. influenzae, responsible for capsular biosynthesis and production of factor H binding proteins. Our data suggest that these bacteria might have independently co-evolved thermosensing abilities with different RNA sequences but distinct secondary structures to evade the immune system.

2019 ◽  
Author(s):  
Hannes Eichner ◽  
Laura Spelmink ◽  
Anuj Pathak ◽  
Birgitta Henriques-Normark ◽  
Edmund Loh

AbstractBacterial meningitis is a major cause of death and disability in children worldwide. Two human restricted pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are the major causative agents of bacterial meningitis, attributing to 200,000 deaths annually. These pathogens are often part of the nasopharyngeal microflora of healthy carriers. However, what factors elicit them to disseminate and cause invasive diseases remain unknown. Elevated temperature and fever are hallmarks of inflammation triggered by infections and can act as warning signal to these pathogens. Here, we investigate whether these pathogens could sense environmental temperature to evade host complement-mediated killing. We show that expression of two vital virulence factors and vaccine components, the capsule and factor H binding proteins, are temperature dependent. We identify and characterize four novel RNA thermosensors in S. pneumoniae and H. influenzae within their 5′-untranslated regions of genes, responsible for capsular biosynthesis and production of factor H binding proteins. Our data further demonstrate that these pathogens have co-evolved thermosensing abilities independently with unique RNA sequences, but distinct secondary structures, to evade the human immune system.Author SummaryStreptococcus pneumoniae and Haemophilus influenzae are bacteria that reside in the upper respiratory tract. This harmless colonization may progress to severe and often lethal septicaemia and meningitis, but molecular mechanisms that control why these pathogens invade the circulatory system remain largely unknown. Here we show that both S. pneumoniae and H. influenzae can evade complement killing by sensing the temperature of the host. We identify and characterize four novel RNA thermosensors in S. pneumoniae and H. influenzae within their respective 5′-untranslated regions of genes, influencing capsular biosynthesis and production of factor H binding proteins. Moreover, we show that these RNA thermosensors evolved independently with exclusive unique RNA sequences to sense the temperature in the nasopharynx and in other body sites to avoid immune killing. Our finding that regulatory RNA senses temperatures and directly regulate expression of two important virulence factors and vaccine components of S. pneumoniae and H. influenzae, is most important for our understanding of bacterial pathogenesis and for vaccine development. Our work could pave the way for similar studies in other important bacterial pathogens and enables clinicians and microbiologists to adjust their diagnostic techniques, and treatments to best fit the condition of the patients.


2010 ◽  
Vol 54 (7) ◽  
pp. 2953-2959 ◽  
Author(s):  
Emilio Pérez-Trallero ◽  
Jose E. Martín-Herrero ◽  
Ana Mazón ◽  
Celia García-Delafuente ◽  
Purificación Robles ◽  
...  

ABSTRACT A nationwide multicenter susceptibility surveillance study (Susceptibility to the Antimicrobials Used in the Community in España [SAUCE] project), SAUCE-4, including 2,559 Streptococcus pneumoniae, 2,287 Streptococcus pyogenes, and 2,736 Haemophilus influenzae isolates was carried out from May 2006 to June 2007 in 34 Spanish hospitals. Then, the results from SAUCE-4 were compared to those from all three previous SAUCE studies carried out in 1996-1997, 1998-1999, and 2001-2002 to assess the temporal trends in resistance and the phenotypes of resistance over the 11-year period. In SAUCE-4, on the basis of the CLSI breakpoints, penicillin (parenteral, nonmeningitis breakpoint) and cefotaxime were the antimicrobials that were the most active against S. pneumoniae (99.8% and 99.6%, respectively). Only 0.9% of isolates had a penicillin MIC of ≥2 μg/ml. In S. pyogenes, nonsusceptibility to erythromycin was observed in 19.4% of isolates. Among the H. influenzae isolates, a β-lactamase-positive prevalence of 15.7% was found. A statistically significant temporal decreasing trend over the 11-year period was observed for nonsusceptibility (from 60.0% to 22.9%) and resistance (from 36.5% to 0.9%) to penicillin and for the proportion of erythromycin-resistant isolates of S. pneumoniae of the macrolide-lincosamide-streptogramin B (MLSB) phenotype (from 98.4% to 81.3%). A similar trend was observed for the prevalence of ampicillin resistance (from 37.6% to 16.1%), β-lactamase production (from 25.7% to 15.7%), and β-lactamase-negative ampicillin resistance (BLNAR) in H. influenzae (from 13.5% to 0.7%). Among erythromycin-resistant isolates of S. pyogenes, a significant increasing trend in the prevalence of MLSB was observed (from 7.0% to 35.5%). SAUCE-4 confirms a generalized decline in the resistance of the main respiratory pathogens to the antimicrobials as well as a shift in their resistance phenotypes.


