Potential for Phages in the Treatment of Bacterial Sexually Transmitted Infections

Abstract

Bacterial sexually transmitted infections (BSTIs) are becoming increasingly significant with the approach of a post-antibiotic era. While treatment options dwindle, the transmission of many notable BSTIs, including Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum, continues to increase. Bacteriophage therapy has been utilized in Poland, Russia and Georgia in the treatment of bacterial illnesses, but not in the treatment of bacterial sexually transmitted infections. With the ever-increasing likelihood of antibiotic resistance prevailing and the continuous transmission of BSTIs, alternative treatments must be explored. This paper discusses the potentiality and practicality of phage therapy to treat BSTIs, including Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Streptococcus agalactiae, Haemophilus ducreyi, Calymmatobacterium granulomatis, Mycoplasma genitalium, Ureaplasma parvum, Ureaplasma urealyticum, Shigella flexneri and Shigella sonnei. The challenges associated with the potential for phage in treatments vary for each bacterial sexually transmitted infection. Phage availability, bacterial structure and bacterial growth may impact the potential success of future phage treatments. Additional research is needed before BSTIs can be successfully clinically treated with phage therapy or phage-derived enzymes.

Keywords: antibiotic resistance; bacteriophage; endolysins; phage therapy; sexually transmitted infections.

Figure 1

Phage/enzymatic action on a variety of cell types (see legend for names of components). Arrows indicate the direction of action of the enzymes during a natural phage infection cycle. Engineered enzymes are shown on the outside of the cells, demonstrating their ability or inability to effectively lyse the cell when applied topically. These schematics represent a general portrayal of phage/enzymatic action on a variety of cell types when each individual interaction with a certain phage, enzyme and cell type can present a more complex exchange. (A) Holin and endolysin activity on a Gram-negative bacterial cell. (B) Holin and endolysin activity on a Gram-positive bacterial cell. (C) Unknown enzyme activity on a mycoplasma. (D) Depolymerase, holin and endolysin activity on a Gram-negative bacterial cell with a capsule and s-layer shown. (E) Depolymerase, holin and endolysin activity on a Gram-positive bacterial cell with a capsule and s-layer shown. (F) Phage activity penetrating a biofilm to infect, replicate within and lyse a bacterial cell. (G) Shown are components of the biofilm, as well as depolymerase activity on the biofilm matrix to perpetuate phage infection into a Gram-positive bacteria cell.