Mycobacterium abscessus Smooth and Rough Morphotypes Form Antimicrobial-Tolerant Biofilm Phenotypes but Are Killed by Acetic Acid.
Mycobacterium abscessus Smooth and Rough Morphotypes Form Antimicrobial-Tolerant Biofilm Phenotypes but Are Killed by Acetic Acid.
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DOI：
10.1128/aac.01782-17
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发表时间：
2018-03
影响因子：
4.9
通讯作者：
Hall-Stoodley L
中科院分区：
文献类型：
--
作者：
Clary G;Sasindran SJ;Nesbitt N;Mason L;Cole S;Azad A;McCoy K;Schlesinger LS;Hall-Stoodley L
脓肿分枝杆菌已成为慢性炎症性肺病（如囊性纤维化）患者的重要病原体，最近的报告表明，它可能通过污染物传播。脓肿分枝杆菌表现出两种主要的菌落形态变异：光滑形态（MaSm）和粗糙形态（MaRg）。生物膜的形成、细胞内生存时间的延长和菌落变异的多样性都有助于脓肿分枝杆菌和其他慢性肺部疾病细菌病原体的持续存在。慢性脓肿分枝杆菌感染的普遍模式是，MaSm是一种非侵入性、形成生物膜的持久性表型，而MaRg是一种无法形成生物膜的侵入性表型。我们发现，MaRg具有高聚集性，并形成生物膜样聚集体，与MaSm生物膜聚集体一样，它对酸性ph、过氧化氢（H2O2）以及阿米卡星或阿奇霉素的耐受性明显高于浮游变体。我们进一步表明，这两种变异对人类巨噬细胞样细胞内的抗生素治疗都是难以抵抗的，并且MaRg比MaSm对阿奇霉素更难以抵抗。我们的研究结果表明，生物膜样聚集和延长的细胞内存活可能都有助于这种有问题的病原体在面对抗菌剂时的持久性，无论其形态如何。然而，每个脓肿分枝杆菌变种的生物膜被醋酸迅速杀死，这可能有助于防止局部的污染物传播。
Mycobacterium abscessus has emerged as an important pathogen in people with chronic inflammatory lung diseases such as cystic fibrosis, and recent reports suggest that it may be transmissible by fomites. M. abscessus exhibits two major colony morphology variants: a smooth morphotype (MaSm) and a rough morphotype (MaRg). Biofilm formation, prolonged intracellular survival, and colony variant diversity can each contribute to the persistence of M. abscessus and other bacterial pathogens in chronic pulmonary diseases. A prevailing paradigm of chronic M. abscessus infection is that MaSm is a noninvasive, biofilm-forming, persistent phenotype and MaRg an invasive phenotype that is unable to form biofilms. We show that MaRg is hyperaggregative and forms biofilm-like aggregates, which, like MaSm biofilm aggregates, are significantly more tolerant than planktonic variants to acidic pHs, hydrogen peroxide (H2O2), and treatment with amikacin or azithromycin. We further show that both variants are recalcitrant to antibiotic treatment inside human macrophage-like cells and that MaRg is more refractory than MaSm to azithromycin. Our results indicate that biofilm-like aggregation and protracted intracellular survival may each contribute to the persistence of this problematic pathogen in the face of antimicrobial agents regardless of morphotype. Biofilms of each M. abscessus variant are rapidly killed, however, by acetic acid, which may help to prevent local fomite transmission.