Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?
2015
Treponema pallidum ssp. pallidum (TPA) causes over 10 million
new cases of syphilis worldwide whereas T. pallidum ssp.
pertenue (TPE), the causative agent of yaws, affects about 2.5
million people. Although penicillin remains the drug of choice
in the treatment of syphilis, in penicillin-allergic patients,
macrolides have been used in this indication since the 1950s.
Failures of macrolides in syphilis treatment have been well
documented in the literature and since 2000, there has been a
dramatic increase in a number of clinical samples with
macrolide-resistant TPA. Scarce data regarding the genetics of
macrolide-resistant mutations in TPA suggest that although
macrolideresistance mutations have emerged independently
several times, the increase in the proportion of TPA strains
resistant to macrolides is mainly due to the spread of
resistant strains, especially in developed countries. The
emergence of macrolide resistance in TPA appears to require a
two-step process including either A2058G or A2059G mutation in
one copy of the 23S rRNA gene and a subsequent gene conversion
unification of both rRNA genes. Given the enormous genetic
similarity that was recently revealed between TPA and TPE
strains, there is a low but reasonable risk of emergence and
spread of macrolide-resistant yaws strains following
azithromycin treatment.
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