Genomic characterization of Haemophilus influenzae harbouring an exogenous resistance gene

<b>Introduction.</b> Reports of β-lactamase-producing <i>Haemophilus influenzae</i> are increasing worldwide.<b>Aim</b>. This study aimed to elucidate the molecular characteristics and evolution of β-lactamase-producing <i>H. influenzae</i>.<b>Methodology.</b> A total of 159 clinical isolates were characterized using multi-locus sequence typing. Antimicrobial resistance genes and integrative and conjugative element (ICE) types were identified through PCR and DNA sequencing. The genetic structure of ICE was further investigated using whole-genome sequencing.<b>Results.</b> Out of 159 clinical isolates, 20.8% (<i>n</i>=33) were β-lactamase producers. Thirteen sequence types (STs) were identified. ST 103, 155, 165 and 388 have been identified in previous studies, suggesting that strains with these STs tend to acquire the β-lactamase gene <i>bla</i> _TEM-1. Among β-lactamase producers, 66.7% (<i>n</i>=22) of <i>bla</i> _TEM-1 were located on ICE. The ICEs could be classified into two groups based on their sequence (types I and II). Among these strains, 2017-Y3 harboured a macrolide resistance gene, <i>mef (A/E)</i>, in ICE. A comparative analysis of the ICE region of this strain and those from other countries suggested that each isolate was derived from ICE type I or II. These regions, including <i>mef (A/E</i>), were similar to those of Tn<i>6822</i>, which is commonly found in <i>Streptococcus</i>.<b>Conclusions.</b> This study revealed several STs associated with the acquisition of β-lactamase genes on ICEs. Additionally, ICE evolution involved the acquisition of exogenous genes. The accumulation of resistance genes in ICE raises concerns regarding the emergence of multidrug-resistant <i>H. influenzae</i>.