Infection strategies of mycoplasmas: Unraveling the panoply of virulence factors

Abstract

Mycoplasmas, the smallest bacteria lacking a cell wall, can cause various diseases in both humans and animals. Mycoplasmas harbor a variety of virulence factors that enable them to overcome numerous barriers of entry into the host; using accessory proteins, mycoplasma adhesins can bind to the receptors or extracellular matrix of the host cell. Although the host immune system can eradicate the invading mycoplasma in most cases, a few sagacious mycoplasmas employ a series of invasion and immune escape strategies to ensure their continued survival within their hosts. For instance, capsular polysaccharides are crucial for anti-phagocytosis and immunomodulation. Invasive enzymes degrade reactive oxygen species, neutrophil extracellular traps, and immunoglobulins. Biofilm formation is important for establishing a persistent infection. During proliferation, successfully surviving mycoplasmas generate numerous metabolites, including hydrogen peroxide, ammonia and hydrogen sulfide; or secrete various exotoxins, such as community-acquired respiratory distress syndrome toxin, and hemolysins; and express various pathogenic enzymes, all of which have potent toxic effects on host cells. Furthermore, some inherent components of mycoplasmas, such as lipids, membrane lipoproteins, and even mycoplasma-generated superantigens, can exert a significant pathogenic impact on the host cells or the immune system. In this review, we describe the proposed virulence factors in the toolkit of notorious mycoplasmas to better understand the pathogenic features of these bacteria, along with their pathogenic mechanisms.

Keywords: Mycoplasmas; adhesins; invasive enzymes; metabolites; toxins.

Figure 1.

Schematic diagram of virulence factors in mycoplasmas. Virulence factors in mycoplasmas include invasiveness, toxin-like substances, exotoxins, pathogenic enzymes, and some membrane components. Invasiveness refers to the ability of mycoplasmas to break through the host’s defense function and to settle, reproduce, and spread in vivo; it is mediated by various factors that comprise adhesins and accessory proteins, capsular polysaccharides, invasive enzymes, and biofilms. Toxin-like substances primarily include metabolites generated during the process of proliferation, such as H₂O₂, NH_3, and H₂S. Certain mycoplasmas can also secrete some exotoxins including CARDS TX and hemolysin, as well as express various pathogenic enzymes, such as lipolytic enzymes, peptidases, phosphatases, ecto-ATPases, cytotoxic nucleases and nucleotidases, which are considered important pathogenic factors for mycoplasmas. In addition, some inherent molecules of the cell membrane such as lipids, membrane lipoproteins, and the superantigen produced by M. arthritidis, may also have a significant pathogenic effect on the host cells or the immune system