Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB, L'Hospitalet de Llobregat, Barcelona, Spain.
Research Network for Respiratory Diseases (CIBERES), ISCIII, Madrid, Spain.
J Antimicrob Chemother. 2022 Aug 25;77(9):2389-2398. doi: 10.1093/jac/dkac199.
Although pneumococcal conjugate vaccines (PCVs) effectively prevent invasive pneumococcal disease (IPD), serotype replacement has occurred.
We studied the pangenome, antibiotic resistance mechanisms and presence of mobile elements in predominant non-PCV13 serotypes causing adult IPD after PCV13 vaccine introduction in Spain.
We conducted a multicentre study comparing three periods in six Spanish hospitals and analysed through whole genome sequencing representative strains collected in the pre-PCV13, early-PCV13 and late-PCV13 periods.
Among 2197 cases of adult IPD identified, 110 pneumococci expressing non-PCV13 capsules were sequenced. Seven predominant serotypes accounted for 42.6% of IPD episodes in the late-PCV13 period: serotypes 8 (14.4%), 12F (7.5%), 9N (5.2%), 11A (4.1%), 22F (3.9%), 24F (3.9%) and 16F (3.6%). All predominant non-PCV13 serotypes were highly clonal, comprising one or two clonal complexes (CC). In general, CC538, CC4048, CC3016F, CC43322F and CC669N, related to predominant non-PCV13 serotypes, were antibiotic susceptible. CC15611A was associated with resistance to co-trimoxazole, penicillin and amoxicillin. CC23024F was non-susceptible to penicillin and resistant to erythromycin, clindamycin, and tetracycline. Six composite transposon structures of the Tn5252-family were found in CC23024F, CC98912F and CC3016F carrying different combinations of erm(B), tet(M), and cat. Pangenome analysis revealed differences in accessory genomes among the different CC, with most variety in CC3016F (23.9%) and more conservation in CC15611A (8.5%).
We identified highly clonal predominant serotypes responsible for IPD in adults. The detection of not only conjugative elements carrying resistance determinants but also clones previously associated with vaccine serotypes (CC15611A and CC23024F) highlights the importance of the accessory genome.
虽然肺炎球菌结合疫苗（PCV）能有效预防侵袭性肺炎球菌病（IPD），但血清型已发生转变。
我们研究了西班牙引入 PCV13 疫苗后，引起成人 IPD 的非 PCV13 血清型的泛基因组、抗生素耐药机制和移动元件的存在。
我们进行了一项多中心研究，比较了六家西班牙医院的三个时期，并通过全基因组测序分析了 PCV13 疫苗引入前、早期和后期收集的具有代表性的菌株。
在确定的 2197 例成人 IPD 病例中，对表达非 PCV13 荚膜的 110 株肺炎球菌进行了测序。在 PCV13 后期，七种主要血清型占 IPD 发作的 42.6%：血清型 8（14.4%）、12F（7.5%）、9N（5.2%）、11A（4.1%）、22F（3.9%）、24F（3.9%）和 16F（3.6%）。所有主要的非 PCV13 血清型均高度克隆，仅由一个或两个克隆群（CC）组成。一般来说，与主要非 PCV13 血清型相关的 CC538、CC4048、CC3016F、CC43322F 和 CC669N 对抗生素敏感。CC15611A 与复方新诺明、青霉素和阿莫西林耐药有关。CC23024F 对青霉素不敏感，对红霉素、克林霉素和四环素耐药。在 CC23024F、CC98912F 和 CC3016F 中发现了 6 种 Tn5252 家族的复合转座子结构，这些结构携带不同组合的 erm(B)、tet(M)和 cat。泛基因组分析显示，不同 CC 之间的辅助基因组存在差异，CC3016F 的变异最大（23.9%），而 CC15611A 的变异最小（8.5%）。
我们确定了引起成人 IPD 的高度克隆主要血清型。不仅检测到携带耐药决定因素的可接合元件，还检测到与疫苗血清型相关的克隆（CC15611A 和 CC23024F），这突出了辅助基因组的重要性。
