Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine‐derived Lysobacter enzymogenes YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction strategy was used to significantly improve the purity to 95.3%. Scanning electron microscopy images revealed that the Type I collagen‐based HSAF (Col‐HSAF) has a transparent appearance and good physical properties, and the in vitro sustained‐release effect of HSAF was maintained for more than 2 weeks. The effective therapeutic concentration of Col‐HSAF against superficial fungal infection was explored, and Col‐HSAF showed good biocompatibility, lower clinical scores, mild histological changes, and antifungal capabilities in animals with Aspergillus fumigatus keratitis and cutaneous candidiasis. In conclusion, Col‐HSAF is an antifungal reagent with significant clinical value in the treatment of superficial fungal infections.
Infections caused by Pseudomonas aeruginosa have become a major public health crisis. Its resistance to existing antibiotics causes clinical infections that are hard to cure. In this study, we found that halogenated indoles in combination with aminoglycoside antibiotics could be more effective than antibiotics alone against P. aeruginosa PAO1 and preliminarily revealed the mechanism of the 4F-indole-induced regulatory effect.
Interspecific and intraspecific communication systems of microorganisms are involved in the regulation of various stress responses in microbial communities. Although the significance of signaling molecules in the ubiquitous family Xanthomonadaceae has been reported, the role bacterial communications play and their internal mechanisms are largely unknown. Here, we use Lysobacter enzymogenes, a member of Xanthomonadaceae, to identify a novel potassium ion import system, LeKdpXFABC. This import system participates in the indole-mediated interspecies signaling pathway and matters in environmental adaptation. Compared with the previously reported kdpFABC of Escherichia coli, LekdpXFABC contains a novel indispensable gene LekdpX and is directly regulated by the indole-related two-component system QseC/B. QseC autophosphorylation is involved in this process. The operon LekdpXFABC widely exists in Xanthomonadaceae. Moreover, indole promotes antimicrobial product production at the early exponential phase. Further analyses show that indole enhances potassium ion adsorption on the cell surface by upregulating the production of O-antigenic polysaccharides. Finally, we confirm that LeKdpXFABC mediation by indole is subject to the intraspecific signaling molecules DSFs, of which the biosynthesis genes always exist together with LekdpXFABC. Therefore, as a new idea, the signal collaborative strategy of indole and DSFs might ensure the persistent fitness advantage of Xanthomonadaceae in variable environments.
A Gram-stain-negative, strictly aerobic, rod-shaped and non-flagellated marine bacterium, designated strain LXI357T, was isolated from deep-sea water sampled at the Tangyin hydrothermal field in the Okinawa Trough. The growth temperature range was 20–45 °C (optimum, 28 °C). Strain LXI357T was also able to grow at pH 5.0–7.5 (optimum, pH 6.0–7.0) and in the presence of 0.5–11 % (optimum, 7%, w/v) NaCl. Strain LXI357T was oxidase-negative and catalase-positive. The predominant fatty acids were C18 : 1 ω7c and C16 : 0. The major polar lipids of strain LXI357T contained phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phospholipid, sphingoglycolipid, diphosphatidylglycero and an unidentified aminolipid. Based on the results of 16S rRNA gene sequence analysis, strain LXI357T belonged to the genus Stakelama and was most closely related to Stakelama flava CBK3Z-3T (96.28%, 16S rRNA gene sequence similarity), followed by Stakelama algicida Yeonmyeong 1-13T (95.67%), Stakelama pacifica JLT832T (95.46%) and Sphingosinicella vermicomposti YC7378T (95.43%). Genome relatedness between strain LXI357T and Stakelama flava CBK3Z-3T was computed using average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity, with values of 76.02, 20.9 and 71.1 %, respectively. The genomic DNA G+C content of strain LXI357T is 64.1 mol%. In addition, strain LXI357T has multiple genes related to sulphur metabolism, including genes encoding for the Sox system. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished strain LXI357T from its closest phylogenetic neighbours. According to the results of polyphasic analyses, strain LXI357T is considered to represent a novel species of the genus Stakelama , for which the name Stakelama marina sp. nov. is proposed. The type strain is LXI357T (=MCCC 1K06076T=KCTC 82726T).
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