2017 ◽  
Vol 11 (2) ◽  
pp. 9-16
Author(s):  
Nilufar Yeasmin Nili

The present study was done to evaluate a multiplex PCR based method for simultaneous detection of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae in CSF. A cross sectional study was carried out with 140 children (2 months to 12 years of age) with clinical suspicion of acute meningitis during July 2010 to June 2011. Three species-specific primers were used along with universal primers of bacterial gene 16S rRNA, in a two-stage PCR assay for diagnosis of acute bacterial meningitis.Among 140 patients, 42 (30%) cases were diagnosed as bacterial meningitis and other 98 (70%) as viral meningitis by clinical and cytobiochemical criteria. Out of 42 bacterial meningitis cases, 9 (21.43%) were positive by Gram stain.These 9 cases were also positive by bacterial culture and PCR. Again, 15 (35.71%) were positive by bacterial culture which were also PCR positive. In 27 cases (out of 42), the etiologic diagnosis was not possible using routine bacteriological methods; in 11 of these patients, the etiologic agents were identified by PCR. In addition, PCR recognized 5 more cases whose etiologic diagnosis was not possible, as they were identified by universal primer of 16S rRNA. Hence, among 31 (73.81%) PCR positive cases, 12 (38.71%) were S. pneumoniae, 10 (32.26%) were H. influenzae, 4 (12.9%) were N. meningitidis and 5 (16.13%) were other bacteria.Among the antibiotic users, bacterial meningitis case detection by PCR was higher (65.52%) than that of culture (10.34%) and Gram staining (6.90%). The overall sensitivity and specificity of PCR assay was 100% and 66% respectively when bacterial culture was considered as gold standard. PCR can be used as a valuable supplementary diagnostic technique in routine clinical practice for diagnosis of acute bacterial meningitis in hospital setting. Bangladesh J Med Microbiol 2017; 11 (2): 9-16


2010 ◽  
Vol 3 ◽  
pp. MBI.S3819
Author(s):  
A. Guèye Ndiaye ◽  
Hounkponou Edwige ◽  
Fatou Bintou Guèye ◽  
Cheikh Saad Bouh Boye

Development of antibiotic resistance among common respiratory pathogens is a major cause of concern worldwide. Streptococcus pneumoniae and Haemophilus influenzae are among the most common respiratory pathogens. In this study, representative samples obtained from 3 different medical centers in Dakar, Senegal were subjected to antibiotic susceptibility testing. The samples were collected from 2005 to 2008 and the data obtained was compared to establish resistance patterns between the two years (i.e. 2005–2006 to 2007–2008). S. pneumoniae exhibited a significant increase in the resistance to azithromycin and the intermediate susceptibility to penicillin G and cotrimoxazole. H. influenzae also exhibited a significant increase in resistance to azithromycin and intermediate susceptibility to chloramphenicol. None of H. influenzae samples were resistant to amoxicillin/clavulanic acid, cephalosporin and fluroquinolones and most of the S. pneumoniae isolates demonstrated high susceptibility to the antibiotics tested. Results from this study will provide greater insights to antibiotic therapy during respiratory tract infections in Dakar, Senegal. This study also establishes the importance of continuous monitoring of antibiotic susceptibility patterns that are often region-specific.


Author(s):  
Youssef Ikken ◽  
Amina Benaouda ◽  
Latifa Ibn Yaich ◽  
Farida Hilali ◽  
Yassine Sekhsokh ◽  
...  

