Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
CIBER de Enfermedades Respiratorias, ISCIII, Madrid, Spain.
J Antimicrob Chemother. 2021 Jul 15;76(8):1991-2003. doi: 10.1093/jac/dkab130.
To phenotypically and genetically characterize the antibiotic resistance determinants and associated mobile genetic elements (MGEs) among macrolide-resistant (MR) Streptococcus pyogenes [Group A streptococci (GAS)] clinical isolates collected in Barcelona, Spain.
Antibiotic susceptibility testing was performed by microdilution. Isolates were emm and MLST typed and 55 were whole-genome sequenced to determine the nature of the macrolide resistance (MR) determinants and their larger MGE and chromosomal context.
Between 1998 and 2018, 142 of 1028 GAS (13.8%) were MR. Among 108 isolates available for molecular characterization, 41.7% had cMLSB, 30.5% iMLSB and 27.8% M phenotype. Eight erm(B)-containing strains were notable in having an MDR phenotype conferred by an MGE encoding several antibiotic resistance genes. MR isolates were comprised of several distinct genetic lineages as defined by the combination of emm and ST. Although most lineages were only transiently present, the emm11/ST403 clone persisted throughout the period. Two lineages, emm9/ST75 with erm(B) and emm77/ST63 with erm(TR), emerged in 2016-18. The erm(B) was predominantly encoded on the Tn916 family of transposons (21/31) with different genetic contexts, and in other MGEs (Tn6263, ICESpHKU372 and one harbouring an MDR cluster called ICESp1070HUB). The erm(TR) was found in ICESp2905 (8/17), ICESp1108-like (4/17), ICESpHKU165 (3/17) and two structures described in this study (IMESp316HUB and ICESp3729HUB). The M phenotype [mef(A)-msr(D)] was linked to phage φ1207.3. Eight integrative conjugative element/integrative mobilizable element (ICE/IME) cluster groups were classified on the basis of gene content within conjugation modules. These groups were found among MGEs, which corresponded with the MR-containing element or the site of integration.
We detected several different MGEs harbouring erm(B) or erm(TR). This is the first known description of Tn6263 in GAS and three MGEs [IMESp316HUB, ICESp3729HUB and ICESp1070HUB] associated with MR. Periods of high MR rates in our area were mainly associated with the expansion of certain predominant lineages, while in low MR periods different sporadic and low prevalence lineages were more frequent.
对从西班牙巴塞罗那采集的大环内酯类耐药（MR）酿脓链球菌[A 组链球菌（GAS）]临床分离株进行抗生素耐药决定因素和相关移动遗传元件（MGE）的表型和遗传特征分析。
采用微量稀释法进行抗生素药敏试验。对分离株进行 emm 和 MLST 分型，对 55 株进行全基因组测序，以确定大环内酯类耐药（MR）决定因素及其更大的 MGE 和染色体背景。
1998 年至 2018 年期间，1028 株 GAS 中有 142 株（13.8%）为 MR。在可进行分子特征分析的 108 株分离株中，41.7%为 cMLSB，30.5%为 iMLSB，27.8%为 M 表型。8 株含有 erm(B)的菌株值得注意，它们具有由编码多种抗生素耐药基因的 MGE 赋予的 MDR 表型。MR 分离株由若干不同的遗传谱系组成，这些谱系由 emm 和 ST 的组合定义。尽管大多数谱系只是暂时存在，但 emm11/ST403 克隆在整个期间都持续存在。emm9/ST75 带有 erm(B)和 emm77/ST63 带有 erm(TR)的两个谱系于 2016-18 年出现。erm(B)主要编码在 Tn916 家族转座子（21/31）上，具有不同的遗传背景，也存在于其他 MGE 中（Tn6263、ICESpHKU372 和一个携带称为 ICESp1070HUB 的 MDR 簇）。erm(TR)存在于 ICEs p2905（17 个中的 8 个）、ICESp1108 样（17 个中的 4 个）、ICESpHKU165（17 个中的 3 个）和本文描述的两个结构（IMESp316HUB 和 ICESp3729HUB）中。M 表型 [mef(A)-msr(D)]与噬菌体 φ1207.3 相关。根据接合模块内基因的含量，将 8 个整合性 conjugative element/integrative mobilizable element（ICE/IME）簇群进行了分类。这些群落在 MGE 中被发现，与包含 erm(B)或 erm(TR)的元素或整合部位相对应。
我们检测到了几个不同的携带 erm(B)或 erm(TR)的 MGE。这是 Tn6263 在 GAS 中的首次已知描述，还有三个 MGE [IMESp316HUB、ICESp3729HUB 和 ICESp1070HUB]与 MR 相关。在我们所在地区大环内酯类耐药率较高的时期，主要与某些主要谱系的扩展有关，而在大环内酯类耐药率较低的时期，不同的散发性和低流行谱系更为常见。
