Genomic characterization of Haemophilus influenzae harbouring an exogenous resistance gene.

Introduction. Reports of β-lactamase-producing Haemophilus influenzae are increasing worldwide. Aim . This study aimed to elucidate the molecular characteristics and evolution of β-lactamase-producing H. influenzae . Methodology. 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. Results. Out of 159 clinical isolates, 20.8% ( n =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 bla _TEM-1 . Among β-lactamase producers, 66.7% ( n =22) of bla _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, mef (A/E) , 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 mef (A/E ), were similar to those of Tn 6822 , which is commonly found in Streptococcus . Conclusions. 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 H. influenzae .