Heterogeneous Streptomycin Resistance Level Among Mycobacterium tuberculosis Strains From the Same Transmission Cluster.
Heterogeneous Streptomycin Resistance Level Among Mycobacterium tuberculosis Strains From the Same Transmission Cluster.
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DOI：
10.3389/fmicb.2021.659545
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发表时间：
2021
影响因子：
5.2
通讯作者：
Osório NS
中科院分区：
文献类型：
--
作者：
Rocha DMGC;Magalhães C;Cá B;Ramos A;Carvalho T;Comas I;Guimarães JT;Bastos HN;Saraiva M;Osório NS
对二线结核病（TB）药物链霉素的广泛和频繁耐药，表明低适应度成本链霉素耐药突变正在持续传播。为了调查这一假设，我们研究了来自葡萄牙结核病流行的681人的队列。全基因组测序（WGS）分析与培养基和小鼠骨髓源性巨噬细胞的表型生长研究相结合。该队列中最常见的耐药是链霉素，占耐药结核分枝杆菌分离株的82.7% （n = 67）。149株临床分离株的WGS鉴定出13个传播聚集性，其中3个聚集性仅含有耐链霉素菌株。最大的集群由8株链霉素耐药菌株组成，最多有5对单核苷酸多态性差异。有趣的是，尽管它们的基因相似，但这些分离株对链霉素的抗性水平不同，这是在培养基和受感染的小鼠骨髓来源的巨噬细胞中测量的。这种表型的遗传基础是gid和其他基因突变的组合。这项研究表明，特定的链霉素耐药突变在队列中传播，耐药菌株在集群水平上进化，允许低到高的链霉素耐药水平，而不需要显着的适应度成本。这不仅与更好地了解以4系结核分枝杆菌感染为主的临床环境中链霉素耐药性的传播有关，而且主要是因为它为研究耐药性的选择和传播开辟了新的前景。
Widespread and frequent resistance to the second-line tuberculosis (TB) medicine streptomycin, suggests ongoing transmission of low fitness cost streptomycin resistance mutations. To investigate this hypothesis, we studied a cohort of 681 individuals from a TB epidemic in Portugal. Whole-genome sequencing (WGS) analyses were combined with phenotypic growth studies in culture media and in mouse bone marrow derived macrophages. Streptomycin resistance was the most frequent resistance in the cohort accounting for 82.7% (n = 67) of the resistant Mycobacterium tuberculosis isolates. WGS of 149 clinical isolates identified 13 transmission clusters, including three clusters containing only streptomycin resistant isolates. The biggest cluster was formed by eight streptomycin resistant isolates with a maximum of five pairwise single nucleotide polymorphisms of difference. Interestingly, despite their genetic similarity, these isolates displayed different resistance levels to streptomycin, as measured both in culture media and in infected mouse bone marrow derived macrophages. The genetic bases underlying this phenotype are a combination of mutations in gid and other genes. This study suggests that specific streptomycin resistance mutations were transmitted in the cohort, with the resistant isolates evolving at the cluster level to allow low-to-high streptomycin resistance levels without a significative fitness cost. This is relevant not only to better understand transmission of streptomycin resistance in a clinical setting dominated by Lineage 4 M. tuberculosis infections, but mainly because it opens new prospects for the investigation of selection and spread of drug resistance in general.
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影响因子：
3.7
作者：
Jagielski T;Ignatowska H;Bakuła Z;Dziewit Ł;Napiórkowska A;Augustynowicz-Kopeć E;Zwolska Z;Bielecki J
通讯作者：
Bielecki J
影响因子：
30.8
作者：
Holt KE;McAdam P;Thai PVK;Thuong NTT;Ha DTM;Lan NN;Lan NH;Nhu NTQ;Hai HT;Ha VTN;Thwaites G;Edwards DJ;Nath AP;Pham K;Ascher DB;Farrar J;Khor CC;Teo YY;Inouye M;Caws M;Dunstan SJ
通讯作者：
Dunstan SJ
影响因子：
4.2
作者：
Ballif M;Harino P;Ley S;Coscolla M;Niemann S;Carter R;Coulter C;Borrell S;Siba P;Phuanukoonnon S;Gagneux S;Beck HP
通讯作者：
Beck HP
影响因子：
5.2
作者：
Degiacomi G;Sammartino JC;Sinigiani V;Marra P;Urbani A;Pasca MR
通讯作者：
Pasca MR
影响因子：
10.7
作者：
Castro, Rhastin A. D.;Ross, Amanda;Gagneux, Sebastien
通讯作者：
Gagneux, Sebastien