Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 63, Issue 3, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02265-18
Keywords
Mycoplasma genitalium; Mycoplasma pneumoniae; NH125 analogues; Ureaplasma; drug evaluation; nitroxoline; quinoline
Categories
Funding
- NIAID [R01 AI45875]
- National Institute of General Medical Sciences of the National Institutes of Health [R35GM128621]
- National Center for Advancing Translational Sciences of the National Institutes of Health under University of Florida Clinical and Translational Science Awards [TL1TR001428, UL1TR001427]
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Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. To address this shortage, we screened nitroxoline, triclosan, and a library of 20 novel, halogenated phenazine, quinoline, and NH125 analogues against Ureaplasma species and M. hominis clinical isolates from urine. We tested a subset of these compounds (n = 9) against four mycoplasma type strains (M. pneumoniae, M. genitalium, M. hominis, and Ureaplasma urealyticum) using a validated broth microdilution or agar dilution method. Among 72 Ureaplasma species clinical isolates, nitroxoline proved most effective (MIC90, 6.25 mu M), followed by an N-arylated NH125 analogue (MIC90, 12.5 mu M). NH125 and its analogue had significantly higher MICs against U. urealyticum isolates than against U. parvum isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against U. parvum isolates but bacteriostatic activity against the majority of U. urealyticum isolates. Among the type strains, the compounds had the greatest activity against M. pneumoniae and M. genitalium, with 8 (80%) and 5 (71.4%) isolates demonstrating MICs of <= 12.5 mu M, respectively. Triclosan also exhibited lower MICs against M. pneumoniae and M. genitalium. Overall, we identified a promising range of quinoline, halogenated phenazine, and NH125 compounds that showed effectiveness against M. pneumoniae and M. genitalium and found that nitroxoline, approved for use outside the United States for the treatment of urinary tract infections, and an N-arylated NH125 analogue demonstrated low MICs against Ureaplasma species isolates.
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