Genomic cluster formation among invasive group A streptococcal infections in the USA: a whole-genome sequencing and population-based surveillance study.

Background: Clusters of invasive group A streptococcal (iGAS) infection, linked to genomically closely related group A streptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters.

Methods: In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention's Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019.

A novel invasive Streptococcus pyogenes variant sublineage derived through recombinational replacement of the emm12 genomic region.

Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12.

Variation in pneumococcal invasiveness metrics is driven by serotype carriage duration and initial risk of disease.

Streptococcus pneumoniae is an opportunistic pathogen that, while usually carried asymptomatically, can cause severe invasive diseases like meningitis and bacteremic pneumonia. A central goal in S. pneumoniae public health management is to identify which serotypes (immunologically distinct strains) pose the most risk of invasive disease.

Expansion of Invasive Group A Streptococcus M1 Lineage in Active Bacterial Core Surveillance, United States, 2019‒2021.

From 2015-2018 to 2019‒2021, hypertoxigenic M1 lineage among invasive group A Streptococcus increased in the United States (1.7%, 21/1,230 to 11%, 65/603; p<0.001).

Benchmark datasets for SARS-CoV-2 surveillance bioinformatics.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread globally and is being surveilled with an international genome sequencing effort. Surveillance consists of sample acquisition, library preparation, and whole genome sequencing. This has necessitated a classification scheme detailing Variants of Concern (VOC) and Variants of Interest (VOI), and the rapid expansion of bioinformatics tools for sequence analysis.

Continued Increase of Erythromycin Nonsusceptibility and Clindamycin Nonsusceptibility Among Invasive Group A Streptococci Driven by Genomic Clusters, United States, 2018-2019.

We analyzed 9630 invasive GAS surveillance isolates in the USA. From 2015-2017 to 2018-2019, significant increases in erythromycin-nonsusceptibility (18% vs 25%) and clindamycin-nonsusceptibility (17% vs 24%) occurred, driven by rapid expansions of genomic subclones. Prevention and control of clustered infections appear key to containing antimicrobial resistance.

Invasive Pneumococcal Disease Clusters Disproportionally Impact Persons Experiencing Homelessness, Injecting Drug Users, and the Western United States.

Background: Invasive pneumococcal disease (IPD) isolates forming genomic clusters can reflect rapid disease transmission between vulnerable individuals.

Methods: We performed whole genome sequencing of 2820 IPD isolates recovered during 2019 through Centers for Disease Control and Prevention's Active Bacterial Core surveillance to provide strain information (serotypes, resistance, genotypes), and 2778 of these genomes were analyzed to detect highly related genomic clusters.

Results: Isolates from persons experiencing homelessness (PEH) were more often within genomic clusters than those from persons not experiencing homelessness (PNEH) (105/198 [53.

Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016- April 2017.

Background: The genomic features and transmission link of circulating Group A Streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood.

Methods: We used whole-genome sequencing to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017.

Results: The GAS isolates were cultured from 236 invasive and 417 pharyngitis infections.

Low but Increasing Prevalence of Reduced Beta-lactam Susceptibility Among Invasive Group B Streptococcal Isolates, US Population-Based Surveillance, 1998-2018.

Background: Invasive group B (iGBS) isolates with mutations in the gene that encodes penicillin binding protein 2x can have reduced beta-lactam susceptibility (RBLS) when susceptible by Clinical and Laboratory Standards Institute (CLSI) criteria. We assessed the emergence and characteristics of RBLS strains in US iGBS isolates.

Methods: We analyzed iGBS isolates from 8 multistate population-based surveillance sites from 1998 to 2018.

Invasive Pneumococcal Strain Distributions and Isolate Clusters Associated With Persons Experiencing Homelessness During 2018.

Background: We aimed to characterize invasive pneumococcal disease (IPD) isolates collected from multistate surveillance in the United States during 2018 and examine within-serotype propensities of isolates to form related clusters.

Methods: We predicted strain features using whole genome sequencing obtained from 2885 IPD isolates obtained through the Center for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), which has a surveillance population of approximately 34.5 million individuals distributed among 10 states.

Genomic Surveillance of Strains Causing Invasive Disease, United States, 2016-2017.

Background: is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common.

Upsurge of Conjugate Vaccine Serotype 4 Invasive Pneumococcal Disease Clusters Among Adults Experiencing Homelessness in California, Colorado, and New Mexico.

