Complement Susceptibility in Relation to Genome Sequence of Recent Klebsiella pneumoniae Isolates from Thai Hospitals.
Complement Susceptibility in Relation to Genome Sequence of Recent Klebsiella pneumoniae Isolates from Thai Hospitals.
复制标题
与泰国医院最近分离的克雷伯氏菌分离株的基因组序列有关的补体敏感性。
DOI：
10.1128/msphere.00537-18
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发表时间：
2018-11-07
期刊：
影响因子：
4.8
通讯作者：
Taylor PW
中科院分区：
文献类型：
--
作者：
Loraine J;Heinz E;De Sousa Almeida J;Milevskyy O;Voravuthikunchai SP;Srimanote P;Kiratisin P;Thomson NR;Taylor PW
多重耐药肺炎克雷伯菌是导致医院感染比例增加的原因，并且出现了高毒力肺炎克雷伯菌。肺炎克隆现在在健康个体中引起严重的社区获得性感染。这些细菌擅长绕过免疫防御，大多数在血清中存活和生长;它们避免C′介导的破坏的能力与它们的侵袭潜力相关。在C′级联激活和C5 b-9 MAC稳定沉积到OM上后，发生革兰氏阴性菌的杀灭。对于克雷伯氏菌，突变体和接合子的研究已经将荚膜、脂多糖O-侧链和OM蛋白作为C′抗性的决定因素，尽管这些大分子的确切作用尚不清楚。在这项研究中，我们对164株具有不同C′亲和性的克雷伯菌进行了测序，以确定与耐药相关的基因。我们的结论是，没有一个单一的OM成分可以占阻力，这可能取决于生物物理特性的目标双层。抵抗补体（C′）杀菌作用的能力是克雷伯氏菌属中一种强大但知之甚少的毒力性状。杀死需要激活一个或多个C′途径，在外膜（OM）表面组装C5 b-9膜攻击复合物（MAC），并使MAC渗透到靶双层中。我们询问了来自泰国三家三级医院的164株克雷伯菌分离株的全基因组序列，以寻找编码表面定位大分子的基因，这些大分子被认为在确定C′耐药性中发挥作用。大多数分离株（154/164）被鉴定为肺炎克雷伯菌，收集符合以前建立的人口结构和抗生素耐药模式。序列型（ST）和荚膜（K）型的分布也是全球种群的典型特征。大多数（64%）的菌株对C′有抗性，其余菌株被迅速或缓慢杀死。所有分离株均携带编码荚膜多糖（K抗原）的基因，这些基因与C′耐药密切相关。与之前的报告相反，与C′-敏感分离株相比，C′-耐药分离株产生的胶囊量无差异，血清反应性与高粘液粘性胶囊的存在之间也无任何相关性。同样，也没有指定脂多糖O-侧链或主要OM蛋白的基因的存在之间的相关性。一些毒力因子在C′-抗性菌株中更常见，但被认为反映了克隆ST扩增。因此，在本研究中，没有单一基因解释测序的分离株的C′抗性。重要性多重耐药肺炎克雷伯菌是导致医院感染比例增加的原因，并且出现了高毒力肺炎克雷伯菌。肺炎克隆现在在健康个体中引起严重的社区获得性感染。这些细菌擅长绕过免疫防御，大多数在血清中存活和生长;它们避免C′介导的破坏的能力与它们的侵袭潜力相关。在C′级联激活和C5 b-9 MAC稳定沉积到OM上后，发生革兰氏阴性菌的杀灭。对于克雷伯氏菌，突变体和接合子的研究已经将荚膜、脂多糖O-侧链和OM蛋白作为C′抗性的决定因素，尽管这些大分子的确切作用尚不清楚。在这项研究中，我们对164株具有不同C′亲和性的克雷伯菌进行了测序，以确定与耐药相关的基因。我们的结论是，没有一个单一的OM成分可以占阻力，这可能取决于生物物理特性的目标双层。
Multidrug-resistant Klebsiella pneumoniae is responsible for an increasing proportion of nosocomial infections, and emerging hypervirulent K. pneumoniae clones now cause severe community-acquired infections in otherwise healthy individuals. These bacteria are adept at circumventing immune defenses, and most survive and grow in serum; their capacity to avoid C′-mediated destruction is correlated with their invasive potential. Killing of Gram-negative bacteria occurs following activation of the C′ cascades and stable deposition of C5b-9 MACs onto the OM. For Klebsiella, studies with mutants and conjugants have invoked capsules, lipopolysaccharide O-side chains, and OM proteins as determinants of C′ resistance, although the precise roles of the macromolecules are unclear. In this study, we sequenced 164 Klebsiella isolates with different C′ susceptibilities to identify genes involved in resistance. We conclude that no single OM constituent can account for resistance, which is likely to depend on biophysical properties of the target bilayer. The capacity to resist the bactericidal action of complement (C′) is a strong but poorly understood virulence trait in Klebsiella spp. Killing requires activation of one or more C′ pathways, assembly of C5b-9 membrane attack complexes (MACs) on the surface of the outer membrane (OM), and penetration of MACs into the target bilayer. We interrogated whole-genome sequences of 164 Klebsiella isolates from three tertiary hospitals in Thailand for genes encoding surface-located macromolecules considered to play a role in determination of C′ resistance. Most isolates (154/164) were identified as Klebsiella pneumoniae, and the collection conformed to previously established population structures and antibiotic resistance patterns. The distribution of sequence types (STs) and capsular (K) types were also typical of global populations. The majority (64%) of isolates were resistant to C′, and the remainder were either rapidly or slowly killed. All isolates carried genes encoding capsular polysaccharides (K antigens), which have been strongly linked to C′ resistance. In contrast to previous reports, there were no differences in the amount of capsule produced by C′-resistant isolates compared to C′-susceptible isolates, nor was there any correlation between serum reactivity and the presence of hypermucoviscous capsules. Similarly, there were no correlations between the presence of genes specifying lipopolysaccharide O-side chains or major OM proteins. Some virulence factors were found more frequently in C′-resistant isolates but were considered to reflect clonal ST expansion. Thus, no single gene accounts for the C′ resistance of the isolates sequenced in this study. IMPORTANCE Multidrug-resistant Klebsiella pneumoniae is responsible for an increasing proportion of nosocomial infections, and emerging hypervirulent K. pneumoniae clones now cause severe community-acquired infections in otherwise healthy individuals. These bacteria are adept at circumventing immune defenses, and most survive and grow in serum; their capacity to avoid C′-mediated destruction is correlated with their invasive potential. Killing of Gram-negative bacteria occurs following activation of the C′ cascades and stable deposition of C5b-9 MACs onto the OM. For Klebsiella, studies with mutants and conjugants have invoked capsules, lipopolysaccharide O-side chains, and OM proteins as determinants of C′ resistance, although the precise roles of the macromolecules are unclear. In this study, we sequenced 164 Klebsiella isolates with different C′ susceptibilities to identify genes involved in resistance. We conclude that no single OM constituent can account for resistance, which is likely to depend on biophysical properties of the target bilayer.