Antimicrobial Resistance in Clinical Ureaplasma spp. and Mycoplasma hominis and Structural Mechanisms Underlying Quinolone Resistance

Abstract

Antibiotic resistance is a global concern; however, data on antibiotic-resistant Ureaplasma spp. and Mycoplasma hominis are limited in comparison to similar data on other microbes. A total of 492 Ureaplasma spp. and 13 M. hominis strains obtained in Hangzhou, China, in 2018 were subjected to antimicrobial susceptibility testing for levofloxacin, moxifloxacin, erythromycin, clindamycin, and doxycycline using the broth microdilution method. The mechanisms underlying quinolone and macrolide resistance were determined. Meanwhile, a model of the topoisomerase IV complex bound to levofloxacin in wild-type Ureaplasma spp. was built to study the quinolone resistance mutations. For Ureaplasma spp., the levofloxacin, moxifloxacin, and erythromycin resistance rates were 84.69%, 51.44%, and 3.59% in U. parvum and 82.43%, 62.16%, and 5.40% in U. urealyticum, respectively. Of the 13 M. hominis strains, 11 were resistant to both levofloxacin and moxifloxacin, and five strains showed clindamycin resistance. ParC S83L was the most prevalent mutation in levofloxacin-resistant Ureaplasma strains, followed by ParE R448K. The two mutations GyrA S153L and ParC S91I were commonly identified in quinolone-resistant M. hominis. A molecular dynamics-refined structure revealed that quinolone resistance-associated mutations inhibited the interaction and reduced affinity with gyrase or topoisomerase IV and quinolones. The novel mutations S21A in the L4 protein and G2654T and T2245C in 23S rRNA and the ermB gene were identified in erythromycin-resistant Ureaplasma spp. As fluoroquinolone resistance in Ureaplasma spp. and Mycoplasma hominis remains high in China, the rational use of antibiotics needs to be further enhanced.

Phenotypic Antimicrobial Susceptibility and Genotypic Characterization of Clinical Ureaplasma Isolates Circulating in Shanghai, China

“…Few previous studies have focused on the individual UPA and UUR distributions in clinical Ureaplasma spp. samples (Kawai et al, 2015;Schneider et al, 2015;Yang et al, 2020). In our study, the positive rate of UPA among clinical Ureaplasma spp.…”

“…However, in Europe and the United States, the macrolide resistance rates of M. pneumoniae are substantially lower than those in Asia (Waites et al, 2017). Second, these overall figures indicate that resistance rates vary significantly among countries; in some instances, there are even dramatic differences within the same country, which may be related to the different strategy or preference of antimicrobials usage in different areas (Yang et al, 2020). Third, another explanation for this variation may be related to the shortcomings of different Mycoplasma testing kits and the reference broth microdilution method currently used to estimate the antimicrobial susceptibility of Ureaplasma spp.…”

“…isolates showing drug resistance to macrolides; while none of the isolates possessed mutations in the 23S rRNA, we found a mutation in the L4 protein gene and two mutations of the L22 protein gene in eight macrolide-resistant UPA isolates. Yang et al (2020) reported double alterations (A121S and T141I) or a single mutation (D66N) in L22 within five strains, including one sample harboring an S21A substitution in L4 at the same time. In addition, Pereyre et al detected two mutations (Lys91Asn and Ala94Asp) in the ribosomal protein L22 and three mutations (Thr70Lys, Gly71Val, and Trp65Arg) in the ribosomal protein L4 (Pereyre et al, 2007); the Lys91Asn mutation in L22 of an erythromycin-resistant UPA isolate was also found in one UPA isolate resistant to erythromycin and roxithromycin and harboring another mutation, Ser81Pro, in our study.…”

Examination of Ureaplasma urealyticum and Mycoplasma hominis in 4082 Chinese patients

“…At present, these two Mycoplasma can cause pyelonephritis, vaginitis, pelvic inflammation, and other diseases, affecting the quality of life of patients. Therefore, once diagnosed, we must give timely and standardized treatment (5). The results of this study showed that the total infection rate of Mycoplasma in 4082 Chinese patients was 38.39%, mainly due to UU single infection, which was not consistent with the results of some research (6-8), indicating some differences in the distribution of Mycoplasma in different areas, which may be due to the use of antibiotics, sampling sites, detection reagents, and laboratory precision level in different areas.…”

Integrating the Human and Animal Sides of Mycoplasmas Resistance to Antimicrobials

“…Considering only studies which used the reliable reference microdilution broth assay from CLSI [93], the rates of levofloxacin-resistant Ureaplasma spp. were 0% between 2007 and 2013 in England and Wales [123], 0.54% between 2017 and 2018 in Wales [124], 1.4% between 2001 and 2006 [125] then 6% between 2015 and 2016 in the USA [126], but 57% between 2007 and 2013 in Japan [127], and 47.5% in 2017-2018 [128] and 84.3% in 2018 in China [129]. Regarding tetracycline resistance, no clinical resistance through the 16S rRNA mutation has been reported in human species and all resistant isolates harbored the tet(M) gene.…”