Immunity to Sda1 Protects against Infection by Sda1+ and Sda1− Serotypes of Group A Streptococcus

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases.

The salivary, metal-binding peptide histatin-5 buffers extracellular copper availability

The family of human salivary histidine-rich peptides known as histatins bind zinc (Zn) and copper (Cu), but whether they contribute to nutritional immunity by influencing Zn and/or Cu availability has not been examined. We hypothesised that histatin-5 (Hst5) limits Zn availability (and promotes bacterial Zn starvation) and/or raises Cu availability (and promotes bacterial Cu poisoning). To test this hypothesis, Group A Streptococcus (GAS), which colonises the human oropharynx, was used as a model bacterium. Contrary to our hypothesis, Hst5 did not strongly influence Zn availability. This peptide did not induce expression of Zn uptake genes in GAS, nor did it suppress growth of an ΔadcAI mutant strain that is impaired in Zn uptake. Equilibrium competition measurements confirmed that Hst5 binds Zn weakly and does not compete with the high-affinity Zn uptake protein AdcAI for binding Zn. By contrast, Hst5 bound Cu with a high affinity and strongly influenced Cu availability. However, contrary to our hypothesis, Hst5 did not promote Cu toxicity. Instead, this peptide suppressed expression of Cu-inducible genes in GAS, stopped intracellular accumulation of Cu, and rescued growth of a ΔcopA mutant strain that is impaired in Cu efflux in the presence of added Cu. These findings led us to propose a new role for Hst5 and salivary histatins as major Cu buffers in saliva that reduce the potential negative effects of Cu exposure to microbes. We speculate that histatins promote oral and oropharyngeal health by contributing to microbial homeostasis in these host niches.

Use of the McIsaac Score to Predict Group A Streptococcal Pharyngitis in Outpatient Nurse Phone Triage and Electronic Visits Compared With In-Person Visits: Retrospective Observational Study

Background The McIsaac criteria are a validated scoring system used to determine the likelihood of an acute sore throat being caused by group A streptococcus (GAS) to stratify patients who need strep testing. Objective We aim to compare McIsaac criteria obtained during face-to-face (f2f) and non-f2f encounters. Methods This retrospective study compared the percentage of positive GAS tests by McIsaac score for scores calculated during nurse protocol phone encounters, e-visits (electronic visits), and in person f2f clinic visits. Results There was no difference in percentages of positive strep tests between encounter types for any of the McIsaac scores. There were significantly more phone and e-visit encounters with any missing score components compared with f2f visits. For individual score components, there were significantly fewer e-visits missing fever and cough information compared with phone encounters and f2f encounters. F2f encounters were significantly less likely to be missing descriptions of tonsils and lymphadenopathy compared with phone and e-visit encounters. McIsaac scores of 4 had positive GAS rates of 55% to 68% across encounter types. There were 4 encounters not missing any score components with a McIsaac score of 0. None of these 4 encounters had a positive GAS test. Conclusions McIsaac scores of 4 collected during non-f2f care could be used to consider empiric treatment for GAS without testing if significant barriers to testing exist such as the COVID-19 pandemic or geographic barriers. Future studies should evaluate further whether non-f2f encounters with McIsaac scores of 0 can be safely excluded from GAS testing.

Prevalence and antibiotic susceptibility of Streptococcus pyogenes isolated from pyoderma in a tertiary care hospital, Hyderabad, South India

Pyoderma is a common acute superficial bacterial skin infection which is highly contagious. In the great majority of cases, pyoderma is caused by , , or both. The present study was carried out to determine the prevalence and antibiotic susceptibility of isolated from pyoderma in Dr. VRK Women’s Teaching hospital. Swabs or pus samples were collected from 250 patients attending Dermatology, outpatient department (OPD) of Dr. VRK Women’s Teaching hospital. Samples were inoculated onto 5% sheep blood agar plates and incubated for 24 h at 37°C in a candle jar. BHS isolates were phenotypically identified by standard microbiological techniques, all the isolates presumptively identified as BHS were tested for Bacitracin susceptibility. Presumptive identification of a strain as a Group A Streptococcus (GAS) was also made by PYRase test. Presumptively identified GAS isolates were serogrouped by Lancefield grouping using a commercially available latex agglutination test. isolates were subjected to antimicrobial susceptibility testing by Kirby-Bauer disc diffusion method. BHS were isolated from 30% of samples. Prevalence of BHS was more among 0-10 years age group (38%). BHS were isolated more frequently from males (38.8%). were isolated from 52 (20.8%) samples. All 52 isolates were found to be susceptible to Penicillin G, amoxicillin, ceftriaxone, azithromycin and vancomycin. Erythromycin and clindamycin showed good activity with sensitivity rates of 92.3% & 96.1%, respectively. Resistance to tetracycline (59.6%) and chloramphenicol (23.1%) was commonly seen in . This study reports the prevalence and antibiotic susceptibility of isolated from pyoderma in Dr. VRK Women’s Teaching hospital. Results of this study suggests the peak incidence of pyoderma in children aged 0 to 10 years and male preponderance. Our study also reports high prevalence of tetracycline and chloramphenicol resistance in .

