Comparison of Isogenic Strains Shows No Evidence of Altered Nosocomial Transmission-Competency of Rough, GPL-Negative Mycobacterium abscessus Strains.
Comparison of Isogenic Strains Shows No Evidence of Altered Nosocomial Transmission-Competency of Rough, GPL-Negative Mycobacterium abscessus Strains.
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DOI：
10.1128/spectrum.01990-21
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
Barkan, Daniel
中科院分区：
文献类型：
--
作者：
Meir, Michal;Foreman, Mark;Bar-Oz, Michal;Naor, Noga;Rozenblit, Anna;Barkan, Daniel
结核分枝杆菌是一种引起严重肺部感染的新兴病原体。虽然起源于环境，但在临床环境中M。脓毒症常转变为与严重非缓解性感染相关的Rough表型。临床分离株的糖肽脂合成基因突变，导致粗糙表型，建议有增加细菌的毒力，同时可能显示出降低的污染物的传播性。我们着手确定是否孤立的糖肽脂（GPL）缺陷影响遗传性。我们使用转座子技术创建完全等基因Rough（GPL缺陷型）（Tn_4099c），并将其与等基因亲本菌株（ATCC 19977）进行比较。通过在指定时间点样、干燥和回收分离株来确定污染物上的存活率。使用差异荧光M. 19977（光滑）和Tn_4099c突变体（粗糙）。使用分枝杆菌的消毒剂消毒试验检测氯己定溶液（Septal Scrub Teva）中的存活能力。尽管在所有的试验中有显著的细菌杀伤作用，我们发现无论是GPL缺陷的粗糙型还是GPL保留的光滑型，在污染物和洗必泰中都没有生存优势。我们的研究结果表明，虽然传输健身可能会改变，由于一些宿主内的进化变化，临床菌株的传播能力下降不能单独归因于GPL合成缺陷。需要进一步的研究来确定其他突变对M传播潜力的影响。在临床环境中的应用。重要性结核分枝杆菌是一种新兴的病原体，可引起严重的肺部感染。在临床上，M.红腹小球藻经历了与毒力增加相关的分子和遗传变化。具体而言，细菌在糖肽脂（GPL）合成中的缺陷，产生了“粗糙”菌落表型，与毒力增加有关，但也可能观察到在污染物上的存活率降低，导致传播性降低。我们着手确定GPL合成缺陷是否确实是导致临床分离株传播性降低的原因。我们比较了完全同基因的GPL破坏与GPL保留菌株，并证明没有生存优势，无论是菌株上的污染物。此外，这两种分离株在洗必泰（一种广泛用于卫生保健环境的消毒剂）中均无存活优势。我们的研究结果表明，临床分离株的传播性降低，如果它被发现，不能归因于GPL合成突变。虽然临床分离株可能显示出传播潜力的变化，但需要更多的研究来调查导致这些表型变化的机制。
Mycobacterium abscessus is an emerging pathogen causing severe pulmonary infections. While environmental in origin, in the clinical setting M. abscessus often changes to a Rough phenotype associated with severe non-remitting infections. Clinical isolates baring mutations in glycopeptidolipid-synthesis genes, leading to the Rough phenotype, were suggested to have increase bacterial virulence while possibly showing reduced transmissibility on fomites. We set to determine whether an isolated glycopeptidolipid (GPL) defect affects transmissibility. We used transposon technology to create a fully isogenic Rough (GPL-defective) (Tn_4099c) and compare it to the isogenic parent strain (ATCC 19977). Survival on fomites was determined by spotting, drying, and retrieving the isolates at designated time points. This was repeated as a competition experiment using a mixture of differentially fluorescent M. abscessus 19977 (Smooth) and the Tn_4099c mutant (Rough). Survival ability in chlorhexidine solution (Septal Scrub Teva) was performed using a disinfectant killing-assay for mycobacteria. Despite significant bacterial killing in all assays, we found no survival advantage to either GPL-defected Rough or GPL-reserved Smooth morphotype—both on fomites and in chlorhexidine. Our findings suggest that while transmission fitness may be altered due to some within-host evolutionary changes, decreased transmissibility of clinical strains cannot be attributed to the GPL-synthesis defect alone. Further studies are needed to determine the effect of other mutations on the transmission potential of M. abscessus in the clinical setting. IMPORTANCE Mycobacterium abscessus is an emerging pathogen causing severe pulmonary infections. In the clinical setting, M. abscsssus undergoes molecular and genetic changes associated with increased virulence. Specifically, bacterial defects in glycopeptidolipid (GPL) synthesis, creating the “Rough” colony phenotype, have been associated with increased virulence, yet were also presumably observed to have decreased survival on fomites, leading to reduced transmissibility. We set to determine whether GPL-synthesis defects are indeed responsible for reduced transmissibility of clinical isolates. We compared fully isogenic GPL-disrupted versus GPL-preserved strains, and demonstrated no survival advantage for either strain on fomites. Additionally, neither isolate had a survival advantage in chlorhexidine, a widely used disinfectant in health care settings. Our findings suggest that reduced transmissibility of clinical isolates, should it be found, cannot be attributed to GPL-synthesis mutations. While clinical isolates may show changes in transmission potential, more studies are needed to investigate the mechanisms leading to these phenotypic changes.
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影响因子：
6.4
作者：
Foreman M;Gershoni M;Barkan D
通讯作者：
Barkan D
DOI：
10.1126/science.abb8699
发表时间：
2021-04-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bryant JM;Brown KP;Burbaud S;Everall I;Belardinelli JM;Rodriguez-Rincon D;Grogono DM;Peterson CM;Verma D;Evans IE;Ruis C;Weimann A;Arora D;Malhotra S;Bannerman B;Passemar C;Templeton K;MacGregor G;Jiwa K;Fisher AJ;Blundell TL;Ordway DJ;Jackson M;Parkhill J;Floto RA
通讯作者：
Floto RA
影响因子：
9.4
作者：
Park, In Kwon;Hsu, Amy P.;Zelazny, Adrian M.
通讯作者：
Zelazny, Adrian M.
影响因子：
4.4
作者：
Robison, RA;Osguthorpe, RJ;Ascenzi, JM
通讯作者：
Ascenzi, JM
影响因子：
4.9
作者：
Clary G;Sasindran SJ;Nesbitt N;Mason L;Cole S;Azad A;McCoy K;Schlesinger LS;Hall-Stoodley L
通讯作者：
Hall-Stoodley L