Publications by authors named "Sriskandan S"

is a Gram-negative nosocomial pathogen of the ESKAPE (, and spp.) priority group with increasing multi-drug resistance via the acquisition of resistance plasmids. However, can also display forms of antibiotic refractoriness, such as heteroresistance and tolerance.

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A woman in her 40s known to have systemic lupus erythematosus presented with a maculopapular rash on her face, neck and chest following measles exposure. She had received a single-dose measles vaccine as a child in the 1970s and was therefore presumed to be immune, and thus not infectious. As a result, she was initially managed in an open bay.

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Article Synopsis
  • * Lineage M1 has emerged as the primary cause of these invasive infections, showing reduced genetic diversity and fewer mutations compared to earlier M1 strains that date back to 2008.
  • * Despite being undetected before, M1 clades rapidly spread across the UK after the COVID-19 pandemic, suggesting that waning immunity and specific genetic traits enhance their ability to cause epidemics and survive population bottlenecks.
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Group A streptococcus (GAS) infections result in more than 500 000 deaths annually. Despite mounting evidence for airborne transmission of GAS, little is known about its stability in aerosol. Measurements of GAS airborne stability were carried out using the Controlled Electrodynamic Levitation and Extraction of Bioaerosols onto a Substrate (CELEBS) instrument.

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  • * In a study analyzing RNAseq data from different strains, deletion of RofA in M1 strains affected expression levels of several genes, with distinct impacts on each lineage regarding non-pilus genes.
  • * Changes in gene expression due to specific SNPs in the M1 lineage didn't significantly affect an M1 strain, but reversing those SNPs resulted in notable transcriptomic changes similar to those caused by RofA deletion, indicating a complex regulatory role that requires further exploration.
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The Streptococcus pyogenes cell envelope protease (SpyCEP) is vital to streptococcal pathogenesis and disease progression. Despite its strong association with invasive disease, little is known about enzymatic function beyond the ELR CXC chemokine substrate range. As a serine protease, SpyCEP has a catalytic triad consisting of aspartate (D151), histidine (H279), and serine (S617) residues which are all thought to be mandatory for full activity.

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Awareness of neurological sequelae of dengue fever is increasing. However, as this case illustrates, there is a diagnostic conundrum in determining whether certain features are in keeping with dengue encephalopathy or dengue encephalitis. Further consensus is required.

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Nitrofurantoin is a broad-spectrum first-line antimicrobial used for managing uncomplicated urinary tract infection (UTI). Loss-of-function mutations in chromosomal genes and of are known to reduce nitrofurantoin susceptibility. Here, we report the discovery of nitrofurantoin heteroresistance in clinical isolates and a novel genetic mechanism associated with this phenomenon.

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Annually, over 18 million disease cases and half a million deaths worldwide are estimated to be caused by Group A Streptococcus. ScpA (or C5a peptidase) is a well characterised member of the cell enveleope protease family, which possess a S8 subtilisin-like catalytic domain and a shared multi-domain architecture. ScpA cleaves complement factors C5a and C3a, impairing the function of these critical anaphylatoxins and disrupts complement-mediated innate immunity.

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Article Synopsis
  • Streptococcus pyogenes (Strep A) infections are a significant global health issue, often overlooked, leading to both acute and chronic diseases.* -
  • The Strep A Vaccine Global Consortium (SAVAC) aims to fast-track the development of safe and effective vaccines for Strep A, prioritizing the safety of recipients.* -
  • Though no safety concerns were noted in recent early-phase clinical trials, there is a need for enhanced safety assessments specifically for pediatric trials, large efficacy studies, and ongoing monitoring after vaccines are released.*
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  • Genotype 1, particularly the M1 sublineage, is a virulent strain linked to scarlet fever outbreaks in England during 2015/2016, marked by 27 specific SNPs in its genome.
  • Comparative analyses revealed only seven differentially expressed genes in M1 compared to other strains, with key metabolic changes influencing pathogen behavior.
  • The evolution of M1 is attributed to a stepwise accumulation of SNPs that enhance its fitness, allowing it to outcompete other related strains, despite having similar toxin production capabilities.
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  • * Out of over 5,000 records, 43 studies were analyzed, showing that the rates of GAS positivity were 6.9% on day 1, 5.4% on day 2, and 2.6% on days 3-9 after starting treatment with antibiotics.
  • * While the findings suggest antibiotics effectively reduce GAS positivity in 24 hours, the authors emphasized the need for more rigorous research to address current study limitations and to evaluate the effectiveness of non-beta-lactam antibiotics and cases in asymptomatic individuals.
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Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1. An allele-specific PCR was developed to distinguish M1 from other emm1 strains. The M1 lineage represented 91% of invasive emm1 isolates in England in 2020.

