Microbiology and Molecular Biology Reviews最新文献

SUMMARYVesicular mechanisms of drug resistance are known to exist across prokaryotes and eukaryotes. Vesicles are sacs that form when a lipid bilayer 'bends' to engulf and isolate contents from the cytoplasm or extracellular environment. They have a wide range of functions, including vehicles of communication within and across cells, trafficking of protein intermediates to their rightful organellar destinations, and carriers of substrates destined for autophagy. This review will provide an in-depth understanding of vesicular mechanisms of apicomplexan parasites, Plasmodium and Toxoplasma (that respectively cause malaria and toxoplasmosis). It will integrate mechanistic and evolutionarily insights gained from these and other pathogenic eukaryotes to develop a new model for plasmodial resistance to artemisinins, a class of drugs that have been the backbone of modern campaigns to eliminate malaria worldwide. We also discuss extracellular vesicles that present major vesicular mechanisms of drug resistance in parasite protozoa (that apicomplexans are part of). Finally, we provide a broader context of clinical drug resistance mechanisms of Plasmodium, Toxoplasma, as well as Cryptosporidium and Babesia, that are prominent members of the phyla, causative agents of cryptosporidiosis and babesiosis and significant for human and animal health.

SUMMARYInfection has long been hypothesized as the cause of multiple sclerosis (MS), and recent evidence for Epstein-Barr virus (EBV) as the trigger of MS is clear and compelling. This clarity contrasts with yet uncertain viral mechanisms and their relation to MS neuroinflammation and demyelination. As long as this disparity persists, it will invigorate virologists, molecular biologists, immunologists, and clinicians to ascertain how EBV potentiates MS onset, and possibly the disease's chronic activity and progression. Such efforts should take advantage of the diverse body of basic and clinical research conducted over nearly two centuries since the first clinical descriptions of MS plaques. Defining the contribution of EBV to the complex and multifactorial pathology of MS will also require suitable experimental models and techniques. Such efforts will broaden our understanding of virus-driven neuroinflammation and specifically inform the development of EBV-targeted therapies for MS management and, ultimately, prevention.

SUMMARYPathogens must acquire essential nutrients to successfully colonize and proliferate in host tissue. Additionally, nutrients provide signals that condition pathogen deployment of factors that promote disease. A series of transcriptomics experiments over the last 20 years, primarily with Cryptococcus neoformans and to a lesser extent with Cryptococcus gattii, provide insights into the nutritional requirements for proliferation in host tissues. Notably, the identified functions include a number of transporters for key nutrients including sugars, amino acids, metals, and phosphate. Here, we first summarize the in vivo gene expression studies and then discuss the follow-up analyses that specifically test the relevance of the identified transporters for the ability of the pathogens to cause disease. The conclusion is that predictions based on transcriptional profiling of cryptococcal cells in infected tissue are well supported by subsequent investigations using targeted mutations. Overall, the combination of transcriptomic and genetic approaches provides substantial insights into the nutritional requirements that underpin proliferation in the host.

SUMMARYLipopolysaccharides (LPS) are an integral part of the outer membrane of Gram-negative bacteria and play essential structural and functional roles in maintaining membrane integrity as well as in stress response and virulence. LPS comprises a membrane-anchored lipid A group, a sugar-based core region, and an O-antigen formed by repeating oligosaccharide units. 3-Deoxy-D-manno-octulosonic acid-lipid A (Kdo₂-lipid A) is the minimum LPS component required for bacterial survival. While LPS modifications are not essential, they play multifaceted roles in stress response and host-pathogen interactions. Gram-negative bacteria encode several distinct LPS-modifying phosphoethanolamine transferases (PET) that add phosphoethanolamine (pEtN) to lipid A or the core region of LPS. The pet genes differ in their genomic locations, regulation mechanisms, and modification targets of the encoded enzyme, consistent with their various roles in different growth niches and under varied stress conditions. The discovery of mobile colistin resistance genes, which represent lipid A-modifying pet genes that are encoded on mobile elements and associated with resistance to the last-resort antibiotic colistin, has led to substantial interest in PETs and pEtN-modified LPS over the last decade. Here, we will review the current knowledge of the functional diversity of pEtN-based LPS modifications, including possible roles in niche-specific fitness advantages and resistance to host-produced antimicrobial peptides, and discuss how the genetic and structural diversities of PETs may impact their function. An improved understanding of the PET group will further enhance our comprehension of the stress response and virulence of Gram-negative bacteria and help contextualize host-pathogen interactions.

