Correlation of Moraxella catarrhalis macrolide susceptibility with the ability to adhere and invade human respiratory epithelial cells

ABSTRACT

Recently, the prevalence of macrolide-resistant Moraxella catarrhalis has been reported, especially among Chinese children. The fitness cost of resistance is reported to render the resistant bacteria less virulent. To investigate the correlation between macrolide susceptibility of M. catarrhalis and pathogenicity, the whole genome of 70 M. catarrhalis isolates belonging to four clonal complexes with different macrolide susceptibilities was sequenced. The gene products were annotated with the Gene Ontology terms. Based on 46 extracted essential virulence genes, 19 representative isolates were selected to infect type II alveolar cells (A549 cells). The ability of these isolates to adhere and invade human epithelial cells and to produce cytokines was comparatively analysed. Furthermore, mice were infected with a pair of M. catarrhalis isolates with different pathogenic behaviours and macrolide susceptibilities to examine pulmonary clearance, histological findings, and the production of cytokines. The percentages of annotations for binding, metabolic process, cellular process, and cell were non-significantly different between the macrolide-resistant and macrolide-susceptible groups. The presence of uspA2, uspA2H, pilO, lbpB, lex1, modM, mboIA, and mboIB significantly differed among the four clonal complexes and macrolide susceptibility groups. Furthermore, compared with those in macrolide-susceptible isolates, the adhesion ability was stronger (P = 0.0019) and the invasion ability was weaker (P < 0.0001) in the macrolide-resistant isolates. Mouse experiments revealed that pulmonary macrophages elicit immune responses against M. catarrhalis infection by significantly upregulating the Csf2, Il4, Il13, Il1b, Il6, Tnf, and Il18. Therefore, M. catarrhalis populations exhibited diverse pathogenicity in vitro and in vivo.

KEYWORDS:

• Moraxella catarrhalis; virulence genes
• adhesion
• invasion
• cytokines
• pathogenicity
• macrolide

Acknowledgments

We thank Catherine Perfect, MA (Cantab) from Liwen Bianji (Edanz) (www.liwenbianji.cn), for the English language editing of the draft manuscript.

Data availability statement

The raw Illumina sequencing reads have been deposited in the Sequencing Read Archive database (https://www.ncbi.nlm.nih.gov/sra) (accession numbers: SRX2447596–SRX2447599, and SRX2161439, SRX2161445, SRX2161448, and SRX2161449).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Beijing Natural Science Foundation: [Grant Number 7214245]; Beijing Key Clinical Specialty for Laboratory Medicine-Excellent Project: [Grant Number ZK201000]; the Fundamental Research Funds for the Central Universities: [Grant Number 2017310002]; the Young Scientific Research Fund of PUMCH: [Grant Number pumch201911291].