PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “reduced susceptibility”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Lineage structure and penicillin-binding protein variability in clinical Streptococcus pneumoniae isolates from Southwest China exhibiting reduced susceptibility to penicillin.

BACKGROUND: Reduced susceptibility to penicillin in Streptococcus pneumoniae is mediated primarily by alterations in penicillin-binding proteins (PBPs) and often coexists with multidrug resistance within successful lineages. The region-specific genomic characterization of clinically relevant pneumococci with reduced penicillin susceptibility in Southwest China remains limited. METHODS: We performed whole-genome sequencing of 204 clinical S. pneumoniae isolates collected from five institutions in Southwest China (2018-2022) that met our operational screening definition of reduced susceptibility to penicillin (PEN MIC ≥0.12 μg/mL). Molecular serotypes, MLST types, and Global Pneumococcal Sequence Clusters (GPSCs) were assigned; virulence and antimicrobial resistance determinants were profiled; and a core genome phylogeny was reconstructed with international contextualization through the use of PubMLST genomes meeting the same MIC criterion. Amino acid variability in PBP1a/PBP2b/PBP2x was quantified using TIGR4 numbering, and highly variable noncatalytic residues located within 15 Å of catalytic motifs were prioritized via structure-guided screening. RESULTS: The isolates showed a high burden of resistance to non-β-lactam antibiotics (erythromycin, 98.5%; tetracycline, 82.8%; trimethoprim-sulfamethoxazole, 64.7%), while fluoroquinolone susceptibility was largely preserved (≥97%), and vancomycin/linezolid resistance was not detected. Twenty-seven serotypes were identified, among which 19F (23.5%) and 19A (14.2%) were dominant, and the estimated PCV13 coverage was 69.6%. GPSC1 was the dominant lineage (36.8%), and the lineage composition among our isolates differed markedly from those in the PubMLST-USA and PubMLST-Thailand subsets. Virulence and resistance gene carriage differed markedly between GPSC1 and non-GPSC1 isolates, with enrichment of pilus operons, mef(A)/msr(D), and folA/folP in GPSC1. PBP variations were clustered in transpeptidase domains and motif-adjacent regions while essential catalytic residues were conserved; with the structure-guided filter, 12, 11, and 11 motif-proximal noncatalytic candidate sites were prioritized in PBP1a, PBP2b, and PBP2x, respectively. CONCLUSION: Clinical S. pneumoniae isolates with reduced penicillin susceptibility collected in Southwest China demonstrated resistance and accessory gene profiles that were strongly structured by a GPSC-defined lineage background. Our site-resolved, structure-guided PBP analysis provides a regional PBP variability landscape and a compact set of recurrent motif-proximal candidate substitutions to support surveillance and downstream functional validation.

Streptococcus pneumoniae↗
PubMed2026

Genetic characterization of carbapenem-resistant Klebsiella pneumoniae bloodstream isolates with reduced susceptibility to cefiderocol.

OBJECTIVES: To assess cefiderocol activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream isolates collected before local clinical introduction and to characterize the distribution of borderline MIC elevation across major genomic backgrounds. METHODS: We retrospectively analyzed 389 episodes of K. pneumoniae bloodstream infection at a tertiary hospital in China during 2018-2024. All 83 carbapenem-resistant isolates underwent cefiderocol broth microdilution testing and whole-genome sequencing. For epidemiological analysis, reduced susceptibility was prespecified as an MIC of 4-16 mg/L and was not intended to replace clinical breakpoint interpretation. RESULTS: CRKP accounted for 21.3% of K. pneumoniae bloodstream infections and remained associated with in-hospital mortality after adjustment for infection severity and source. By CLSI criteria, 83.1% of isolates were cefiderocol susceptible; the MIC50 and MIC90 were 4 and 8 mg/L, respectively, and 41.0% met the reduced-susceptibility definition. ST11 predominated, with KL47 and KL64 as the main capsular loci. Cefiderocol MICs were higher among KL47/KL64 and virulence-plasmid-associated isolates than among comparator backgrounds. In multivariable analysis, bla NDM-1, bla SHV-12, and the aerobactin locus remained associated with reduced susceptibility, although the findings require cautious interpretation because of limited sample size and possible effects of clonal background. No inactivating mutations were identified in cirA, fepA, or fiu. CONCLUSIONS: Borderline cefiderocol MIC elevation was present before local drug exposure and was more frequent in locally prevalent ST11-KL47/KL64 and virulence-plasmid-associated CRKP. These findings provide a bloodstream-specific pre-introduction baseline and support prospective surveillance of numerical MIC distributions and associated genomic backgrounds.

