MOLECULAR BACKGROUND OF FLUOROQUINOLONE RESISTANCE IN PATHOGENIC HUMAN MYCOPLASMAS

Abstract

Human mycoplasma pathogens are resistant to many types of antibiotics because of the lack of a cell wall. Macrolides are most often used for the treatment of mycoplasmosis, but the spread of forms resistant to these antibiotics requires the use of alternative treatment regimens, in particular, the administration of f luoroquinolones and tetracyclines. Of the existing antimicrobial compounds, only f luoroquinolones have a bactericidal effect against mycoplasmas, so use of these antimicrobials is preferable for the treatment of immunosuppressed patients. The limitation of the f luoroquinolones is the resistance of the causative agent to these antimicrobials. Mutations leading to amino acid substitutions in the composition of the targets of f luoroquinolones, gyrase and topoisomerase IV are the most common cause of resistance to f luoroquinolones both in mycoplasms and in other bacteria. It was noted that for mycoplasmas belonging to different species have different patterns of substitutions in the subunits of gyrase and topoisomerase IV. The differences of the structure of these proteins, ref lected in the natural susceptibility to f luoroquinolones in mycoplasmas, may be a reason of this heterogeneity. A number of studies indicate the existence of additional resistance mechanisms, which, first of all, include multiple-resistance systems. Such systems belonging to the ABC-transporter group were also found in mycoplasmas. They are described in Mycoplasma hominis and M. pneumoniae, in M. hominis, their ability to excrete f luoroquinolones from the cells was observed, and in M. pneumoniae the ability of multiple-resistance systems to export macrolides also was noted. Genes encoding components of multiple resistance systems have been found in genomes of other species, including M. genitalium and mycoplasmas, causing animal diseases. Also, in the non-pathogenic for human mycoplasmas Acholeplasma laidlawii, the ability to export proteins and genetic material associated with resistance to f luoroquinolones was found. Understanding the role of the mutations, the activity of transports and their cumulative effect in the development of resistance to f luoroquinolones is particularly important in the context of the determination of resistance to f luoroquinolones in difficult to culture pathogens M. genitalium and M. pneumoniae. Molecular methods for determining the resistance to antimicrobials are now included in clinical practice, but the lack of information about the molecular bases of mycoplasma resistance makes the result insufficiently informative for the pathogens of this group. In the review, the features of the development of resistance to f luoroquinolones in various species of human pathogenic mycoplasmas and their mechanisms at molecular level will be described.

Keywords

• mycoplasmas
• infections
• fluoroquinolone
• resistance
• mutations
• mdr-transporters