scholarly journals A New Phage Lysin Isolated from the Oral Microbiome Targeting Streptococcus pneumoniae

2020 ◽  
Vol 13 (12) ◽  
pp. 478
Author(s):  
Imme van der Kamp ◽  
Lorraine A. Draper ◽  
Muireann K. Smith ◽  
Colin Buttimer ◽  
R. Paul Ross ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Multidrug Resistant ◽  
Oral Microbiome ◽  
Lytic Activity ◽  
Host Strain ◽  
Pneumococcal Infections ◽  
Highly Pathogenic ◽  
Cell Counts ◽  
Colony Forming Units ◽  
Invasive Infections

Streptococcus pneumoniae is highly pathogenic and causes several mucosal and invasive infections. Due to the rising number of multidrug-resistant (MDR) strains of S. pneumoniae, new antimicrobials with alternative mechanisms of action are urgently needed. In this study, we identified two new Streptococcal phages from the oral microbiome, 23TH and SA01. Their lysins, 23TH_48 and SA01_53, were recombinantly expressed, characterized and tested for their lethality. SA01_53 was found to only lyse its host strain of S. anginosus, while 23TH_48 was found to possess a broader lytic activity beyond its host strain of S. infantis, with several S. pneumoniae isolates sensitive to its lytic activity. 23TH_48 at a concentration of five activity units per mL (U/mL) was found to reduce cell counts of S. pneumoniae DSM 24048 by 4 log10 colony forming units per mL (CFU/mL) within 1 h and effectively prevented and destroyed biofilms of S. pneumoniae R6 at concentrations of 228.8 ng/µL and 14.3 ng/µL, respectively. Given its high lytic activity, 23TH_48 could prove to be a promising candidate to help combat pneumococcal infections.

scholarly journals Prevalence and Antimicrobial Susceptibility of Streptococcus pneumoniae Isolated from Clinical Samples in the Past 8 Years in Korea

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jae Soo Kim ◽  
Bo Kyeung Jung ◽  
Jong Wan Kim ◽  
Ga Yeon Kim
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Pneumococcal Infection ◽  
Multidrug Resistant ◽  
Clinical Samples ◽  
Resistant Bacteria ◽  
Microbial Culture ◽  
Pneumococcal Infections ◽  
The Past ◽  
Invasive Infections

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.

Invasive Streptococcus Pneumoniae Infections in Pediatric Cancer Patients: High Morbidity and Mortality with Several Vaccine Failures.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3321-3321
Author(s):  
Lynn Weber ◽  
Charlet A. Allen ◽  
Patricia Ackerman ◽  
Yoav Messinger
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pediatric Oncology ◽  
Pneumococcal Infection ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Invasive Infection ◽  
Pneumococcal Infections ◽  
Oncology Patients ◽  
Invasive Infections ◽  
Invasive Pneumococcal Infection

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.

scholarly journals Implications of Streptococcus pneumoniae Penicillin Resistance and Serotype Distribution in Kuwait for Disease Treatment and Prevention

2007 ◽  
Vol 15 (2) ◽  
pp. 203-207 ◽  
Author(s):  
Eiman M. Mokaddas ◽  
Vincent O. Rotimi ◽  
M. John Albert
Keyword(s):  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Arabian Gulf ◽  
Age Groups ◽  
Penicillin Resistance ◽  
Background Information ◽  
Upper Respiratory Tract ◽  
Pneumococcal Infections ◽  
Invasive Infections ◽  
Common Serotypes

ABSTRACT Streptococcus pneumoniae causes serious infections. Treatment is difficult because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal vaccines offer the promise of control and prevention of pneumococcal infections. Serotype prevalence and penicillin susceptibility data for a country will predict the usefulness of the vaccines in that country. In Kuwait, the 23-valent polysaccharide and the 7-valent conjugate vaccines are being used without knowledge of the prevalent serotypes in the country. To obtain the necessary background information, data on penicillin susceptibility and serogroups were obtained from 397 consecutive clinical isolates collected during 2004 and 2005. Two hundred fifty-three isolates (64%) were penicillin resistant, and resistance was significantly higher in patients ≤15 years old and among the upper respiratory tract and eye isolates. The most common serotypes were 23F, 19F, 6A, 6B, 14, and 19A. Among the penicillin-resistant strains, the most common serotypes were 23F, 19F, 6B, 14, and 9A. Among the invasive strains, the most common serotypes were 14, 23F, 19A, and 9V. The polysaccharide vaccine gave 82% coverage against invasive infections in all age groups >2 years. The coverage of the 7-valent conjugate vaccine against invasive serotypes in children ≤2 years old was 55%. This moderate coverage by the conjugate vaccine against invasive infections in children necessitates a revised strategy on the use of the present conjugate vaccine and shows the need for formulation of an improved vaccine for superior coverage for Kuwait and possibly other countries of the Arabian Gulf.

scholarly journals Trends in Antimicrobial Drug Resistance of Streptococcus pneumoniae Isolates at Jordan University Hospital (2000–2018)

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 41 ◽  
Author(s):  
Malik Sallam
Keyword(s):  
Drug Resistance ◽  
Streptococcus Pneumoniae ◽  
Trend Analysis ◽  
Empiric Therapy ◽  
Antimicrobial Drug ◽  
University Hospital ◽  
Multi Drug Resistance ◽  
Pneumococcal Infections ◽  
Antimicrobial Drug Resistance ◽  
Invasive Infections