Overview on Acute Poststreptococcal Glomerulonephritis in Pediatrics: A Review

Acute poststreptococcal glomerulonephritis (APSGN) is the most common kind of post-infectious glomerulonephritis and is caused by group A streptococcus (Streptococcus pyogenes). Although the prevalence of PSGN has decreased in affluent nations, non-streptococcal species are becoming more common. and it is still the major cause of glomerulonephritis in children. APSGN can manifest itself in epidemic outbreaks or clusters of instances, as well as in single persons. Epidemic outbreaks have previously been documented as a result of upper respiratory or cutaneous streptococcal infections in various parts of the world. In developed nations, APSGN is now mostly a disease of the elderly, who are more likely to have disabling illnesses such as cancer, alcoholism, or diabetes. Children between the ages of 3 and 12 (with a peak incidence between the ages of 5 and 6 years) and seniors over the age of 60 are the most commonly affected. The pathophysiology of APSGN is complicated by inflammation. (APSGN) often occurs one to two weeks after a throat infection and three to five weeks after a skin infection. Hematuria, edoema, azotemia, and hypertension are the most common clinical signs. Loop or thiazide diuretics, are the most effective therapy for hypertension and edoema in PSGN. In this review we’ll be looking at the disease causes, epidemiology, presentation and treatment.

Synergistic collagen-condiment: Streptococcal collagen-like (Scl) protein in cell-adhesion and diabetic wound-closure matrix

Group A streptococcus (GAS), Streptococcus pyogenes manifests plethora of diseases through its explicit virulence factors. Among these, the recently deciphered MSCRAMMs, Streptococcal collagen-like (Scls) adhesins are most studied proteins in context of their biophysically stable collagenous-sequence (Gly-X-Y) despite the difference from analogous mammalian-collagen. Based on recent evidence on collagen-mimetic Scls, we elucidated biomaterial-potential of the unmodified, recombinant Scl1 (rScl1). Initially, rScl1 trimeric- assembly yielded its stability in silico than the monomeric-unit. Thereby, rScl1 matrix characterization was confirmed in vitro. rScl1 exhibited high A549 and HepG2 cell- viability—rScl1 dose incremented to 20.0 µg/ml at time points up to 24 hr, and on 24 hr stored-dishes—deliberating it non-cytotoxic. Imploring cell-adhesion potential, we observed increased cell-counts tangential to rScl1-gradient. This affirmative prelude on rScl1 as a supporting-matrix cued its synergy to collagen; we discerned it through rScl1-augmented, full-thickness diabetic wound-closure in vivo and as a first, we studied > 18-month rabbit alloxan-models. We have ascertained re-epithelialization with higher type III collagen in absence of inflammation evidenced morphometrically and histologically. Finally, we correlated our observations through atomistic-evaluation of rScl1-α2β1-integrin interaction, surprisingly, with augmented binding-energy compared to collagen. Hence, connoting recombinant-streptococcal collagen as an ‘alternate’; with further characterization, rScl1 can potentiate important revelations conceding homogeneous and safe, bio-available, biomaterial.

Life-threatening complications of streptococcal sepsis: a PICU contemporary series

Background Life-threatening streptococcal sepsis nowadays represents an uncommon event in previously healthy infants and children. Critically ill patients suffering from severe streptococcal sepsis complications may present with pre-antibiotic era clinical pictures and require a timely clinical approach to achieve restitutio ad integrum. Results We report a series of four patient groups affected by an uncommon life-threatening streptococcal sepsis, each of them exhibiting some distinct features. Streptococcus Agalactiae sepsis was associated with cerebral thrombotic/ischaemic lesions, whereas severe cardiogenic shock was prominent in the Streptococcus Viridans group; Streptococcus Faecalis and β-hemolytic group A Streptococcus patients mostly reported lung complications. Conclusions Previous antibiotic treatments should not delay aggressive treatment in the intensive care setting. Early diagnostic suspicion, as well as appropriate and aggressive treatment provided within an intensive care setting are crucial for the clinical outcome.