SUMMARYThe lipid homeostasis pathways of bacterial pathogens have been studied comprehensively for their biochemical functionality. However, new and refined technologies have supported the interrogation of bacterial lipid and fatty acid homeostasis mechanisms in more complex environments, such as mammalian host niches. In particular, emerging findings on the breadth and depth of host fatty acid uptake have demonstrated their importance beyond merely fatty acid utilization for membrane synthesis, as they can contribute to virulence factor regulation, pathogenesis, and group-based behaviors. Lipid homeostasis is also intertwined with other metabolic and physiological processes in the bacterial cells, which appear to be largely unique per species, but overarching themes can be derived. This review combines the latest biochemical and structural findings and places these in the context of bacterial pathogenesis, thereby shedding light on the far-reaching implications of lipid homeostasis on bacterial success.

SUMMARYCoccidioides immitis and Coccidioides posadasii are fungal pathogens that cause systemic mycoses and are prevalent in arid regions in the Americas. While C. immitis mainly occurs in California and Washington, C. posadasii is widely distributed across North and South America. Both species induce coccidioidomycosis (San Joaquin Valley fever or, more commonly, Valley fever), with reported cases surging in the United States, notably in California and Arizona. Moreover, cases in Argentina, Brazil, and Mexico are on the rise. Climate change and environmental alterations conducive to Coccidioides spp. proliferation have been recently explored. Diagnostic challenges contribute to delayed treatment initiation, compounded by limited therapeutic options. Although antifungal drugs are often effective treatments, some patients do not respond to current therapies, underscoring the urgent need for a vaccine, particularly for vulnerable populations over 60 years old relocating to endemic areas. Despite recent progress, gaps persist in the understanding of Coccidioides ecology, host immune responses, and vaccine development. This review synthesizes recent research advancements in Coccidioides ecology, genomics, and immune responses, emphasizing ongoing efforts to develop a human vaccine.

SUMMARYThe striatin-interacting phosphatase and kinase (STRIPAK) complex is involved in the regulation of many developmental processes in eukaryotic microorganisms and all animals, including humans. STRIPAK is a component of protein phosphatase 2A (PP2A), a highly conserved serine-threonine phosphatase composed of catalytic subunits (PP2Ac), a scaffolding subunit (PP2AA) and various substrate-directing B regulatory subunits. In particular, the B''' regulatory subunit called striatin has evoked major interest over the last 20 years. Studies in fungal systems have contributed substantially to our current knowledge about STRIPAK composition, assembly, and cellular localization, as well as its regulatory role in autophagy and the morphology of fungal development. STRIPAK represents a signaling hub with many kinases and thus integrates upstream and downstream information from many conserved eukaryotic signaling pathways. A profound understanding of STRIPAK's regulatory role in fungi opens the gateway to understanding the multifarious functions carried out by STRIPAK in higher eukaryotes, including its contribution to malignant cell growth.

SUMMARYUrinary tract infection (UTI) is one of the most common infections in otherwise healthy individuals. UTI is also common in healthcare settings where patients often require urinary catheters to alleviate urinary retention. The placement of a urinary catheter often leads to catheter-associated urinary tract infection (CAUTI) caused by a broad range of opportunistic pathogens, commonly referred to as ESKAPE (Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter) pathogens. Our understanding of CAUTI is complicated by the differences in pathogens, in initial microbial load, changes that occur due to the duration of catheterization, and the relationship between infection (colonization) and disease symptoms. To advance our understanding of CAUTI, we reviewed UTI and CAUTI caused by Pseudomonas aeruginosa which is unique in that it is not commonly found associated with human microbiomes. For this reason, the ability of P. aeruginosa to cause UTI and CAUTI requires the introduction of the bacteria to the bladder from catheterization. Once in the host, the virulence factors used by P. aeruginosa in these infections remain an area of ongoing research. In this review, we will discuss studies that focus on P. aeruginosa UTI and CAUTI to better understand the infection dynamics and outcome in clinical settings, virulence factors associated with P. aeruginosa isolated from the urinary tract, and animal studies to test which bacterial factors are required for this infection. Understanding how P. aeruginosa can cause UTI and CAUTI can provide an understanding of how these infections initiate and progress and may provide possible strategies to limit these infections.

SUMMARYHepatitis B virus (HBV) is an important human pathogen that chronically infects approximately 250 million people in the world, resulting in ~1 million deaths annually. This virus is a hepatotropic virus and can cause severe liver diseases including cirrhosis and hepatocellular carcinoma. The entry of HBV into hepatocytes is initiated by the interaction of its envelope proteins with its receptors. This is followed by the delivery of the viral nucleocapsid to the nucleus for the release of its genomic DNA and the transcription of viral RNAs. The assembly of the viral capsid particles may then take place in the nucleus or the cytoplasm and may involve cellular membranes. This is followed by the egress of the virus from infected cells. In recent years, significant research progresses had been made toward understanding the entry, the assembly, and the egress of HBV particles. In this review, we discuss the molecular pathways of these processes and compare them with those used by hepatitis delta virus and hepatitis C virus , two other hepatotropic viruses that are also enveloped. The understanding of these processes will help us to understand how HBV replicates and causes diseases, which will help to improve the treatments for HBV patients.