Cefiderocol↗
PubMed2026

Transgenic overexpression of GmAPC7-CT improves seed yield and reduces susceptibility to soybean mosaic virus and Meloidogyne incognita in soybean.

Stable transgenic soybean lines overexpressing the GmAPC7-CT gene have demonstrated increased seed yield and reduced susceptibility to the soybean mosaic virus and Meloidogyne incognita. The Anaphase-Promoting Complex subunit 7 (APC7) is a core structural component of the anaphase-promoting complex or cyclosome (APC/C). The terminal region of this AtAPC7 gene has been shown in Arabidopsis thaliana to accumulate more transcripts than the full-length gene. The AtAPC7-CT gene (terminal region of the AtAPC7) encodes a protein with significant homology to a tobacco viral replication inhibitor (IVR). Its stable overexpression in transgenic A. thaliana lines resulted in notable improvements in biomass, seed yield, earliness of vegetative-reproductive transitions, and reduced susceptibility to viruses. In this study, we generated stable transgenic soybean lines overexpressing the GmAPC7-CT gene (terminal region or 3' portion of Glyma.15G096000, corresponding to the AtAPC7-CT) and evaluated seed yield and susceptibility of these lines to soybean mosaic virus and Meloidogyne incognita. The GmAPC7-CT gene is 624 nucleotides long and encodes a 207-amino acid protein with two tetratricopeptide repeat (TPR) domains. GmAPC7-CT showed 100% amino acid identity with full-length GmAPC7, 81.16% identity with AtAPC7-CT, and 87.94% identity with tobacco IVR. Stable transgenic lines demonstrated significant advancements in plant development and seed yield, with the top three lines producing up to 43% more pods, 44% more seeds, and a 16% increase in seed weight. Furthermore, these soybean lines showed up to a 70% reduction in susceptibility to soybean mosaic virus and M. incognita, reflected by decreased viral RNA load and nematode reproduction factor. Collectively, these results support a conserved role of GmAPC7-CT in soybean and AtAPC7-CT in A. thaliana, acting similarly to the tobacco IVR. Thus, our findings underscore the strong biotechnological potential of the GmAPC7-CT gene to improve key agronomic traits in soybean through genetic engineering approaches, including conventional breeding, transgenesis, and genome editing.

Glycine max↗
PubMed1979

Effects of glucocorticosteroids on cultured human skin fibroblasts. III. Transient inhibition of cell proliferation in the early growth stages and reduced susceptibility in later growth stages.

An immediate depression of the rate of cell proliferation occurred upon addition of glucocorticosteroids to cultures of human skin fibroblasts in the early growth stages. A reduced sensitivity or even insensitivity of the fibroblasts to growth inhibition inhibition was found upon the addition of the steroids at later stages of cell growth, when the cell density has increased. The inhibition in the early growth stages is transient and is most pronounced if the cultured medium is not renewed. This transient inhibition is not due to the development of steroid-resistant cell lines, and resembles the effect called tachyphylaxis, as is also observed in vasoconstriction tests.

Betamethasone Valerate↗
PubMed2025

A common DNA deletion altering the 3'UTR of mdr1 is associated with reduced mefloquine susceptibility in P. vivax parasites from Cambodian patients.

Artemisinin-combination therapies (ACTs) are now recommended for the treatment of uncomplicated malaria caused by Plasmodium vivax, the parasite responsible for the majority of malaria infections outside of Africa. We analyzed the genome sequences of 206 P. vivax parasites collected from Cambodian malaria patients and showed that more than 80% of them carried a DNA deletion located immediately downstream of the multidrug resistance 1 gene (mdr1). This 837 bp deletion overlapped with a different deletion present at low frequency in South American isolates, suggesting a functional role despite not altering the coding sequence of mdr1. Using RNA sequencing, we showed that these deletions altered the transcripts expressed from mdr1 and resulted in mRNAs with different 3' untranslated regions. In Cambodian isolates, the deletion was significantly associated with a higher expression of mdr1 and a lower ex vivo susceptibility to mefloquine. Finally, we genotyped 592 Cambodian isolates collected between 2014 and 2024 and showed that the mdr1 deletion increased in frequency in Cambodia since the introduction of mefloquine as ACT partner drug. Overall, these findings indicate that a common deletion of a non-coding sequence affects the transcription, stability, or translation of mdr1 in P. vivax parasites and could mediate reduced susceptibility to antimalarial drug(s) currently used for the treatment of uncomplicated vivax malaria.

Journal Article↗
PubMed2026

Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026.

In 2023/24, A(H1N1)pdm09 influenza viruses with neuraminidase (NA)-S247N emerged in NA-clade C.5.3.3 carrying NA-I223V, spread internationally, then faded. Such double mutants reappeared sporadically in 2024/25. They expanded again in 2025/26 in NA-clade D.3 viruses carrying NA-S247N after acquiring NA-I223V in Europe - notably Spain, the Netherlands, Finland and France, and beyond. Dutch double mutants from both seasons showed median 12- and 13-fold reduced inhibition by oseltamivir. These findings underscore the need for ongoing genomic and phenotypic monitoring of antiviral susceptibility.

Oseltamivir↗
PubMed2025

Ergosterol-depleted clinical isolates of Nakaseomyces glabratus can develop multi-drug resistance without apparent fitness and virulence defects.

OBJECTIVES: Nakaseomyces glabratus (formerly Candida glabrata) is a leading cause of invasive candidiasis and rapidly develops antifungal drug resistance during treatment. An increasing number of clinical isolates shows reduced susceptibility to echinocandins and azoles, leaving amphotericin B (AMB) as a last therapeutic option. Resistance of N. glabratus to this drug is rare and its underlying mechanisms are still not fully understood. Here, we describe two independent multidrug resistant (MDR) bloodstream isolates displaying resistance to AMB and anidulafungin (ANF) as well as a reduced susceptibility to azoles. METHODS: Whole-genome sequencing and sterol profiling were performed on nine clinical N. glabratus isolates which were resistant to ANF and displayed resistance or low susceptibility to fluconazole (FLU) and AMB. The transcriptional response of reference strain CBS138 and an AMBR+ANFR isolate was analyzed by RNA-seq. Furthermore, PDR1 was deleted in the latter isolate to examine its influence on efflux pump gene expression. Additionally, fitness and virulence of the AMBR+ANFR isolate were examined in growth assays and a Galleria mellonella infection model. RESULTS: Loss of function mutations in the genes ERG3 and ERG4 is linked to ergosterol depletion and AMB resistance. Ergosterol depletion also contributed to a Pdr1-mediated up-regulation of ERG and ABC transporter genes which was associated with low FLU susceptibility. The AMBR isolates displayed no fitness defects and one of them was fully virulent in a G. mellonella infection model. CONCLUSIONS: These findings demonstrate that ergosterol depletion in N. glabratus leads to AMB resistance without affecting fitness or virulence.

Journal Article↗
PubMed2025

Molecular insights into carbapenemase-producing Enterobacterales from Senegal.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are an urgent global health threat, especially in resource-limited countries. Here we determined the prevalence and the molecular characteristics of CPE isolated from infections in Dakar, Senegal. METHOD: From January 2019 to December 2020, Enterobacterales with reduced susceptibility to ertapenem (diameter < 25&#x2005;mm) from infections were collected at the Pasteur Institute of Dakar. Carbapenemases were detected using biochemical and immunochromatographical assays. WGS was used to determine resistome, MLST, plasmids, virulence genes and genetic relatedness. RESULTS: Of the 1045 Enterobacterales collected during the study period, 86 had a diameter around ertapenem of <25&#x2005;mm (8%) and 19 were confirmed as CPE (2%). These included Escherichia coli (n&#x200a;=&#x200a;6) [ST410 (n&#x200a;=&#x200a;3), ST405 (n&#x200a;=&#x200a;2) and ST2083], Enterobacter spp. (n&#x200a;=&#x200a;6) [ST231 (n&#x200a;=&#x200a;3), ST245, ST760 and ST960] and Klebsiella spp. (n&#x200a;=&#x200a;5) (ST22, ST25, ST231, ST1535, ST4843), Citrobacter freundii ST22 (n&#x200a;=&#x200a;1) and Citrobacter koseri with unknown ST (n&#x200a;=&#x200a;1). blaOXA-48 (n&#x200a;=&#x200a;7; 35%), blaOXA-181 (n&#x200a;=&#x200a;7; 35%) and blaNDM-5 (n&#x200a;=&#x200a;6; 30%) genes were identified. C. freundii ST22 harboured blaNDM-5, blaOXA-48 and blaCTX-M-15 genes. Some E. coli isolates belonging to the high-risk clone ST410 were closely related (<20 SNPs) to isolates recovered in France from patients returning from Senegal, suggesting transnational spread. In addition, 5/6 carbapenemase-producing E. coli isolates possessed a four amino acid insertion in PBP3, conferring reduced susceptibility to aztreonam/avibactam and cefiderocol. CONCLUSIONS: This study highlights the spread of NDM-5 and OXA-181 in Senegal, and reports the first co-occurrence of NDM-5 and OXA-48 in sub-Saharan Africa. The spread of CPE, especially in high-risk clones, underscores the urgent need for continued surveillance and targeted interventions.

Senegal↗
PubMed2026

Detection and characterization of antiviral-resistant viruses during the influenza season of 2024-25.

UNLABELLED: During the high severity season of 2024-25, CDC with public health partners sequenced and analyzed genomes of >10,000 influenza viruses for antiviral resistance markers. Available sequence-flagged and representative viruses were tested with antivirals using in vitro assays. In the US, three oseltamivir-resistant A(H3N2) viruses had treatment-emergent neuraminidase (NA) mutations, either E119V or R292K. Oseltamivir-resistant A(H1N1)pdm09 viruses with NA-H275Y were detected in 15 states, albeit at a low frequency (0.53%). They belonged to several phylogenetic groups, with hemagglutinin (HA) subclade D.3.1 combined with either NA subclade D.1 or D.2 being most common. Based on shared sequence data, nearly all H275Y viruses from Australia, Canada, and Chile also belonged to these HA and NA subclades. Conversely, most H275Y viruses (68/81) from China belonged to HA subclade C.1.9 and NA subclade D and shared the permissive mutation R257K. Influenza polymerase acidic (PA) mutations conferring 4- to 92-fold decreased baloxavir susceptibility were detected in nine influenza A viruses. Viruses with PA-I38T showed mild attenuation of replicative fitness in three cell lines. Based on available data, NA-H275Y and PA-I38T viruses were collected from patients with no exposure to antivirals. Baseline susceptibility to all US-approved influenza antivirals remained largely unchanged compared to previous seasons. All swine-origin viruses detected in the US had adamantane resistance-conferring marker, M2-S31N, but remained susceptible to other approved antivirals. Monitoring antiviral susceptibility has substantially improved with increased sequencing capacities and bioinformatic support at public health laboratories. Information gained through influenza surveillance has been used to guide recommendations on antiviral use. IMPORTANCE: Circulation of influenza viruses with reduced susceptibility to antivirals can diminish the usefulness of medications prescribed for influenza. This study informs on the prevalence of drug-resistant influenza viruses in the US during the high severity season of 2024-25. It provides information on susceptibility profile to all approved antiviral medications and on replicative fitness of representative drug-resistant viruses. Most drug-resistant viruses were collected from patients who were not exposed to antivirals indicating their ability to transmit from human to human. Whole-genome sequence (WGS)-based analysis is the cornerstone for surveillance, and numerous laboratories have been utilizing this approach. However, CDC laboratory is the only laboratory in the US conducting phenotypic testing of circulating viruses needed to confirm the outcomes of sequence-based analysis and to identify new molecular markers of resistance. Data gathered through virologic surveillance give much-needed information on drug susceptibility of influenza viruses which are used to guide recommendations on antiviral use.

Antiviral Agents↗
PubMed2026

The inoculum effect of methicillin-susceptible Staphylococcus aureus on cefazolin and other antimicrobial agents.

UNLABELLED: The inoculum effect (IE) refers to a reduced susceptibility of methicillin-susceptible Staphylococcus aureus (MSSA) to certain antibiotics under high bacterial inocula and may contribute to treatment failure. This exploratory study assessed IE prevalence among 234 nonduplicate MSSA isolates across 11 agents spanning major therapeutic classes, including cefazolin, and characterized IE-positive clones via whole-genome sequencing to inform clinical strategies. Minimum inhibitory concentrations (MICs) were determined by broth microdilution at standard and high inocula. Whole-genome sequencing was performed on IE-positive strains to identify &#x3b2;-lactamase types and conduct multilocus sequence typing. The highest prevalence of IE was observed for trimethoprim-sulfamethoxazole (9.4%), followed by erythromycin (8.8%), linezolid (6.8%), penicillin (6.1%), clindamycin (5.5%), vancomycin (3.8%), cefazolin (3.0%), levofloxacin (1.5%), tetracycline (0.5%), and oxacillin and gentamicin (0.0%). All cefazolin IE-positive strains carried blaZ type A, and ST25 was the most common sequence type (42.9%). For trimethoprim-sulfamethoxazole, erythromycin, and clindamycin IE, ST7 was the most common sequence type (22.7%, 26.7%, and 33.3%, respectively). ST1281 and ST188 were the predominant sequence types among strains exhibiting linezolid IE and vancomycin IE (25.0% and 33.3%, respectively). Among the 234 MSSA strains, 66.7% of ST59, 60.0% of ST25, 58.3% of ST5, and 54.2% of ST7 strains exhibited IE to at least one antimicrobial agent. Cefazolin IE was associated with blaZ type A, and ST5, ST7, ST59, and ST25 were the major sequence types associated with IE across the antimicrobial classes tested. IMPORTANCE: Methicillin-susceptible Staphylococcus aureus (MSSA) can show an inoculum effect on multiple antimicrobial agents, which may reduce antibiotic activity under high-burden conditions. In this study, MSSA isolates from Shanghai exhibited inoculum effects on several commonly used agents, although the overall detection rates were low. Cefazolin inoculum effect was specifically associated with blaZ type A, and several major sequence types were more likely to exhibit this phenotype. These findings improve our understanding of the epidemiology of the inoculum effect in MSSA and may help guide laboratory detection and antimicrobial treatment decisions.

Cefazolin↗
PubMed2026

Clinical and Genomic Insights into the Allodiploid Hybrid Pathogen Aspergillus latus: A Retrospective Case Series.

Aspergillus latus is an emerging cryptic allodiploid hybrid pathogen within Aspergillus section Nidulantes that closely resembles related species and therefore prone to misidentification by routine diagnostic methods. Therefore, its true clinical burden is likely underestimated. In this study, we retrospectively characterized five patients with A. latus infections identified by metagenomic next-generation sequencing (mNGS) at a tertiary hospital in China. Clinical manifestations varied according to host immune status, ranging from a subclinical pulmonary lesion in an immunocompetent individual to aggressive disease in highly immunocompromised patients. Conventional microbiological methods showed limited sensitivity and consistently misidentified the isolates as A. nidulans, whereas mNGS enabled accurate detection of A. latus together with complex co-infections. Three viable clinical isolates were recovered for morphological characterization, antifungal susceptibility testing, and whole-genome sequencing (WGS). All tested isolates demonstrated reduced susceptibility to echinocandins but remained susceptible to mold-active triazoles and amphotericin B. Furthermore, WGS and macrosynteny analyses confirmed their allodiploid hybrid nature, revealing a mosaic genome derived from A. spinulosporus and an A. quadrilineatus-related lineage. Collectively, these findings highlight that A. latus may be missed by routine diagnostic methods and may exhibit a distinct antifungal susceptibility profile. Molecular approaches such as mNGS and WGS may therefore help achieve accurate species-level identification and support targeted antifungal therapy. Given this small retrospective case series, larger prospective and multicenter studies are needed to validate these observations and better define the epidemiology, clinical spectrum, and therapeutic implications of this emerging allodiploid hybrid pathogen.

Retrospective Studies↗
PubMed1977

Inhibition of herpes simplex virus strains isolated from herpetic keratitis by polyinosinic acid-polycytidylic acid.

Fifty strains of herpes simplex virus, isolated from patients with herpetic keratitis, were examined in vitro for susceptibility to polyinosinic acid-polycytidylic acid [poly(I:C)] in the presence of a constant concentration of diethylaminoethyl-dextran. The minimal inhibitory concentration of poly(I:C) for 44 of these strains ranged from 0.0001 to 0.1 mug/ml; for the remaining six strains, the minimal inhibitory concentration stood at 1 to 2 mug/ml. Fifteen isolates from primary infections were more susceptible to poly(I:C) than 35 isolates from recurrent infections. Isolates acquired at different points of a given clinical episode showed similar susceptibilities to poly(I:C). In two patients, isolates from consecutive recurrences of infection exhibited reduced susceptibilities. The implications of the above observations for the therapeutic use of poly(I:C) are discussed.

DEAE-Dextran↗
PubMed2026

The black aspergilli (Aspergillus niger complex) and their role in human, animal, and plant diseases.

SUMMARYThe Aspergillus niger complex, also known as the black aspergilli or section Nigri, comprises a diverse group of filamentous fungi with wide-ranging ecological, industrial, and pathogenic significance. While traditionally associated with food spoilage and industrial fermentation, black aspergilli have emerged as opportunistic pathogens affecting humans, animals, and plants. This review provides a comprehensive synthesis of the taxonomy, ecology, pathogenicity, and antifungal resistance of the A. niger complex. Advances in phylogenetics and whole-genome sequencing have clarified the taxonomy of section Nigri, now comprising six core species in series Nigri. Clinically, A. niger complex is implicated in various conditions, including otomycosis, keratitis, cutaneous infections, onychomycosis, chronic pulmonary aspergillosis, and, less commonly, invasive aspergillosis. In animals, black aspergilli have been isolated from respiratory, cutaneous, and systemic infections, particularly in immunocompromised or stressed hosts. Plant pathogenicity is significant, with A. niger complex contributing to pre- and post-harvest spoilage and producing mycotoxins such as ochratoxin A and oxalic acid. The common finding of elevated minimum inhibitory concentrations (MICs) to triazoles, particularly in both environmental and clinical isolates, raises concern, with underlying mechanisms differing from those characterized in A. fumigatus. Reduced susceptibility is potentially driven by efflux pumps and environmental exposure to azole fungicides. Due to commonly higher MICs, antifungal therapy with itraconazole and isavuconazole may have reduced efficacy, and alternatives such as voriconazole or posaconazole should be considered, guided by susceptibility testing where available. This review emphasizes the need for a One Health approach to managing black aspergilli, integrating surveillance, diagnostics, and targeted interventions across human, veterinary, and agricultural sectors.

Humans↗
PubMed2026

Systematic review of the mutations in the active antigenic site &#xd8; of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site &#xd8; of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site &#xd8;, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p&#xa0;<&#xa0;0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans↗
PubMed2026

Clade-dependent antifungal resistance and susceptibility in Candidozyma auris: A global scoping review.

