Comparative genomic analysis of Mycoplasma pneumoniae isolated in the United Kingdom, between 2016 and 2024.

BACKGROUND: Mycoplasma pneumoniae is a bacterium that causes upper and lower respiratory infections in children and adults. Epidemics occur over the winter period every few years with the most recent seen in 2023/24. These epidemics are thought to be due to the circulation of p1 type variants of M. pneumoniae which have cyclic epidemiology, with the peaks of infection driven by naïve individuals, mainly those < 5-years-old. Currently there is no routine monitoring or genomic surveillance to detect variants of M. pneumoniae circulating in the UK. We analysed 38 genomes of M. pneumoniae isolated in the UK between 2016 and 2024 for the detection of Macrolide-resistant M. pneumoniae (MRMP) and typing of M. pneumoniae variants. Core-genome analysis was used to compare the M. pneumoniae UK data with the global genomic data of 290 M. pneumoniae strains from 14 countries. RESULTS: Of the 38 isolates from UK, the majority were obtained from male patients (62%), with the most common age range (38%) being the 0-15 years age group. All 38 UK isolates were identified as M. pneumoniae, of which 19 isolates (50%) were identified as p1-type 1 strains, and 19 isolates (50%) as p1-type 2. Of 38 isolates, six (16%) isolates were MRMP, of which four (67%) MRMP isolates were identified as sequence type (ST)3 from 2024 and the remaining two MRMP isolates from 2016 to 2024 were identified as ST14. Two core-genome phylogenetic trees; one based on strains from UK only (38 strains) and the other on a combined dataset of global and UK strains (328 strains), revealed two main clades corresponding to p1 types (p1-type 1 and p1-type 2 clades). Within these clades, strains were generally grouped into subclades according to their sequence type (ST), with a few exceptions observed in the global dataset. The phylogenetic tree for the 328 strains (290 global data and 38 UK data) showed 7 Subclades: Subclade 1 (ST3), Subclade 2 (mainly ST3/ST20), Subclade 3 (ST17), Subclade 4 (ST1), Subclade 5 (mainly ST14), Subclade 6 (mainly ST7/ST47) and Subclade 7 (ST2). ST3 strains were positioned in two Subclades (Subclade 1 and Subclade 2). 99% of the isolates in Subclade 1 (ST3) were MRMP. ST3 MRMP includes the most predominant strains in East Asia (Taiwan, Korea, Japan and China). Subclade 1 (ST3) was predominant in the strains isolated in 2024 from the UK that were included in this study out of which three ST3 MRMP strains were clustered in Subclade 1. Macrolide resistance was present in all Subclades except Subclade 7 (ST2). CONCLUSIONS: It is imperative to continuously monitor Subclade 1 in the UK to better understand the burden of macrolide resistance and the potential spread and evolution of this strain within the population. Whole genome sequencing based genomic surveillance of M. pneumoniae is a vital tool for the detection of macrolide resistance, and the surveillance of circulating strains during outbreaks and seasonal epidemic surges.