Mycoplasma pneumoniae Infections: Pathogenesis and Vaccine Development

Abstract

Mycoplasma pneumoniae is a major causative agent of community-acquired pneumonia which can lead to both acute upper and lower respiratory tract inflammation, and extrapulmonary syndromes. Refractory pneumonia caused by M. pneumonia can be life-threatening, especially in infants and the elderly. Here, based on a comprehensive review of the scientific literature related to the respective area, we summarize the virulence factors of M. pneumoniae and the major pathogenic mechanisms mediated by the pathogen: adhesion to host cells, direct cytotoxicity against host cells, inflammatory response-induced immune injury, and immune evasion. The increasing rate of macrolide-resistant strains and the harmful side effects of other sensitive antibiotics (e.g., respiratory quinolones and tetracyclines) in young children make it difficult to treat, and increase the health risk or re-infections. Hence, there is an urgent need for development of an effective vaccine to prevent M. pneumoniae infections in children. Various types of M. pneumoniae vaccines have been reported, including whole-cell vaccines (inactivated and live-attenuated vaccines), subunit vaccines (involving M. pneumoniae protein P1, protein P30, protein P116 and CARDS toxin) and DNA vaccines. This narrative review summarizes the key pathogenic mechanisms underlying M. pneumoniae infection and highlights the relevant vaccines that have been developed and their reported effectiveness.

Keywords: DNA vaccines; Mycoplasma pneumonia; live vector vaccines; pathogenesis; subunit vaccines; virulence factors; whole-cell vaccine.

Figure 1

Component proteins of the internal structure of attachment organelle and proposed mechanism of movements for gliding in M. pneumoniae. HMW1, HMW2, and HMW3 refer to three high molecular weight (HMW) proteins. The force is generated at the bowl complexes, transmitted through the paired plates, and reaches the P1 adhesin complex in the direction of the yellow arrow. (Based on ideas from Nakane, et al. [58]). Copyright: ©2015. Public Library of Science. Creative Commons Attribution License and disclaimer available from: http://creativecommons.org/licenses/by/4.0/.

Figure 2

Pathogenic mechanisms of M. pneumoniae. (A) Nuclease and IbpM in M. pneumoniae enable immune evasion, and homologous DNA recombination leads to antigen variation; (B) M. pneumoniae adhesion causes cell damage. Additionally, the P1 adhesin protein binds to the sialic acid receptor on the host cell surface contributing to M. pneumoniae adherence and gliding. Furthermore, elongation factor Tu (EF-Tu) can bind strongly to a diverse range of host molecules (such as fibronectin), contributing to adhesion; (C) Inflammation-inducing factors (HapE enzyme, oxidase GlpO, membrane lipids, lipoproteins, and capsular materials) activate host cell inflammatory pathways; (D) M. pneumoniae secretes cytotoxic nuclease (catalytic protein encoded by MPN133) and CARDS toxin.