Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species

Abstract

This study aimed to investigate the role of quinolone resistance-determining regions (QRDRs) of DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE) associated with fluoroquinolone resistance. A total of 114 Ureaplasma spp. strains, isolated from clinical female patients with symptomatic infection, were tested for species distribution and susceptibility to four fluoroquinolones. Moreover, we analysed the QRDRs and compared these with 14 ATCC reference strains of Ureaplasma spp. serovars to identify mutations that caused antimicrobial resistance. Our study indicated that moxifloxacin was the most effective fluoroquinolone against Ureaplasma spp. (MIC range: 0.125-32 mg ml 21 ). However, extremely high MICs were estimated for ciprofloxacin (MIC range: 1-256 mg ml 21 ) and ofloxacin (MIC range: 0.5-128 mg ml 21 ), followed by levofloxacin (MIC range: 0.5-64 mg ml 21). Seven amino acid substitutions were discovered in GyrB, ParC and ParE, but not in GyrA. Ser-83RLeu/Trp (C248T/G) in ParC and Arg-448RLys (G1343A) in ParE, which were potentially responsible for fluoroquinolone resistance, were observed in 89 (77.2 %) and three (2.6 %) strains, respectively. Pro-462RSer (C1384T), Asn-481RSer (A1442G) and Ala-493RVal (C1478T) in GyrB and Met-105RIle (G315T) in ParC seemed to be neutral polymorphisms, and were observed and occurred along with the amino acid change of Ser-83RLeu (C248T) in ParC. Interestingly, two novel mutations of ParC and ParE were independently found in four strains. These observations suggest that amino acid mutation in topoisomerase IV appears to be the leading cause of fluoroquinolone resistance, especially the mutation of Ser-83RLeu (C248T) in ParC. Moxifloxacin had the best activity against strains with Ser-83RLeu mutation.

Antibacterial Resistance in Ureaplasma Species and Mycoplasma hominis Isolates from Urine Cultures in College-Aged Females

“…A 2015 study performed in China uncovered the first phenotypic evidence of LVX r associated with an S83W NSS in a U. parvum isolate. Their corresponding MICs (levofloxacin, 4 g/ml; ciprofloxacin, 16 g/ml) matched those of our levofloxacin-resistant isolate (26). Recent studies in the United States, Japan, and England and a review cataloguing mutations in Ureaplasma species isolates from 2006 to 2016 found that the S83L substitution in parC solely accounted for LVX r in the majority of isolates (range, 55 to 87%) examined (17,19,24,25,27).…”

“…Although we detected only one levofloxacin-resistant isolate, it did have an NSS identified only twice previously in Ureaplasma species clinical isolates (25,26). The first report of this mutation surfaced in a Japanese isolate (25); unfortunately, the authors were unable to cultivate the isolate for MIC testing.…”

Spread of multidrug resistance among Ureaplasma serovars, Tunisia

“…However, the newer fluoroquinolones, LVX and MXF presented a greater effectiveness against Ureaplasma spp., as described elsewhere [32]. By contrast, Song et al have reported in China a higher resistance rate to LVX (76.9%) and MXF (23.1%), compared to our findings (17.82 and 0%, respectively) [33]. In our study, all isolates were resistant to ERY and moderately sensitive to AZM, which was surprising as Ureaplasma spp.…”

Current understanding and treatment of intra‐amniotic infection with Ureaplasma spp.

“…High rates of amino acid mutations in DNA gyrase and topoisomerase IV were found in fluoroquinolone ‐ resistant Ureaplasma spp . We isolated Ureaplasma spp.…”