Microbiology and Molecular Biology Reviews最新文献

SUMMARYViral myocarditis, an inflammatory disease of the myocardium caused by viral infections, poses a significant global health concern, particularly in young adults and children. This condition often progresses to dilated cardiomyopathy and heart failure, underscoring the urgent need for a deeper understanding of its underlying mechanisms. Central to its pathogenesis is the disruption of protein quality control (PQC) system, which is essential for maintaining cardiac proteostasis under both physiological and pathological conditions. This system, comprising molecular chaperones, the ubiquitin-proteasome system, and autophagy pathways, collectively ensures cellular homeostasis. In viral myocarditis, viral replication and host immune responses impose substantial stress on cardiomyocytes, overwhelming the PQC mechanisms. Consequently, misfolded and aggregated proteins, as well as damaged organelles, accumulate, further aggravating myocardial injury. Notably, while PQC pathways play a critical role in limiting viral replication and protecting cardiomyocytes, viruses can subvert these systems to enhance their own replication and provoke maladaptive responses, thereby worsening cardiac injury. This review summarizes current knowledge on the complex interplay between PQC system and viral myocarditis, highlights key knowledge gaps, and discusses potential therapeutic strategies to preserve cardiac function and improve clinical outcomes.

SUMMARYHaemophilus ducreyi is a Gram-negative coccobacillus that forms a distinct lineage with Aggregatibacter pleuropneumoniae and Mannheimia haemolytica within the Pasteurellaceae. H. ducreyi causes chancroid, which is characterized by painful genital ulcers (GU) and inguinal lymphadenitis, and facilitates the transmission of HIV. Although once thought to be exclusively sexually transmitted, H. ducreyi is now recognized as a major cause of non-sexually transmitted cutaneous ulcers (CU) on the lower legs of children who live in yaws-endemic areas. Due to the impact of chancroid on global health, the lack of human specimens, and the need to understand H. ducreyi pathogenesis, in 1993, we developed a model in which healthy adult volunteers are infected on the skin overlying the deltoid with the GU strain 35000HP and its isogenic mutants. This review summarizes 31 years of clinical experience with inoculating 429 unique participants and the behavior of strain 35000HP in the model. We examine sex and host effects on the outcome of initial inoculations and the results of second challenges of 53 participants, which together indicate that there is differential host susceptibility to infection, and explore the immunological basis for this phenomenon. We describe the evaluation of candidate bacterial virulence determinants in disease as determined in 38 mutant vs. parent comparison trials and the identification of potential vaccine candidates, which may be needed to control CU. We provide aggregate information on adverse events so that others can replicate this model. This review should also serve as a template for the ethical development of additional human infection models.

SUMMARYBacterial pathogens must navigate complex host environments to thrive, replicate, and ultimately transmit to new hosts. Effective transmission is critical for pathogen propagation and often requires overcoming host defenses and exploiting environmental conditions. The mechanisms used by bacterial pathogens to cause disease have been studied for decades, and numerous virulence factors have been identified and characterized through the use of genetic tools and animal models. While insightful, these discoveries have only scratched the surface of our understanding of disease mechanisms. Even less well understood is how pathogens move from an infected host to colonize and establish infection in a new host. Pathogens can move between hosts via direct and indirect modes, relying on numerous routes, such as respiratory, fecal-oral, direct contact, vector-borne, and vertical transmission. Recent advances in animal models for the study of bacterial transmission have enabled a more accurate recapitulation of transmission between humans. This review summarizes the current knowledge of bacterial transmission factors and animal models of transmission, and how these tools are advancing our understanding of the transmission mechanisms used by bacterial pathogens.

SUMMARYPleomorphism in influenza viruses, characterized by diverse morphological forms ranging from spherical virions to elongated filaments, has been suggested to present significant implications for pathogenesis. This review examines the role of pleomorphism on the influenza virus life cycle, encompassing viral attachment and entry, replication, assembly, and budding, as well as transmission dynamics. It explores the determinants' underlying morphological variability in virions and their impact on viral fitness and host interactions. Insights into how pleomorphic forms of the virus influence disease severity and the efficacy of antivirals are discussed. Understanding the implications of pleomorphism in influenza virus pathogenesis is crucial for the development of effective disease prevention, control, and treatment strategies.

SUMMARYIn recent years, exhaustive efforts have been made to dissect the composition of gut-associated microbial communities and associated interactions with their human host, which are thought to play a crucial role in host development, physiology, and metabolic functions. Although such studies were initially focused on the description of the compositional shifts in the microbiota that occur between different health conditions, more recently, they have provided key insights into the functional and metabolic contributions of the gut microbiota to overall host physiology. In this context, an important metabolic activity of the human gut microbiota is believed to be represented by the synthesis of various vitamins that may elicit considerable benefits to human health. A growing body of scientific literature is now available relating to (predicted) bacterial vitamin biosynthetic abilities, with ever-growing information concerning the prevalence of these biosynthetic abilities among members of the human microbiota. This review is aimed at disentangling if and how cooperative trophic interactions of human microbiota members contribute to vitamin production, and if such, gut microbiota-mediated vitamin production varies according to different life stages. Moreover, it offers a brief exploration of how different diets may influence vitamin production by shaping the overall composition and metabolic activity of the human gut microbiota while also providing preliminary insights into potential correlations between human microbiota-associated vitamin production and the occurrence of human diseases and/or metabolic disorders.

