Archives of Microbiology最新文献

Entomopathogenic fungi excrete a group of proteins to assimilate nutrients and defeat the host immune defense. Functional secretory signal sequences are needed for efficient secretion of the virulence-related proteins in recombinant strain. In this study, secretome analysis was used to explore the secreted proteins of Beauveria bassiana. Enrichment analysis indicated that B. bassiana secretome was mainly associated with metabolism of glucoside, polysaccharide, extracellular ester compound, and so on. In addition, proteins associated with biogenesis of cellular components were also enriched, including those involved in biogenesis of cell wall and vacuole. Then, four secretory signal sequences were functionally verified with green fluorescent protein as reporter. Finally, a signal sequence was used to excrete three insect venom protein serpins in B. bassiana, in which over-expression of serpin 8 gene resulted in a significant increase in fungal virulence. This study highlights that functional secretory signal sequences are potential molecular elements useful in excretion of virulence-related proteins in insect pathogenic fungi.

Japanese encephalitis virus (JEV) is a mosquito-borne neurotropic virus that claims thousands of children’s lives globally every year, causing neuropsychiatric sequelae. While neuronal cell pathogenesis is a terminal consequence of JEV infection, the virus hijacks macrophages during initial replication and propagation, making macrophages critical cells of host immune defense that dictate the outcomes of infection. Though a plethora of studies have been reported using various neuronal and immune cells, a global response of human macrophages to JEV infection is yet to be explored. In this study, we assessed the kinetics of global proteome dysregulation employing an in vitro JEV infection model using human monocyte-derived macrophages (THP-1). A comparative assessment of the proteome of the infected THP-1 cells revealed differential regulation of 428 proteins at 24 h post-infection (hpi), which was later increased to 443 by 48 h post-infection. Global gene ontology analysis of the differentially expressed proteins highlighted several critical pathways related to immune and metabolic processes that are known to play either proviral or antiviral effects during infection. Notably, several antiviral proteins, including STAT2, OAS1, MX1, MX2, RIG-I, ISG15, and ISG20, were significantly upregulated at both time points post-infection. In contrast, a considerable downregulation of BCL-2, an anti-apoptotic protein at 48hpi indicates the activation of cell death pathways. Further, gene set enrichment analysis identified the type I interferon signaling pathway as one of the top upregulated pathways following JEV infection in human macrophages. Altogether, this study demonstrates human macrophage responses to JEV infection at the proteome level for the first time, highlighting several critical and novel antiviral proteins and pathways that not only advance our understanding of anti-JEV immunity but also aid in developing strategies to control this acute global public health menace.

The plasmid encoded mobile colistin resistance (MCRs) enzyme poses a significant challenge to the clinical efficacy of colistin, which is frequently employed as a last resort antibiotic for treating infections caused by multidrug resistant bacteria. This transferase catalyzes the addition of positively charged phosphoethanolamine to lipid A of the outer membrane of gram-negative bacteria, thereby facilitating the acquired colistin resistance. This review aims to summarize and critically discuss recent advancements in the distribution and pathogenesis of mcr-positive bacteria, as well as the various control measures available for treating these infections. In addition, the ecology of mcr genes, colistin-resistance mechanism, co-existence with other antibiotic resistant genes, and their impact on clinical treatment are also analyzed to address the colistin resistance crisis. These insights provide a comprehensive perspective on MCRs and serve as a valuable reference for future therapeutic approaches to effectively combat mcr-positive bacterial infections.

Graphical Abstract

To establish efficient yeast cell factories, it is necessary to understand the transcriptional and metabolic changes among different yeasts. Saccharomyces cerevisiae BY4742 and CEN.PK2-1C strains are originated from different yeast strains and are commonly used as model organisms and chassis cells in molecular biology study and synthetic biology-based natural production. Metabolomic analysis showed that the BY4742 strain produced higher levels of phenylalanine, tyrosine than CEN.PK2-1C, while CEN.PK2-1C produced high levels of indoleacetaldehyde, indolepyruvate. Transcriptomic analysis showed that the two strains showed large differences in the glycolysis pathway and pyruvate metabolism pathway. CEN.PK2-1C had greater glycolysis flux than BY4742, whereas BY4742 has greater flux in the pathway of pyruvate metabolism to produce fumarate. These findings provide a basis knowledge of the metabolomic and transcriptomic differences between BY4742 and CEN.PK2-1C strains, and also provide preliminary information for strain selection for molecular biology study and synthetic biology-based natural product production.

Antibiotic-associated diarrhea (AAD) is diarrhea caused by disturbances in intestinal microbiota and metabolism following inappropriate use of antibiotics. With the over-reliance on antibiotics, the incidence of AAD is increasing worldwide. Recently, the role of probiotics and prebiotic preparations in the prevention and treatment of AAD has received increasing attention. Various prebiotics can not only reduce the incidence of AAD, but also effectively shorten the course of the disease and alleviate the symptoms. Notably, many polysaccharides derived from plants and fungi are a class of biologically active and rich prebiotics with great potential to alleviate AAD. Therefore, this review aims to summarize the latest research on natural product polysaccharides to alleviate antibiotic-associated diarrhea by modulating the gut microbiota. It provides a theoretical basis for exploring the mechanism of natural product modulation of gut microbiota to alleviate AAD, and provides a reference for further development of active prebiotics.

