Search

Persisters are a sub-population of genetically sensitive bacteria that survive antibiotic treatment by entering a dormant state. The emergence of persisters from dormancy after antibiotic withdrawal leads to recurrent infection. Indole is an aromatic molecule with diverse signalling roles, including a role in persister formation. Here we demonstrate that indole stimulates the formation of Escherichia coli persisters against quinolone antibiotics which target the GyrA subunit of DNA gyrase. However, indole has no effect on the formation of E. coli persisters against an aminocoumarin, novobiocin, which targets the GyrB subunit of DNA gyrase. Two modes of indole signalling have been described: persistent and pulse. The latter refers to the brief but intense elevation of intracellular indole during stationary phase entry. We show that the stimulation of quinolone persisters is due to indole pulse, rather than persistent, signalling. In silico docking of indole on DNA gyrase predicts that indole docks perfectly to the ATP binding site of the GyrB subunit. We propose that the inhibition of indole production offers a potential route to enhance the activity of quinolones against E. coli persisters.

Occasional beer spoilage incidents caused by false-negative isolation of lactic acid bacteria (LAB) in the viable but non-culturable (VBNC) state, result in significant profit loss and pose a major concern in the brewing industry. In this study, both culturable and VBNC cells of an individual Lactobacillus harbinensis strain BM-LH14723 were identified in one spoiled beer sample by genome sequencing, with the induction and resuscitation of VBNC state for this strain further investigated. Formation of the VBNC state was triggered by low-temperature storage in beer (175 ± 1.4 days) and beer subculturing (25 ± 0.8 subcultures), respectively, and identified by both traditional staining method and PMA-PCR. Resuscitated cells from the VBNC state were obtained by addition of catalase rather than temperature upshift, changing medium concentration, and adding other chemicals, and both VBNC and resuscitated cells retained similar beer-spoilage capability as exponentially growing cells. In addition to the first identification of both culturable and VBNC cells of an individual L. harbinensis strain from spoiled beer, this study also for the first time reported the VBNC induction and resuscitation, as well as verification of beer-spoilage capability of VBNC and resuscitated cells for the L. harbinensis strain. Genes in association with VBNC state were also identified by the first genome sequencing of beer spoilage L. harbinensis. The results derived from this study suggested the contamination and spoilage of beer products by VBNC and resuscitated L. harbinensis strain BM-LH14723.

Lactic acid bacteria (LAB) are the most common beer-spoilage bacteria regardless of beer type, and thus pose significant problems for the brewery industry. The aim of this study was to investigate the genetic mechanisms involved in the ability of the hard-to-culture beer-spoilage bacterium Lactobacillus acetotolerans to enter into the viable putative non-culturable (VPNC) state. A genome-wide transcriptional analysis of beer-spoilage L. acetotolerans strains BM-LA14526, BM-LA14527, and BM-LA14528 under normal, mid-term and VPNC states were performed using RNA-sequencing (RNA-seq) and further bioinformatics analyses. GO function, COG category, and KEGG pathway enrichment analysis were conducted to investigate functional and related metabolic pathways of the differentially expressed genes. Functional and pathway enrichment analysis indicated that heightened stress response and reduction in genes associated with transport, metabolic process, and enzyme activity might play important roles in the formation of the VPNC state. This is the first transcriptomic analysis on the formation of the VPNC state of beer spoilage L. acetotolerans.

Long noncoding RNAs (lncRNAs) play critical roles in cellular homeostasis. However, little is known about their effect in developing rat brains with hypoxic-ischemic brain damage (HIBD). To explore the expression and function of lncRNA in HIBD, we analyzed the expression profiles of lncRNAs in hypoxic-ischemic (HI) brains and sham control using microarray analysis. The results showed a remarkable difference in lncRNA between HI and sham brains. A total of 322 lncRNAs were found to be differentially expressed in HI brains, compared to sham control. Among these, BC088414 was one of the most significantly urpregulated lncRNAs. In addition, 375 coding genes were differentially expressed between HI brains and sham control. Pathway and gene ontology analysis indicated that the upregulated coding genes mostly involved in wounding, inflammation and defense, whereas the downregulated transcripts were largely associated with neurogenesis and repair. Moreover, coding non-coding co-expression network analysis showed that the BC088414 lncRNA expression was correlated with apoptosis-related genes, including Casp6 and Adrb2. Silencing of lncRNA BC088414 in PC12 cells caused reduced mRNA level of Casp6 and Adrb2, decreased cell apoptosis and increased cell proliferation. These results suggested lncRNA might participate in the pathogenesis of HIBD via regulating coding genes.