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Understanding immunity in humans to Group A Streptococcus (Strep A) is critical for the development of successful vaccines to prevent the morbidity and mortality attributed to Strep A infections. Despite decades of effort, no licensed vaccine against Strep A exists and immune correlates of protection are lacking; a major impediment to vaccine development. In the absence of a vaccine, we can take cues from the development of natural immunity to Strep A in humans to identify immune correlates of protection.

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Background: Surfaces and air in healthcare facilities can be contaminated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Previously, the authors identified SARS-CoV-2 RNA on surfaces and air in their hospital during the first wave of the coronavirus disease 2019 pandemic (April 2020).

Aim: To explore whether the profile of SARS-CoV-2 surface and air contamination had changed between April 2020 and January 2021.

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The incidence of necrotising soft-tissue infections has increased during recent decades such that most physicians might see at least one case of these potentially life-threatening infections in their career. Despite advances in care, necrotising soft-tissue infections are still associated with high morbidity and mortality, underlining a need for continued education of the medical community. In particular, failure to suspect necrotising soft-tissue infections, fuelled by poor awareness of the disease, promotes delays to first surgical debridement, amplifying disease severity and adverse outcomes.

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Background: Assessing transmission of SARS-CoV-2 by children in schools is of crucial importance to inform public health action. We assessed frequency of acquisition of SARS-CoV-2 by contacts of pupils with COVID-19 in schools and households, and quantified SARS-CoV-2 shedding into air and onto fomites in both settings.

Methods: We did a prospective cohort and environmental sampling study in London, UK in eight schools.

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The 16S rRNA methyltransferase (16S RMTase) gene is the most common mechanism conferring high-level aminoglycoside resistance in , although , , , and have also been reported. The occurrence of 16S RMTase genes in in the UK and Republic of Ireland is currently unknown. To identify the occurrence of 16S RMTase genes in isolates from the UK and the Republic of Ireland between 2004 and 2015.

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Background: Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014 and 2018. We aimed to assess the effects of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments to inform future guidance.

Methods: We did a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in six settings across five schools in Greater London, UK.

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Objectives: Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of MDR lineages such as ST131 to overall E. coli disease burden and outcome is undetermined.

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16S rRNA methyltransferase (16S RMTase) genes confer high-level aminoglycoside resistance, reducing treatment options for multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa isolates (n = 221) exhibiting high-level pan-aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) were screened for 16S RMTase genes to determine their occurrence among isolates submitted to a national reference laboratory from December 2003 to December 2015. 16S RMTase genes were identified using two multiplex PCRs, and whole-genome sequencing (WGS) was used to identify other antibiotic resistance genes, sequence types (STs) and the genetic environment of 16S RMTase genes.

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Background: There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing.

Methods: Using untargeted high-resolution liquid chromatography coupled with mass spectrometry, we compared the admission serum metabolome of emergency department patients with viral infections (including COVID-19), bacterial infections, inflammatory conditions, and healthy controls. Sera from an independent cohort of emergency department patients admitted with viral or bacterial infections underwent profiling to validate findings.

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Lymphatic vessels permeate tissues around the body, returning fluid from interstitial spaces back to the blood after passage through the lymph nodes, which are important sites for adaptive responses to all types of pathogens. Involvement of the lymphatics in the pathogenesis of bacterial infections is not well studied. Despite offering an obvious conduit for pathogen spread, the lymphatic system has long been regarded to bar the onward progression of most bacteria.

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