Heteroresistance to penicillin in Streptococcus pneumoniae
Heteroresistance to penicillin in Streptococcus pneumoniae
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DOI：
10.1073/pnas.0702377104
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发表时间：
2007-08-28
影响因子：
11.1
通讯作者：
Muehlemann, Kathrin
中科院分区：
文献类型：
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作者：
Morand, Brigitte;Muehlemann, Kathrin
对-内酰胺类抗生素的异耐药主要是葡萄球菌，它使诊断程序和治疗成功变得复杂。本研究探讨肺炎链球菌是否存在对青霉素的异源耐药。种群分析（PAP）显示，从当地监测项目获得的9株临床肺炎球菌菌株中，有4株（代表多重耐药克隆ST179、ST276和ST344）和16株参考菌株中的7株(代表国际克隆西班牙(23F)-1、西班牙(9v)-3、西班牙(14)-5、匈牙利(19A)-6、南非(19A)-13、台湾（23F)-15和芬兰(6B)-12）存在较高的青霉素耐药亚群。异耐药菌株的青霉素最低抑制浓度（mic）（大多数细胞）在中高水平范围内（0.19-2.0 μ g/ml）。PAP曲线显示高度耐青霉素菌株台湾(19F)-14、波兰(23F)-16、CSR19A-11和CSR14-10也存在亚群。具有较高青霉素耐药性的细菌亚群的PAP表现出向较高青霉素耐药水平的转变，这种转变在无抗生素培养基上多次传代后恢复。收敛到同型抗性表型没有发生。对两株克隆ST179的比较显示，异抗表型分别与较高的青霉素MIC和较多改变的青霉素结合蛋白（PBP1a、-2b和-2x）相关。因此，国际多重耐药肺炎链球菌克隆中出现了对青霉素的异耐药。肺炎球菌可能利用对青霉素的异源耐药作为其向高度青霉素耐药进化的工具，因为它使细菌有机会在获得耐药基因之前在抗生素存在的情况下探索生长。
Heteroresistance to beta-lactam antibiotics has been mainly described for staphylococci, for which it complicates diagnostic procedures and therapeutic success. This study investigated whether hetero-resistance to penicillin exists in Streptococcus pneumoniae. Population analysis profile (PAP) showed the presence of subpopulations with higher penicillin resistance in four of nine clinical pneumococcal strains obtained from a local surveillance program (representing the multiresistant clones ST179, ST276, and ST344) and in seven of 16 reference strains (representing the international clones Spain(23F)-1, Spain(9v)-3, Spain(14)-5, Hungary(19A)-6, South Africa(19A)-13, Taiwan(23F)-15, and Finland(6B)-12). Heteroresistant strains had penicillin minimal inhibitory concentrations (MICs) (for the majority of cells) in the intermediate- to high-level range (0.19-2.0 mu g/ml). PAP curves suggested the presence of subpopulations also for the highly penicillin-resistant strains Taiwan(19F)-14, Poland(23F)-16, CSR19A-11, and CSR14-10. PAP of bacterial subpopulations with higher penicillin resistance showed a shift toward higher penicillin-resistance levels, which reverted upon multiple passages on antibiotic-free media. Convergence to a homotypic resistance phenotype did not occur. Comparison of two strains of clone ST179 showed a correlation between the heteroresistant phenotype and a higher-penicillin MIC and a greater number of altered penicillin-binding proteins (PBP1a, -2b, and -2x), respectively. Therefore, heteroresistance to penicillin occurs in international multiresistant clones of S. pneumoniae. Pneumococci may use heteroresistance to penicillin as a tool during their evolution to high penicillin resistance, because it gives the bacteria an opportunity to explore growth in the presence of antibiotics before acquisition of resistance genes.