Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
Pathog Dis. 2014 Aug;71(3):326-35. doi: 10.1111/2049-632X.12177. Epub 2014 Apr 28.
Biofilms are involved in the recalcitrance of infections due to the presence of persister cells. Although the molecular basis of persistence is still largely unknown, toxin-antitoxin modules (TA) are thought to play a role in this process. In this study, we investigated whether TA modules contribute to persistence toward antibiotics in Burkholderia cenocepacia J2315. Sixteen pairs of genes were identified based on their apparent similarity to TA modules. Overexpression of the putative toxins had various effects on growth, persistence, and biofilm formation. Toxins, whose overexpression resulted in growth inhibition, often increased the number of surviving persisters; in contrast, overexpression of putative toxins showing no effects on growth had no positive influence on the number of surviving persisters. Furthermore, the expression of the TA modules was compared between treated and untreated sessile and planktonic wild-type cultures. For 10 toxin-encoding genes, the expression was higher in untreated sessile cells than in untreated planktonic cells. Nine toxin-encoding genes were upregulated after treatment with tobramycin, but none after treatment with ciprofloxacin. These results indicate that most, but not all TA modules contribute to persistence in B. cenocepacia J2315 and that this contribution depends on the mode of growth and the antibiotic used.
生物膜的存在导致了感染的顽固，这是由于持久细胞的存在。尽管持久性的分子基础在很大程度上仍然未知，但毒素-抗毒素模块（TA）被认为在这个过程中起作用。在这项研究中，我们研究了 TA 模块是否有助于伯克霍尔德菌中抗生素的持久性。根据它们与 TA 模块的明显相似性，确定了 16 对基因。推测毒素的过表达对生长、持久性和生物膜形成有各种影响。过表达导致生长抑制的毒素通常会增加存活的持久细胞的数量；相比之下，过表达对生长没有影响的推测毒素对存活的持久细胞的数量没有积极影响。此外，还比较了处理和未处理的固定和浮游野生型培养物中 TA 模块的表达。对于 10 个编码毒素的基因，未处理的固定细胞中的表达高于未处理的浮游细胞。妥布霉素处理后有 9 个编码毒素的基因上调，但环丙沙星处理后没有。这些结果表明，大多数但不是所有的 TA 模块都有助于伯克霍尔德菌 J2315 的持久性，而且这种贡献取决于生长方式和使用的抗生素。