After 7-valent pneumococcal conjugate vaccine introduction in the United States in 2000, invasive pneumococcal disease (IPD) due to serotype 4 greatly decreased in children and adults. Starting in 2013, serotype 4 IPD incidence increased among adults within 3 of 10 Active Bacterial Core surveillance sites. Of 325 serotype 4 cases among adults in 2010-2018, 36% were persons experiencing homelessness (PEH); incidence of serotype 4 IPD among PEH was 100-300 times higher than in the general population within these 3 areas.

Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates.

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact.

A mosaic tetracycline resistance gene tet(S/M) detected in an MDR pneumococcal CC230 lineage that underwent capsular switching in South Africa.

Objectives: We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.

Methods: We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes.

Emergent Invasive Group A Streptococcus dysgalactiae subsp. equisimilis, United States, 2015-2018.

The term group A Streptococcus is considered synonymous for the species Streptococcus pyogenes. We describe an emergent invasive S. dysgalactiae subspecies equisimilis lineage that obtained the group A antigen through a single ancestral recombination event between a group C S.

Genome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitis.

Bacterial mutations predisposing pneumococcus to causing meningitis, a more severe form of invasive pneumococcal disease (IPD), are largely unknown. Knowledge of such mutations may improve our understanding of pathogenesis and inform preventive strategies. Here we report a pneumococcal pbp1b gene mutation (pbp1bA641C causing N214T change in PBP1b transglycosylase domain) that is associated with meningitis in an exploratory cohort of IPD patients (n = 2054, p = 6.

A Population-Based Descriptive Atlas of Invasive Pneumococcal Strains Recovered Within the U.S. During 2015-2016.

Invasive pneumococcal disease (IPD) has greatly decreased since implementation in the U.S. of the 7 valent conjugate vaccine (PCV7) in 2000 and 13 valent conjugate vaccine (PCV13) in 2010.

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection.

Validation of β-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences.

Background: Genomic sequence-based deduction of antibiotic minimum inhibitory concentration (MIC) has great potential to enhance the speed and sensitivity of antimicrobial susceptibility testing. We previously developed a penicillin-binding protein (PBP) typing system and two methods (Random Forest (RF) and Mode MIC (MM)) that accurately predicted β-lactam MICs for pneumococcal isolates carrying a characterized PBP sequence type (phenotypic β-lactam MICs known for at least one isolate of this PBP type). This study evaluates the prediction performance for previously uncharacterized (new) PBP types and the probability of encountering new PBP types, both of which impact the overall prediction accuracy.

Key features of invasive pneumococcal isolates recovered in Lima, Peru determined through whole genome sequencing.

Before PCV7 introduction, invasive pneumococcal disease (IPD) was responsible for approximately 12,000-18,000 deaths annually among children <5years in Latin America. In Peru, PCV7 was introduced in 2009. We used whole genome sequencing to deduce key features of invasive strains collected in Lima, Peru from 2006 to 2011.

Invasive Serotype 35B Pneumococci Including an Expanding Serotype Switch Lineage, United States, 2015-2016.

We used whole-genome sequencing to characterize 199 nonvaccine serotype 35B pneumococcal strains that caused invasive pneumococcal disease (IPD) in the United States during 2015-2016 and related these findings to previous serotype 35B IPD data obtained by Active Bacterial Core surveillance. Penicillin-nonsusceptible 35B IPD increased during post-pneumococcal 7-valent conjugate vaccine years (2001-2009) and increased further after implementation of pneumococcal 13-valent conjugate vaccine in 2010. This increase was caused primarily by the 35B/sequence type (ST) 558 lineage.

Distinguishability and Many-Particle Interference.

Quantum interference of two independent particles in pure quantum states is fully described by the particles' distinguishability: the closer the particles are to being identical, the higher the degree of quantum interference. When more than two particles are involved, the situation becomes more complex and interference capability extends beyond pairwise distinguishability, taking on a surprisingly rich character. Here, we study many-particle interference using three photons.

Cross-resistance to lincosamides, streptogramins A and pleuromutilins in Streptococcus agalactiae isolates from the USA.

Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of meningitis, sepsis and pneumonia in neonates in the United States. GBS also causes invasive disease in older infants, pregnant women, children and young adults with underlying medical conditions, and older adults. Resistance to lincosamides in the absence of erythromycin resistance is rare in GBS, but has been previously reported in clinical isolates, both on its own or in combination with resistance to streptogramins A and pleuromutilins (L/LSA/LSAP phenotypes).

Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae.

Unlabelled: β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance.