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Spadar, A.

Publications and source records attributed to Spadar, A..

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Uncovering the genetic diversity in Aedes aegypti insecticide resistance genes through global comparative genomics

Insecticides are essential to control the transmission of vector-borne diseases to humans and animals, but their efficacy is being threatened by the spread of resistance across multiple medically important mosquito species. An example of this is Aedes aegypti - a major vector of arboviruses, including Zika, dengue, yellow fever, West Nile, and Chikungunya, with widespread insecticide resistance reported in the Americas and Asia, while data from Africa is more limited. Here we investigate the global genetic diversity in four insecticide resistance associated genes: ace-1, GSTe2, rdl and vgsc. Apart from vgsc, the other genes have been less investigated in Ae. aegypti, and limited genetic diversity information is available. We explore a large whole-genome sequencing dataset of 729 Ae. aegypti across 15 countries including nine in Africa. Among the four genes, we identified 1,829 genetic variants including 474 non-synonymous substitutions, as well as putative copy number variations in GSTe2 and vgsc. Among these are many previously documented insecticide resistance mutations which were present at different frequencies and combinations depending on origin of samples. Global insecticide resistance phenotypic data demonstrated variable resistance in geographic areas with resistant genotypes. These warrant further investigation to assess their functional contribution to insecticide resistant phenotypes and their potential development into genetic panels for operational surveillance. Overall, our work provides the first global catalogue and geographic distribution of known and new amino-acid mutations and duplications that can be used to guide the identification of resistance drivers in Ae. aegypti and thereby support monitoring efforts and strategies for vector control.

genomics↗

Genomic diversity and antimicrobial resistance in clinical Klebsiella pneumoniae isolates from tertiary hospitals in Southern Ghana

Comprehensive data on the genomic epidemiology of hospital-associated Klebsiella pneumoniae in Ghana is scarce. This study sequenced 103 clinical K. pneumoniae isolates from five tertiary hospitals in Southern Ghana, predominantly from paediatric patients under five years (67/103, 65%), with the majority collected from urine (32/103, 31%) and blood (25/103, 24%) cultures. We employed Pathogenwatch for genotyping via Kaptive (K/O antigens) and Kleborate (antimicrobial resistance and hypervirulence) and determined clonal relationships using core-genome multilocus sequence typing (cgMLST). Among the 44 distinct sequence types (STs) detected, ST133 was the most common, comprising 23% of isolates (n=23/103). We discovered 27 different capsular (K) locus antigens and seven lipopolysaccharide (O) types; KL116 (28/103, 27%) and O1 (66/103, 64%) were the most prevalent. Single-linkage clustering highlighted the global spread of multidrug-resistant clones such as ST15, ST307, ST17, ST11, ST101, and ST48, with minimal allele differences (1-5) from publicly available genomes worldwide. Conversely, several isolates (n=17) constituted novel clonal groups and lacked close relatives among publicly available genomes, displaying unique genetic diversity within our study population. A significant proportion of isolates (88/103, 85%) carried resistance genes for three or more antibiotic classes, with the blaCTXM-15 gene present in 78% (n=80/103). Carbapenem resistance, predominantly due to blaOXA-181 and blaNDM-1 genes, was found in 10% (n=10/103) of the isolates. Yersiniabactin was the predominant acquired virulence trait, identified in 70% (n=72/103) of the isolates. Our findings reveal a complex genomic landscape of K. pneumoniae in Southern Ghana, underscoring the critical need for ongoing genomic surveillance to manage the substantial burden of antimicrobial resistance.

genomics↗