BACKGROUND: Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungal pathogen that has spread globally since its first identification in 2009 and is now classified as a critical-priority pathogen by the World Health Organization. Distinct genetic clades are associated with variations in geographic distribution, antifungal susceptibility, and resistance mechanisms; however, clade-specific evidence remains fragmented. AIMS: To systematically map global evidence on clade diversity, antifungal susceptibility patterns, resistance mechanisms, and clinical implications of C. auris. METHODS: A scoping review was conducted following PRISMA-ScR guidelines. Peer-reviewed primary studies published between 2009 and September 2025 were included if they reported clade attribution and antifungal susceptibility or resistance data. PubMed/MEDLINE, Scopus, and Web of Science were searched. Two reviewers independently screened studies and extracted data using a standardized form. RESULTS: Of 2050 records identified, 105 studies met inclusion criteria, representing 29 countries and diverse study designs. Whole-genome sequencing was the most common typing method. Antifungal susceptibility varied substantially across clades. High fluconazole resistance was consistently reported (MIC 4 to >256&#x3bc;g/mL). Echinocandins generally retained activity, although reduced susceptibility associated with FKS1 mutations was observed. Resistance mechanisms primarily involved mutations in ERG11, FKS1, and efflux-related genes. Studies also reported challenges in healthcare-associated transmission, environmental persistence, and diagnostic misidentification. CONCLUSIONS: C. auris exhibits marked clade-dependent variability in antifungal susceptibility and resistance mechanisms. These findings support the need for clade-informed interpretation of susceptibility data, standardized surveillance, improved diagnostics, and development of novel antifungal therapies.

Antifungal Agents↗
PubMed1977

Evidence for differences in erythrocyte surface receptors for the malarial parasites, Plasmodium falciparum and Plasmodium knowlesi.

Human erythrocytes lacking various blood group determinants were susceptible to invasion by Plasmodium falciparum including Duffy-negative erythrocytes that are refractory to invasion by Plasmodium knowlesi. Erythrocytes treated with trypsin or neuraminidase had reduced susceptibility of P. falciparum and normal susceptibility to P. knowlesi. Chymotrypsin treatment (0.1 mg/ml) blocked invasion only by P. knowlesi. The differential effect of enzymatic cleavage of determinats from the erythrocyte surface on invasion by these parasites suggests that P. falciparum and P. knowlesi interact with different determinants on the erythrocyte surface.

Chymotrypsin↗
PubMed2026

Functional characterization of SHC-like triterpene cyclase genes in azole response and virulence-related traits of Aspergillus fumigatus.

Aspergillus fumigatus is a major opportunistic fungal pathogen, and increasing azole resistance poses a challenge for aspergillosis treatment. Squalene is an upstream precursor of ergosterol biosynthesis and may also be utilized by SHC-like triterpene cyclases, suggesting a potential link between squalene-associated metabolism, membrane adaptation, and azole response. However, the roles of SHC-like triterpene cyclase genes in A. fumigatus remain unclear. Here, we characterized three candidates, shc1, shc2, and shc3, using comparative bioinformatic analysis, gene deletion, phenotypic assays, azole susceptibility testing, transcriptomics, and host-interaction models. Sequence, genomic-context, phylogenetic, and structural analyses suggested divergence among the three candidates. Individual shc deletion caused limited effects on vegetative growth, whereas loss of shc1 mildly reduced susceptibility to voriconazole and posaconazole, as reflected by twofold MIC increases and lower inhibition rates. Transcriptomic analysis revealed distinct remodeling patterns, with &#x394;shc3 showing the broadest transcriptional changes despite no detectable MIC shift. Targeted metabolite profiling and PI uptake analysis further supported an association between shc deletion, sterol/hopane-type triterpenoid balance, and membrane-associated properties. shc deletion also altered epithelial cell interaction phenotypes, while &#x394;shc1 showed reduced lethality in Galleria mellonella. In clinical isolates, elevated shc transcription was associated with azole-resistant backgrounds. These findings suggest functional diversification among SHC-like triterpene cyclase genes and indicate that shc1 may contribute to azole-associated adaptation and virulence-related traits in A. fumigatus.

Aspergillus fumigatus↗