SUMMARYEngineered microbes are being programmed using synthetic DNA for applications in soil to overcome global challenges related to climate change, energy, food security, and pollution. However, we cannot yet predict gene transfer processes in soil to assess the frequency of unintentional transfer of engineered DNA to environmental microbes when applying synthetic biology technologies at scale. This challenge exists because of the complex and heterogeneous characteristics of soils, which contribute to the fitness and transport of cells and the exchange of genetic material within communities. Here, we describe knowledge gaps about gene transfer across soil microbiomes. We propose strategies to improve our understanding of gene transfer across soil communities, highlight the need to benchmark the performance of biocontainment measures in situ, and discuss responsibly engaging community stakeholders. We highlight opportunities to address knowledge gaps, such as creating a set of soil standards for studying gene transfer across diverse soil types and measuring gene transfer host range across microbiomes using emerging technologies. By comparing gene transfer rates, host range, and persistence of engineered microbes across different soils, we posit that community-scale, environment-specific models can be built that anticipate biotechnology risks. Such studies will enable the design of safer biotechnologies that allow us to realize the benefits of synthetic biology and mitigate risks associated with the release of such technologies.

SUMMARYGut microbes provide benefits to some animals, but their distribution and effects across diverse hosts are still poorly described. There is accumulating evidence for host specificity (i.e., a pattern where different microbes tend to associate with distinct host lineages), but the causes and consequences of this pattern are unclear. Combining experimental tests in the laboratory with broad surveys in the wild is a promising approach to gaining a comprehensive and mechanistic understanding of host specificity prevalence, origin, and importance. Social bees represent an ideal testbed for this endeavor because they are phylogenetically and functionally diverse, with host-specific, stable, and tractable gut microbiota. Furthermore, the western honeybee (Apis mellifera) is an emerging experimental model system for studying microbiota-host interactions. In this review, we summarize data on the prevalence and strength of host specificity of the social bee gut microbiota (bumblebees, stingless bees, and honeybees), as well as the potential and proven ecological and molecular mechanisms that maintain host specificity. Overall, we found that host specificity in bees is relatively strong and likely results from several processes, including host filtering mediated by the immune system and priority effects. However, more research is needed across multiple social bee species to confirm these findings. To help future research, we summarize emerging hypotheses in the field and propose several experimental and comparative tests. Finally, we conclude this review by highlighting the need to understand how host specificity can influence host health.

SUMMARYThe human microbiome, including bacteria, fungi, archaea, and viruses, is intimately linked to both health and disease. The relationship between bacteria and disease has received much attention and intensive investigation, while that of the fungal microbiome, also known as mycobiome, has lagged far behind bacteria. There is growing evidence showing mycobiome dysbiosis in cancer patients, and certain cancer-specific fungi may contribute to cancer progression by interacting with both host and bacteria. It was also demonstrated that the role of fungi-derived products in cancer should also not be underestimated. Therefore, investigating how fungal pathogenesis contributes to the onset and spread of cancer would yield crucial information for cancer diagnosis, prevention, and anti-cancer therapy.

SUMMARYKlebsiella pneumoniae is a gram-negative species, whose isolates are found in the environment and as commensals in the human gastrointestinal tract. This bacterium is among the leading causes of a range of nosocomial and community-acquired infections, particularly in immunocompromised individuals, where it can give rise to pneumonia, urinary tract infections, septicemia, and liver abscesses. Treatment of K. pneumoniae infections is compromised by the emergence of isolates producing carbapenemase and extended-spectrum β-lactamase enzymes, making it a high priority for new therapeutic approaches including vaccination and immunoprophylaxis. One potential target for these strategies is the O-antigen polysaccharide component of lipopolysaccharides, which are important virulence determinants for K. pneumoniae. Consideration of immunotherapeutic opportunities requires a comprehensive and fundamental understanding of O-polysaccharide structures, distribution of particular O serotypes in clinical isolates, and the potential for antigenic diversification. The number of recognized K. pneumoniae O-polysaccharide antigens has varied over time, complicated by the observation that some examples share similar structural (and potentially antigenically cross-reactive) elements, and by the existence of genetic loci for which corresponding O-polysaccharide structures have yet to be determined. Here, we provide a comprehensive integration of the current carbohydrate structures and genetic information, together with a proposal for an updated classification system for K. pneumoniae O-antigens, that is being implemented in Kaptive for molecular serotyping. The accumulated insight into O-polysaccharide assembly pathways is used to describe the molecular basis for O-antigen diversity in K. pneumoniae.