Mycoplasmas, the smallest known self-replicating organisms, possess a simple structure, lack a cell wall, and have limited metabolic pathways. They are responsible for causing acute or chronic infections in humans and animals, with a significant number of species exhibiting pathogenicity. Although the innate and adaptive immune responses can effectively combat this pathogen, mycoplasmas are capable of persisting in the host, indicating that the immune system fails to eliminate them completely. Recent studies have shed light on the intricate and sophisticated defense mechanisms developed by mycoplasmas during their long-term co-evolution with the host. These evasion strategies encompass various tactics, including invasion, biofilm formation, and modulation of immune responses, such as inhibition of immune cell activity, suppression of immune cell function, and resistance against immune molecules. Additionally, antigen variation and molecular mimicry are also crucial immune evasion strategies. This review comprehensively summarizes the evasion mechanisms employed by mycoplasmas, providing valuable insights into the pathogenesis of mycoplasma infections.

Mycoplasma pneumoniae can cause severe respiratory tract infections and extrapulmonary diseases, which pose a significant threat to the health of children. Diagnostic methods for M. pneumoniae include isolation and culture, antibody detection, fluorescence quantitative PCR, and so on, but there are various shortcomings in time, cost, convenience, and sensitivity. In this study, we developed a rapid, sensitive, specific, and economical method for the detection of M. pneumoniae, termed the ERA/CRISPR–Cas12a dual system. The system used the high specificity and collateral cleavage activity of the LbCas12a protein, combined with enzymatic recombination amplification (ERA) technology with strong amplification ability, allowing the results to be observed by a portable fluorometer or visualized by the naked eye with a dipstick, which could be obtained in approximately 30 min. The ERA/CRISPR–Cas12a fluorescence and dipstick system were able to detect M. pneumoniae at titers as low as 1 and 100 copies/μL, respectively. The specificity of the two interpretation methods was 100%, and no cross-reaction with other pathogens was observed. In the evaluation of 92 clinical samples, the positive predictive agreements of the ERA/CRISPR–Cas12a fluorescence and dipstick systems with qPCR detection were 100% and 92.86%, respectively. The negative predictive agreements of both methods were 100%. In conclusion, this study established a portable, rapid, low-cost, ultrasensitive, and specific method for the early and rapid diagnosis of M. pneumoniae to meet the needs of on-site rapid detection in primary health institutions.

Mycoplasma genitalium is a newly emerged sexually transmitted disease pathogen and an independent risk factor for female cervicitis and pelvic inflammatory disease. The clinical symptoms caused by M. genitalium infection are mild and easily ignored. If left untreated, M. genitalium can grow along the reproductive tract and cause salpingitis, leading to infertility and ectopic pregnancy. Additionally, M. genitalium infection in late pregnancy can increase the incidence of preterm birth. M. genitalium infections are often accompanied by co-infection with other sexually transmitted pathogens (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and viral infections (Human Papilloma Virus and Human Immunodeficiency Virus). A recent study suggested that M. genitalium plays a role in tumor development in the female reproductive system. However, few studies endorsed this finding. In recent years, M. genitalium has evolved into a new “superbug” due to the emergence of macrolide-and fluoroquinolone-resistant strains leading to frequent therapy failures. This review summarizes the pathogenic characteristics of M. genitalium and the female reproductive diseases caused by M. genitalium (cervicitis, pelvic inflammatory disease, ectopic pregnancy, infertility, premature birth, co-infection, reproductive tumors, etc.), as well as its potential relationship with reproductive tumors and clinical treatment.

Mycoplasma pneumoniae infection often causes respiratory diseases in humans, particularly in children and adults with atypical pneumonia and community-acquired pneumonia (CAP), and is often exacerbated by co-infection with other lung diseases, such as asthma, bronchitis, and chronic obstructive pulmonary disorder. Community-acquired respiratory distress syndrome toxin (CARDS TX) is the only exotoxin produced by M. pneumoniae and has been extensively studied for its ADP-ribosyltransferase (ADPRT) activity and cellular vacuolization properties. Additionally, CARDS TX induces inflammatory responses, resulting in cell swelling, nuclear lysis, mucus proliferation, and cell vacuolization. CARDS TX enters host cells by binding to the host receptor and is then reverse transported to the endoplasmic reticulum to exert its pathogenic effects. In this review, we focus on the structural characteristics, functional activity, distribution and receptors, mechanism of cell entry, and inflammatory response of CARDS TX was examined. Overall, the findings of this review provide a theoretical basis for further investigation of the mechanism of M. pneumoniae infection and the development of clinical diagnosis and vaccines.

Annexin A2 is a Ca²⁺ regulated protein belonging to the Annexin family and is found in the cytoplasm and cell membrane. It can exist in a monomeric form or in a heterotetrameric form with the S100A10 dimer. The research on Annexin A2 in tumours is currently active, and studies on its role in pathogen infection are increasing. Annexin A2 plays a crucial role in the life cycle of viruses by mediating adhesion, internalization, uncoating, transport, and release. In the case of parasites, bacteria, mycoplasma, fungi, and other pathogens, Annexin A2 binds to the ligand on the pathogen, which mediates the pathogen’s adhesion to the host cell, ultimately leading to infection and damage to the host. Furthermore, some studies have developed biological or chemical drugs that target Annexin A2, which have demonstrated promising anti-infective effects. Thus, targeting Annexin A2 may present a promising therapeutic approach for the treatment of diverse infectious diseases. In summary, this paper provides an overview of Annexin A2 and its role in various pathogens. It highlights its regulation of pathogen infection and its potential as a therapeutic target for the treatment of infectious diseases.