Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus aureus
Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus aureus
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DOI：
10.1093/jac/dkn106
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发表时间：
2008-06-01
影响因子：
5.2
通讯作者：
Sugai, Motoyuki
中科院分区：
文献类型：
--
作者：
Ouhara, Kazuhisa;Komatsuzawa, Hitoshi;Sugai, Motoyuki
目的：研究临床分离的金黄色葡萄球菌，包括耐甲氧西林金黄色葡萄球菌（MRSA）对宿主来源的阳离子抗菌肽的敏感性。方法：检测190株甲氧西林敏感金黄色葡萄球菌（MSSA）和304株MRSA临床菌株对两类阳离子抗菌肽的敏感性：LL-37和人β -防御素-3 （hBD3）。在总共494株临床菌株中，随机选择54株金黄色葡萄球菌进行检测，以建立每个菌株的净电荷或zeta电位与其对hBD3或LL-37的易感性之间的关系。为了进一步确认细菌对hBD3或LL-37的敏感性，我们同时测量了：(i)体外细菌暴露后的存活率和（ii） MRSA和MSSA菌株的MBCs。结果：在随机选取的54株金黄色葡萄球菌中，耐LL-37的MRSA菌株的zeta电位显著高于耐LL-37的MRSA菌株（P < 0.05）。相比之下，对hBD3耐药或敏感的MRSA菌株的细菌zeta电位没有差异。此外，与MSSA菌株相比，高甲氧西林耐药菌株对LL-37的耐药性显著升高（P < 0.01），但对hBD3的耐药性未显著升高（以存活率或MBC测定）。结论：净电荷增加的MRSA临床菌株（而非MSSA）也表现出对LL-37的抗性升高，但对hBD3的抗性没有升高。
Objectives: The susceptibility of clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), to host-derived cationic antimicrobial peptides was investigated.Methods: We examined the susceptibility of 190 clinical strains of methicillin-susceptible S. aureus (MSSA) and 304 strains of MRSA to two different classes of cationic antimicrobial peptides: LL-37 and human beta-defensin-3 (hBD3). Out of the total 494 clinical strains, a random selection of 54 S. aureus strains was examined to establish the relationship between the net charge, or zeta potential, of each strain and its susceptibility to hBD3 or LL-37. To further confirm bacterial susceptibility to either hBD3 or LL-37, we concurrently measured: (i) percentage survival after in vitro bacterial exposure and (ii) MBCs for both MRSA and MSSA strains.Results: Of the 54 randomly selected S. aureus strains, those MRSA strains resistant to LL-37 showed significantly higher zeta potentials than those susceptible to LL-37 (P < 0.05). In contrast, there was no difference in bacterial zeta potentials for MRSA strains that showed either resistance or susceptibility to hBD3. In addition, resistance to LL-37, but not to hBD3, as determined by either percentage survival or MBC, was significantly elevated in highly methicillin-resistant strains of S. aureus when compared with MSSA strains (P < 0.01).Conclusions: Clinical strains of MRSA, but not MSSA, that demonstrated an increased net charge also showed elevated resistance to LL-37, but not to hBD3.