Antimicrobial drug resistance (AMR) in pneumococci complicates the treatment of serious pneumococcal infections. Country-specific AMR patterns can help to establish guidelines for empiric therapy. The aim of the current study was to analyze the distribution of AMR among Streptococcus pneumoniae isolates at Jordan University Hospital (JUH) during 2000–2018. Paper-based and electronic clinical data registry records from 2000 to 2018 were retrospectively analyzed to study the AMR among pneumococcal isolates at JUH. Temporal trend analysis was done using two-tailed linear-by-linear test for association. The total number of unique pneumococcal isolates that were identified was 556, of which 544 isolates had antimicrobial susceptibility testing results. The most frequent specimens were eye (n = 117, 21.0%), bloodstream (n = 93, 16.7%) and sputum (n = 81, 14.6%). Invasive infections represented 23.6% of all unique isolates. The overall susceptibility of S. pneumoniae isolates during the study period to different antimicrobials was: 100% to vancomycin, 97.7% to ceftriaxone, 97.1% to cefotaxime, 94.9% to chloramphenicol, 89.7% to penicillin, 83.8% to levofloxacin, 67.7% to clindamycin and 52.1% to erythromycin. The prevalence of multi-drug resistance (MDR) was 8.6% (95% confidence interval: 6.4–11.5%). Trend analysis showed an increase in the prevalence of non-susceptibility to erythromycin, clindamycin and levofloxacin (p < 0.001). MDR prevalence increased from 1.6% in the first quarter to 14.6% in the fourth quarter (p < 0.001). The incidence of invasive infections declined over the study period (p < 0.001). The increase in the prevalence of AMR and MDR among pneumococcal isolates in Jordan demands judicious use of antimicrobials and regular surveillance of resistance.

scholarly journals Draft Genome Sequences of Two Streptococcus pneumoniae Strains Causing Invasive Infections in Children in Qatar

2019 ◽  
Vol 8 (23) ◽  
Author(s):  
Clement K. M. Tsui ◽  
Sathyavathi Sundararaju ◽  
Hassan Al Mana ◽  
Eva Thomas ◽  
Patrick Tang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pediatric Population ◽  
Draft Genome ◽  
Morbidity And Mortality ◽  
Pneumococcal Infections ◽  
Genome Sequences ◽  
Content Type ◽  
Invasive Infections ◽  
Severe Infections

Invasive pneumococcal infections are a major cause of morbidity and mortality in the pediatric population. We report the draft genomes of two clinical Streptococcus pneumoniae isolates associated with severe infections in children in Qatar.

scholarly journals An Assessment of the Viability of Lytic Phages and Their Potency against Multidrug Resistant Escherichia coli O177 Strains under Simulated Rumen Fermentation Conditions

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 265
Author(s):  
Peter Kotsoana Montso ◽  
Caven Mguvane Mnisi ◽  
Collins Njie Ateba ◽  
Victor Mlambo
Keyword(s):  
Escherichia Coli ◽  
Rumen Fluid ◽  
Multidrug Resistant ◽  
Rumen Fermentation ◽  
Ruminal Fermentation ◽  
Fermentation Conditions ◽  
E Coli ◽  
Cell Counts ◽  
Milk Contamination ◽  
Novel Strategy

Preslaughter starvation and subacute ruminal acidosis in cattle are known to promote ruminal proliferation of atypical enteropathogenic Escherichia coli strains, thereby increasing the risk of meat and milk contamination. Using bacteriophages (henceforth called phages) to control these strains in the rumen is a potentially novel strategy. Therefore, this study evaluated the viability of phages and their efficacy in reducing E. coli O177 cells in a simulated ruminal fermentation system. Fourteen phage treatments were allocated to anaerobic serum bottles containing a grass hay substrate, buffered (pH 6.6–6.8) bovine rumen fluid, and E. coli O177 cells. The serum bottles were then incubated at 39 °C for 48 h. Phage titres quadratically increased with incubation time. Phage-induced reduction of E. coli O177 cell counts reached maximum values of 61.02–62.74% and 62.35–66.92% for single phages and phage cocktails, respectively. The highest E. coli O177 cell count reduction occurred in samples treated with vB_EcoM_366B (62.31%), vB_EcoM_3A1 (62.74%), vB_EcoMC3 (66.67%), vB_EcoMC4 (66.92%), and vB_EcoMC6 (66.42%) phages. In conclusion, lytic phages effectively reduced E. coli O177 cells under artificial rumen fermentation conditions, thus could be used as a biocontrol strategy in live cattle to reduce meat and milk contamination in abattoirs and milking parlours, respectively.

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 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.

scholarly journals Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

2001 ◽  
Vol 45 (4) ◽  
pp. 1037-1042 ◽  
Author(s):  
Daniel F. Sahm ◽  
James A. Karlowsky ◽  
Laurie J. Kelly ◽  
Ian A. Critchley ◽  
Mark E. Jones ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
The United States ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Resistance Patterns ◽  
Changing Patterns ◽  
Resistance To Penicillin

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

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