Plastics offer versatility, durability and low production costs, but they also pose environmental and health risks due to improper disposal, accumulation in water bodies, low recycling rates and temporal action that causes physicochemical changes in plastics and the release of toxic products to animal health and nature. Some microorganisms may play crucial roles in improving plastic waste management in the future. Cunningamella echinulata has been identified as a promising candidate that remains viable for long periods and produces a cutinase that is capable of degrading plastic. Other recent approaches involving the use of microorganisms are discussed in this review. However, there does not seem to be a single science that is efficient or most appropriate for solving the problem of plastic pollution on the planet at present. Regulations, especially the implementation of different laws that address the entire plastic cycle in different countries, such as Brazil, the USA, China and the European Union, play important roles in the management of this waste and can contribute to reducing this problem. In the context of the transversality of the information compiled here, the current limitations are discussed, and an effective plan is proposed to reduce plastic pollution. Although it is challenging, it involves implementing legislation, promoting sustainable alternatives, improving collection and recycling systems, encouraging reuse, supporting research and technological innovation, promoting corporate responsibility, collaborating globally, raising public awareness, optimizing waste management and, above all, continuously monitoring the progress of actions based on measurable metrics.

Biofilm formation is a common mechanism by which bacteria undergo phenotypic changes to adapt to environmental stressors. The formation of biofilms has a detrimental impact in clinical settings by contributing to chronic infections and promoting antibiotic resistance. Delving into the molecular mechanisms, the quorum sensing (QS) system involves the release of chemical signals for bacterial cell-to-cell communication, which activates and regulates the expression of various genes and virulence factors, including those related to biofilm formation. Accordingly, the QS system becomes a potential target for combating biofilm-associated concerns. Natural products derived from plants have a long history of treating infectious diseases in humans due to their antimicrobial properties, making them valuable resources for screening anti-biofilm agents. This review aims to discover the mechanisms by which phytochemical agents inhibit QS, potentially offering promising new therapies for treating biofilm-associated infections. By targeting the QS system, these phytochemical agents can prevent bacterial aggregation and biofilm formation while also diminishing other bacterial virulence factors. Additionally, it is important to focus on the advancement of techniques and experiments to investigate their molecular mechanisms. A thorough understanding of these mechanisms may encourage further studies to evaluate the safety and efficacy of phytochemical agents used alone or in combination with other strategies.

Influenza A virus infection, commonly known as the flu, has persisted in the community for centuries. Although we have yearly vaccinations to prevent seasonal flu, there remains a dire need for antiviral drugs to treat active infections. The constantly evolving genome of the influenza A virus limits the number of effective antiviral therapeutic options. Over time, antiviral drugs become inefficient due to the development of resistance, as seen with adamantanes, which are now largely ineffective against most circulating strains of the virus. Neuraminidase inhibitors have long been the drug of choice, but due to selection pressure, strains are becoming resistant to this class of drugs. Baloxavir marboxil, a drug with a novel mode of action, can be used against strains resistant to other classes of drugs but is still not available in many countries. Deep research into nanoparticles has shown they are effective as antiviral drugs, opening a new avenue of research to use them as antiviral agents with novel modes of action. As this deadly virus, which has killed millions of people in the past, continues to develop resistance, there is an urgent need for new therapeutic agents with novel modes of action to halt active infections in patients. This review article covers the available therapeutic antiviral drug options with different modes of action, their effectiveness, and resistance to various strains of influenza A virus.

Endogenous H₂S has been proposed to be a universal defense mechanism against different antibiotics. Here, we studied the role of H₂S transiently generated during ciprofloxacin (CF) treatment in M9 minimal medium with sulfate or produced by E. coli when fed with cystine. The cysM and mstA mutants did not produce H₂S, while gshA generated more H₂S in response to ciprofloxacin in cystine-free media. All mutants showed a reduced ability to maintain cysteine homeostasis under these conditions. We found no relationship between H₂S generation, cysteine concentration and sensitivity to ciprofloxacin. Excess cysteine, which occurred during E. coli growth in cystine-fed media, triggered continuous H₂S production, accelerated glutathione synthesis and cysteine export. This was accompanied by a twofold increase in ciprofloxacin tolerance in all strains except gshA, whose sensitivity increased 5–8-fold at high CF doses, indicating the importance of GSH in restoring the intracellular redox situation during growth in cystine-fed media.

Fumarate and nitrate reduction regulatory protein (Fnr)—a global transcriptional regulator—can directly or indirectly regulate many genes in different metabolic pathways at the top of the bacterial transcription regulation network. The present study explored the regulatory mechanism of Fnr-mediated nitrite degradation in Lactobacillus plantarum WU14 through gene transcription and expression analysis of oxygen sensing and nir operon expression regulation by Fnr. The interaction and the mechanism of transcriptional regulation between Fnr and GlnR were also examined under nitrite stress. After Fnr and GlnR purification by glutathione S-transferase tags, they were successfully expressed in Escherichia coli by constructing an expression vector. The results of electrophoresis mobility shift assay and qRT-PCR indicated that Fnr specifically bound to the PglnR and Pnir promoters and regulated the expression of nitrite reductase (Nir) and GlnR. After 6–12 h of culture, the expressions of fnr and nir under anaerobic conditions were higher than under aerobic conditions; the expression of these two genes increased with sodium nitrite (NaNO₂) addition during aerobic culture. Overall, the present study indicated that Fnr not only directly participated in the expression of Nir and GlnR but also indirectly regulated the expression of Nir through GlnR regulation.

Graphical Abstract