Preceding group A streptococcus skin and throat infections are individually associated with acute rheumatic fever: evidence from New Zealand

IntroductionAcute rheumatic fever (ARF) is usually considered a consequence of group A streptococcus (GAS) pharyngitis, with GAS skin infections not considered a major trigger. The aim was to quantify the risk of ARF following a GAS-positive skin or throat swab.MethodsThis retrospective analysis used pre-existing administrative data. Throat and skin swab data (1 866 981 swabs) from the Auckland region, New Zealand and antibiotic dispensing data were used (2010–2017). Incident ARF cases were identified using hospitalisation data (2010–2018). The risk ratio (RR) of ARF following swab collection was estimated across selected features and timeframes. Antibiotic dispensing data were linked to investigate whether this altered ARF risk following GAS detection.ResultsARF risk increased following GAS detection in a throat or skin swab. Māori and Pacific Peoples had the highest ARF risk 8–90 days following a GAS-positive throat or skin swab, compared with a GAS-negative swab. During this period, the RR for Māori and Pacific Peoples following a GAS-positive throat swab was 4.8 (95% CI 3.6 to 6.4) and following a GAS-positive skin swab, the RR was 5.1 (95% CI 1.8 to 15.0). Antibiotic dispensing was not associated with a reduction in ARF risk following GAS detection in a throat swab (antibiotics not dispensed (RR: 4.1, 95% CI 2.7 to 6.2), antibiotics dispensed (RR: 4.3, 95% CI 2.5 to 7.4) or in a skin swab (antibiotics not dispensed (RR: 3.5, 95% CI 0.9 to 13.9), antibiotics dispensed (RR: 2.0, 95% CI 0.3 to 12.1).ConclusionsA GAS-positive throat or skin swab is strongly associated with subsequent ARF, particularly for Māori and Pacific Peoples. This study provides the first population-level evidence that GAS skin infection can trigger ARF.

Incidence and mortality of necrotizing fasciitis in The Netherlands: the impact of group A Streptococcus

Background Little is known about the exact incidence of necrotizing soft tissue infections. The few incidences reported in international literature are not directly relatable to the Netherlands, or other European countries, due to geographic heterogeneity in causative micro-organisms involved. This resulted in the aim of this study to map the incidence, mortality rate and hospital course of necrotizing fasciitis infections in the Netherlands to gain insight in the incidence of necrotizing fasciitis in the Netherlands and the associated mortality and health care burden. Methods This nationwide retrospective database study used three distinct data sources to map the incidence of necrotizing fasciitis in the Netherlands between 2014 and 2019, being data from the Dutch Hospital Data (DHD) foundation, data from Osiris-AIZ, which is a database of notifiable diseases managed by regional Public Health Services (GGD) and the National Institute for Public Health and the Environment (RIVM), and previously published studies on necrotizing fasciitis conducted in the Netherlands. Results The incidence of necrotizing fasciitis in the Netherlands is estimated to be approximately 1.1 to 1.4 cases per 100,000 person years, which corresponds to 193–238 patients per year. Of all necrotizing fasciitis infections, 34 to 42% are caused by the group A Streptococcus. Annually, 56 patients die as a result of a necrotizing fasciitis infection (mortality of 23–29%) and 26 patients undergo an amputation for source control (11–14%). Patients stay a mean of 6 to 7 days at the intensive care unit and have a mean hospital length of stay of 24 to 30 days. Conclusion The combination of nationwide databases provides reliable insight in the epidemiology of low-incidence and heterogenic diseases. In the Netherlands, necrotizing fasciitis is a rare disease with group A Streptococcus being the most common causative micro-organism of necrotizing fasciitis. The prior Dutch cohort studies on necrotizing fasciitis report slightly higher sample mortality rates, compared to the population mortality. However, necrotizing fasciitis remain associated with substantial morbidity and mortality, risk at amputation and health care burden characterized by prolonged ICU and hospital stay.