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Ribosomal RNA‑depleted RNA sequencing reveals the pathogenesis of refractory Mycoplasma pneumoniae pneumonia in children.

ABSTRACT: Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae) is a major cause of community‑acquired pneumonia in children. In some cases, M. pneumoniae pneumonia (MPP) can develop into refractory MPP (RMPP), which shows no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. However, the pathogenesis of RMPP remains poorly understood. The present study aimed to identify target genes that could be used as biomarkers for the clinical diagnosis of early‑stage RMPP through high‑throughput sequencing technology. The differences in long non‑coding (lnc)RNAs, mRNAs and circular (circ)RNAs were examined between whole‑blood samples from two patients with non‑refractory MPP (NRMPP), two patients with RMPP and three healthy children using ribosomal (r)RNA‑depleted RNA‑sequencing techniques and an integrated mRNA/circRNA analysis. A total of 17 lncRNAs (four upregulated and 13 downregulated), 18 mRNAs (six upregulated and 12 downregulated) and 24 circRNAs (12 upregulated and 12 downregulated) were the most significantly differentially expressed (P<0.05) between the NRMPP and RMPP groups. Upon functional analysis, the significantly differentially expressed genes encoded by the targeting mRNAs (prostaglandin‑endoperoxide synthase 2, IL‑8 and fos‑like antigen 1) were screened and identified to be enriched in the 'IL‑17 signaling pathway'. Furthermore, the key circRNAs in the NRMPP and RMPP comparative groups were primarily enriched in 'herpes simplex virus 1 infection', 'viral carcinogenesis' and 'RNA transport'. In the present study, a comprehensive analysis of the differences between the NRMPP and RMPP cases was performed based on rRNA‑depleted RNA‑sequencing techniques, and the selected genes and circRNAs may be closely associated with the complex pathogenesis of RMPP.

SUBMITTER: Huang F

PROVIDER: S-EPMC8436218 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

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Ribosomal RNA‑depleted RNA sequencing reveals the pathogenesis of refractory Mycoplasma pneumoniae pneumonia in children.

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