jodyphelan / tbdb

Standard database for the TBProfiler tool
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add gyrB Glu540Asp #31

Closed jodyphelan closed 3 years ago

jodyphelan commented 3 years ago

Comments

The mutation seems to be rare due (not found in wgs database). However multiple studies have found the mutation in clinical isolates and performed MIC testing to elucidate its effects.

Literature evidence

Farhat et al (doi: 10.1128/jcm.02775-15) gyrB E540D was significantly associated with an increase in the MIC of moxifloxacin but not to ofloxacin. We also found that gyrA D89N and gyrB E540D cause differential resistance to moxifloxacin in clinical strains; this is supported by previous allelic exchange experiments for gyrB E540D, where resistance to ofloxacin, ciprofloxacin, and levofloxacin was also tested

Malik et al (doi: 10.1371/journal.pone.0039754) E540D consistently conferred resistance to moxifloxacin only.

Disratthakit et al (10.1128/AAC.00539-16) GyrB-E540D led to a dramatic resistance to later-generation quinolones, including moxifloxacin, gatifloxacin, and sparfloxacin (8- to 16-fold increases in MICs and 8.3- to 11.2-fold increases in 50% inhibitory concentrations [IC50s]). However, GyrB-E540D caused low-level resistance to early-generation quinolones, including ofloxacin, levofloxacin, and ciprofloxacin (2- to 4-fold increases in MICs and 1.5- to 2.0-fold increases in IC50s).

Suggestion

I would suggest adding mutation to the database for moxifloxacin only