Identification of distinct capsule types associated with Serratia marcescens infection isolates.
Identification of distinct capsule types associated with Serratia marcescens infection isolates.
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DOI：
10.1371/journal.ppat.1010423
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发表时间：
2022-03
期刊：
影响因子：
6.7
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中科院分区：
文献类型：
--
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粘质沙雷菌是一种多用途的机会性病原体，可引起多种感染，包括菌血症。我们之前的工作证实了胶囊多糖（CPS）的生物合成和易位位点有助于粘质葡萄球菌在菌血症小鼠模型和人血清中的存活。在本研究中，我们测定了粘质葡萄球菌（S. marcescens）的荚膜遗传多样性程度。从bbb300s . marcescens基因组序列中提取荚膜位点（KL）并进行比较。KL序列的系统发育比较表明，粘质葡萄球菌（S. marcescens）作为一个物种具有相当程度的KL多样性，并且来自感染分离株的KL序列与来自环境分离株的KL序列之间存在强烈的差异。从鉴定出的5种KL类型中选择菌株进行进一步研究，纯化后的CPS电泳分析表明其产生不同的聚糖。多糖组成分析证实了这一观察结果，并鉴定了各菌株的组成单糖。两个主要的感染相关分支，称为KL1和KL2，从蒴果系统发育中出现。KL1和KL2的菌血症菌株产生酮脱氧壬醛酸和n -乙酰神经氨酸，这两种唾液酸在其他分支的菌株中没有发现。对KL1和KL2序列的进一步研究发现了neuA和neuB两个基因，它们被认为编码唾液酸的生物合成功能。KL1分离物中neuB的破坏导致唾液酸和CPS生产的损失。唾液酸和CPS的缺乏也导致人类单核细胞系对内化的易感性增加，这表明粘质葡萄球菌的吞噬抗性需要CPS。总之，这些结果建立了粘质链球菌的荚膜遗传库，并鉴定了具有唾液酸CPS成分的感染相关分支。粘质沙雷菌是一种具有广泛自然分布的细菌，能够引起感染，特别是在有潜在健康状况的个体中。对于像粘质葡萄球菌这样能够在多种环境中茁壮成长的生物体，需要考虑的一个问题是，特定的遗传谱系是否比其他遗传谱系更适合引起感染。粘质葡萄球菌的荚膜多糖是一种可变的表面结构，对血液感染实验模型中的细菌存活很重要，我们试图确定感染和环境分离的荚膜编码遗传区域内的遗传多样性谱。在这里，我们证明了粘质葡萄球菌菌株源自感染和环境来源分离成不同的分支基于荚膜基因系统发育。分析的大多数感染分离株可进一步分为两种类型。来自两种原发性感染相关胶囊类型的菌株产生唾液酸，这是一种以前未被认识到的特性，可能与胶囊多糖功能和宿主免疫系统识别有关。
Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. Polysaccharide composition analysis confirmed this observation and identified the constituent monosaccharides for each strain. Two predominant infection-associated clades, designated KL1 and KL2, emerged from the capsule phylogeny. Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. Serratia marcescens is a bacterial species with a broad natural distribution that is capable of causing infections, particularly in individuals with underlying health conditions. One consideration for organisms, such as S. marcescens, that can thrive in diverse environments is whether specific genetic lineages are better suited to causing infection than others. The capsular polysaccharide of S. marcescens is a variable surface structure that is important for bacterial survival in an experimental model of bloodstream infection and we sought to determine the spectrum of genetic diversity within the capsule-encoding genetic region among both infection and environmental isolates. Here, we demonstrate that S. marcescens strains originating from infection and environmental sources segregate into distinct clades based on capsule gene phylogeny. The majority of infection isolates analyzed were further differentiated into two types. Strains from both of the primary infection-associated capsule types produce sialic acids, a previously unrecognized trait that is likely to have implications in capsule polysaccharide function and host immune system recognition.
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影响因子：
6.7
作者：
Chang YC;Olson J;Beasley FC;Tung C;Zhang J;Crocker PR;Varki A;Nizet V
通讯作者：
Nizet V
影响因子：
3.2
作者：
Ferrieres, Lionel;Hemery, Gaelle;Ghigo, Jean-Marc
通讯作者：
Ghigo, Jean-Marc
影响因子：
4.9
作者：
Diekema, Daniel J.;Hsueh, Po-Ren;Jones, Ronald N.
通讯作者：
Jones, Ronald N.
影响因子：
3.2
作者：
ANNUNZIATO, PW;WRIGHT, LF;SILVER, RP
通讯作者：
SILVER, RP
影响因子：
2.2
作者：
DOMENICO, P;DIEDRICH, DL;CUNHA, BA
通讯作者：
CUNHA, BA