Skip to main content

Genomic profiling of #cefotaxime-resistant #Haemophilus influenzae from #Norway and #Sweden reveals extensive expansion of virulent #MDR international clones

Image
By G.M.

Abstract

Cefotaxime-resistant Haemophilus influenzae (CRHI) are a global concern, but little is known about their molecular epidemiology. The goal of this study was to perform genomic profiling of 191 CRHI from Norway (n = 183) or Sweden (n = 8) (2006–2018) and assess clonal spread using core genome multilocus sequence typing (cgMLST)-based Life Identification Number (LIN) codes based on whole genome sequencing (Ion Torrent). Cefotaxime resistance was confirmed with broth microdilution minimal inhibitory concentration (MIC), interpreted with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. 35.7% of isolates with cefotaxime gradient MIC of 0.25 mg/L were falsely resistant. All but two isolates (blood) were non-invasive, and all but two (serotype f) were non-typeable. Characterization included calling of resistance determinants, ftsI typing (penicillin-binding protein 3, PBP3), and classification of PBP3-mediated beta-lactam resistance (rPBP3), with assignment to rPBP3 stage and group. All isolates had rPBP3-defining substitutions, and 78.5% were stage 3 (L389F positive). Beta-lactam MICs correlated well with rPBP3 genotypes. Significant proportions of stage 3 isolates were cross-resistant to ceftriaxone (86.0%) and meropenem (meningitis breakpoints, 26.0%). The CRHI prevalence in Norway doubled during the study period and approached 1%. A shift from stage 2 to stage 3 rPBP3 in 2011–2012 led to emergence of CRHI with higher beta-lactam MICs and co-resistance to multiple non-beta-lactams, including extensively drug-resistant (XDR) strains. The shift was driven by transformation with two distinct variants of the transpeptidase region and multiclonal expansion. 66.0% of the isolates belonged to 27 clusters. Ten clusters or singletons belonged to international CRHI clones represented in the PubMLST database. The study provides new insight into CRHI evolution, resistance profiles, and clonal dynamics in a period when this phenotype went from exceptional to unusual in Europe. International CRHI clones are described for the first time, including eight high-risk clones associated with invasive disease, calling for enhanced genomic surveillance. LIN coding, supplemented with ftsI typing and rPBP3 staging, is well-suited for definition of CRHI clones. LIN9, defined by ≤ 10 allelic differences, offered the highest resolution level fully supported by maximum likelihood core genome phylogeny and is proposed as a global standard for genomic surveillance of H. influenzae.

Source: Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1601390/full

____

Labels:

Comments

Post a Comment

Popular posts from this blog

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

By G.M.
{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...
Post a Comment
Read more »

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

By G.M.
Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...
Post a Comment
Read more »

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

By G.M.
Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...
Post a Comment
Read more »