Modelling persistentMycoplasma pneumoniaeinfection of human airway epithelium

Abstract

Mycoplasma pneumoniae is a human respiratory tract pathogen causing acute and chronic airway disease states that can include long-term carriage and extrapulmonary spread. The mechanisms of persistence and migration beyond the conducting airways, however, remain poorly understood. We previously described an acute exposure model using normal human bronchial epithelium (NHBE) in air-liquid interface culture, showing that M. pneumoniae gliding motility is essential for initial colonisation and subsequent spread, including localisation to epithelial cell junctions. We extended those observations here, characterizing M. pneumoniae infection of NHBE for up to 4 weeks. Colonisation of the apical surface was followed by pericellular invasion of the basolateral compartment and migration across the underlying transwell membrane. Despite fluctuations in transepithelial electrical resistance and increased NHBE cell desquamation, barrier function remained largely intact. Desquamation was accompanied by epithelial remodelling that included cytoskeletal reorganisation and development of deep furrows in the epithelium. Finally, M. pneumoniae strains S1 and M129 differed with respect to invasion and histopathology, consistent with contrasting virulence in experimentally infected mice. In summary, this study reports pericellular invasion, NHBE cytoskeletal reorganisation, and tissue remodelling with persistent infection in a human airway epithelium model, providing clear insight into the likely route for extrapulmonary spread.

Unresolved atelectasis in refractory Mycoplasma pneumoniae pneumonia: Predictive factors and the influence of corticosteroids and bronchoscopy lavage therapy

“…To our knowledge, only a few studies mainly Chinese studies have reported of the effective and well-tolerated BLT and bronchoscopy ndings such as mucus plugs on the early stage of RMPP [14,17,[26][27][28] . It has been reported that airway hypersecretion, epithelial desquamation, and remodeling cause AO in a human airway epithelium model with M. pneumoniae infection [29] . MP induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways [30] .…”

Sialylated Receptor Setting Influences Mycoplasma pneumoniae Attachment and Gliding Motility

“…This likely interplay between P1 adhesin complexes and sialic acids having diverse linkages and presentations on airway epithelium could have a profound impact on mycoplasma localization and mobilization in different regions of the conducting airways, depending on the relative abundance of each sialyl linkage. To illustrate, M. pneumoniae attaches to the tips of cilia on NHBE cells, migrates rapidly to the base of the cilia, spreads laterally more slowly, localizing to intercellular junctions, and invades the basolateral compartment (Prince et al, ). The local receptor environment, specifically the relative abundance of oligosaccharide receptors that support or are barriers to adherence and gliding, could account for this colonization pattern.…”

“…of cilia on NHBE cells, migrates rapidly to the base of the cilia, spreads laterally more slowly, localizing to intercellular junctions, and invades the basolateral compartment (Prince et al, 2014(Prince et al, , 2017. The local receptor environment, specifically the relative abundance of oligosaccharide receptors that support or are barriers to adherence and gliding, could account for this colonization pattern.…”

Modelling persistent Mycoplasma pneumoniae biofilm infections in a submerged BEAS-2B bronchial epithelial tissue culture model

“…pneumoniae by the biofilm mode of growth in vivo unclear. Moreover, the interplay between pathogen and host cell has been studied in the context of an acute infection [10] as well as a chronic infection [11], but neither study investigated the roles that the biofilm lifestyle plays during infection.…”