Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in Haemophilus influenzae

colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in is rare in Europe. In this study, we defined acquired resistance gene loci and mutations in multidrug-resistant (MDR) and/or PBP3-mediated beta-lactam-resistant (rPBP3) strains, intending to understand the mode of spread of antibiotic resistance determinants in this species. Horizontal transfer of mobile genetic elements and transformation with resistance-conferring alleles were contributory. We found one small plasmid and three novel integrative conjugative elements (ICEs) which carry different combinations of resistance genes. Demonstration of transfer and/or ICE circular forms showed that the ICEs are functional. Two extensively MDR genetically unrelated strains (F and G) from the same geographical region shared an identical novel MDR ICE (Tn ) harboring , -like, and (B). The first Nordic case of MDR septicemia, strain 0, originating from the same geographical area as these strains, had a similar resistance pattern but contained another ICE [Tn with , and (B)] with an overall structure quite similar to that of Tn Comparison of the complete genes among rPBP3 strains revealed that the entire gene or certain regions of it are identical in genetically unrelated strains, indicating horizontal gene transfer. Our findings illustrate that is capable of acquiring resistance against a wide range of commonly used antibiotics through horizontal gene transfer, in terms of conjugative transfer of ICEs and transformation of chromosomal genes. colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. As a threat to treatment, resistance against critically important antibiotics is on the rise in Identifying mechanisms for horizontal acquisition of resistance genes is important to understand how multidrug resistance develops. The present study explores the antimicrobial resistance genes and their context in beta-lactam-resistant with coresistance to up to four non-beta-lactam groups. The results reveal that this organism is capable of acquiring resistance to a wide range of commonly used antibiotics through conjugative transfer of mobile genetic elements and transformation of chromosomal genes, resulting in mosaic genes with a broader resistance spectrum. Strains with chromosomally mediated resistance to extended-spectrum cephalosporins, co-trimoxazole, and quinolones combined with mobile gen