AbstractBacteriological cultures from cerebrospinal fluids (CSF) have less sensitivity and specificity compared to quantitative PCR (RT-PCR), and multiple facts still conduct to the increase of negative culture. The aims of this study are to determine the molecular epidemiology and the simultaneous detection of bacterial meningitis in Morocco by using RT-PCR and compared this molecular approach with culture method to improve the etiological diagnosis of meningitis. The CSFs were collected over one-year period in 2018 in different hospitals covering all regions of the Kingdom of Morocco, from patients with suspected meningitis. The results showed the confirmation rate per culture recorded a rate of 33% and the RT-PCR of 70%. Molecular epidemiology is predominant of Neisseria meningitidis followed by Streptococcus pneumoniae and a dramatic reduction in meningitis due to Haemophilus influenzae following the introduction of conjugate vaccine in 2007. Also, the epidemiological profile shows a sex ratio M/F of 1.4 and a median age of 2 years. The national distribution showed a predominant of meningococcal disease followed by pneumococcal disease, especially a dominance of N. meningitidis over S. pneumoniae in two regions and a slight predominance of S. pneumoniae in the other two regions over N. meningitidis. Our research shows that culture in our country has less sensitivity and specificity than RT-PCR in diagnosis of bacterial meningitis and that molecular biology technique at bacteriology laboratories is desirable for diagnosis, early management of meningitis cases and in the context of the surveillance of meningitis in Morocco in parallel with culture.


2005 ◽  
Vol 49 (4) ◽  
pp. 1633-1635 ◽  
Author(s):  
Elizabeth D. Hermsen ◽  
Laurie B. Hovde ◽  
George N. Konstantinides ◽  
John C. Rotschafer

ABSTRACT The purpose of this study was to compare the mutant prevention concentration (MPC) of ABT-492 to those of levofloxacin, moxifloxacin, and gatifloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The fluoroquinolones had comparable mutation selection windows, which is the ratio of MPC/MIC, for all isolates.


Author(s):  
Kokori Bajeh Tijani ◽  
Abdullahi Attah Alfa ◽  
Abdullahi Aminu Sezor

The studies on phytochemical, nutraceutical profiles and potential medicinal values of Allium sativum linn (lilliaceae) on bacterial meningitis were evaluated against bacterial meningitis pathogens. The methods employed in this study were validation of phytochemical screening which was done according to standard methods, determination of nutritional composition was carried out using analytical automated instruments (Atomic Absorption Spectrometers) and evaluation of in vitro antibacterial activities of the extracts against clinical isolates using agar-well diffusion and broth dilution methods. The clinical isolates of meningitis pathogens, Streptococcus pneumoniae, Neisseria meningitides, Klebsiella pneumoniae, Haemophilus influenzae and Escherichia coli were obtained from Ahmadu Bello University Teaching Hospital (ABUTH), Shika-Zaria. The collected bulbs of A. sativum (600 g) were washed and air dried under shade for 2 hours and the dry scaly outer covering was peeled-off to obtain the fresh garlic cloves which were then divided into three parts of 200 g each. These three portions were crushed separately for cold extraction. The first portion was homogenized and poured into a muslin cloth to squeeze out the juice, while second and third portions were homogenized and submerged into 500 ml of 96% ethanol and 500 ml of distilled water respectively for 24 hours and both filtered after thorough shaking. The first and second portions were freeze dried, while the third portion was evaporated over water bath at 50°C to obtain the powdered yield. The phytochemical screening of A. sativum extracts (JEAS, EEAS and AEAS) revealed the presence of alkaloids, carbohydrates, cardiac glycosides, fats & oils, flavonoids, saponins and steroidal terpenoids. The results obtained as nutritional profiles from analytical automated machines analysis showed that A. sativum contained all classes of food nutrients such as carbohydrate, protein, fat and oils, dietary fibres, and vitamins together with zeolite herbominerals (nanopharmacologic effects). JEAS and EEAS extracts were potent in (0.94 ± 0.01 minutes), (0.99±0.04) and antibacterial activities while and AEAS (1.20±0.04) showed low activity, inhibiting the clinical bacterial isolates Neisseria meningitides, Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli with diameter of zone of inhibition ranging from 15-36 mm at concentrations of 10, 15, 20 and 25 mg/ml. It produced significant (p<0.05) antibacterial activity while EEAS and AEAS showed low activities, except Klebsiella pneumoniae which was resistant to the three extracts concentrations used. The extracts inhibited the growth of the bacterial isolates in a concentration dependent manner with MICs ranging between 0.04-1.56 mg/ml while MBCs was 0.10-2.50 mg/ml respectively the findings from this study could be of interest and suggest the need for further investigations with a view to use the plant in novel drug development for BM therapy. The outcome of this study could therefore justify the ethnomedical and folkloric usage of A. sativum to treat bacterial meningitis locally.


Sign in / Sign up

Export Citation Format

Share Document