Current opinion in microbiology最新文献

CRISPR-based gene drive (GD) systems bias allele inheritance during meiosis, enabling transgenes to spread at rates exceeding Mendel's law of segregation. This capability underlies their potential as powerful tools for controlling mosquito-borne diseases. GDs can be engineered either to suppress mosquito populations or to modify them by introducing traits that block pathogen transmission. Recent advances have focused on improving evolutionary stability, with modeling studies providing insights into expected population dynamics. With a focus on the most current population modification GDs, we discuss advances in GD architectures - including integral and allelic drives, combined modification-suppression systems, and both homing and non-homing toxin-antidote designs - that expand the range of possible strategies and address limitations of early homing drives. Numerous antipathogen effectors with strong pathogen-blocking activity can now be coupled to these systems, with current efforts assessing their durability against genetically diverse pathogens. Key challenges remain, including resistance evolution, ecological impacts, and long-term stability. Nonetheless, GDs offer a promising approach for reducing disease transmission, especially in regions where conventional interventions are difficult to sustain.

Superficial dermatophyte infections are a common cause of fungal diseases worldwide. These filamentous fungi specialize in degrading keratinized tissues (skin, hair, nails) and show an evolutionary trajectory from zoophilic species to anthropophilic species. In recent years, major human pathogens have emerged from the Trichophyton genus, such as T. indotineae, causing outbreaks of chronic, extensive, and difficult-to-treat dermatophytoses. Herein, we discuss recent findings on host-dermatophyte interactions with a focus on Trichophyton. Since the establishment of infection models that have helped to uncover virulence factors in adhesion, germination, and tissue invasion, new research highlights the role of the transcriptional factor StuA and the serine protease subtilisin 6 in dermatophyte pathogenesis. We also emphasize dermatophyte immunity, as clinicians increasingly encounter patients with chronic infections or, in rare instances, patients with deep and disseminated infections. Although keratinocytes mediate early host defense mechanisms, it is apparent that T-cells, specifically T-helper (Th) cells 1 and 17, are required for controlling dermatophytosis. This protective response is characterized by IFN-γ and IL-17, as well as a delayed-type skin hypersensitivity reaction. By contrast, a skewed Th2-type response - marked by IL-4, IgE, and dermatophyte-specific IgG - is often associated with a worsened clinical prognosis, including the development of chronicity and exacerbation of atopic conditions. Through genomic sequencing, CARD9 was identified as a key signaling molecule in dermatophyte immunity and is linked to the development of deep dermatophytosis, possibly leading to extracutaneous disseminations. Further research efforts are warranted to decipher these complex interactions and to develop new treatment strategies.

The phagosome is a dynamic organelle whose function is defined by engulfment and elimination of particles, including debris, dead cells, and foreign material such as invading pathogens. To effectively contain, kill, and degrade pathogens, the phagosome undergoes highly coordinated maturation through interaction with proteins, second messengers, and other organelles in the endocytic pathway. This process involves a progressive decrease in luminal pH as the phagosome fuses with other endocytic vesicles and lysosomes. While diverse pathogens may trigger different mechanisms of phagosome maturation or interfere with these processes, this review focuses on host processes that lead to the successful maturation of macrophage phagosomes containing fungal pathogens (hereafter referred to as fungal phagosomes). Fungal pathogens are unique in that they are comparatively very large infectious particles and can undergo rapid growth within the phagosome. However, phagosome maturation maintains phagosomal membrane integrity, allowing phagocytes to hinder fungal growth and exert microbicidal activity within this hostile compartment. Recent findings suggest that phagosome maturation depends on interaction with other organelles, such as the endoplasmic reticulum. Additionally, roles for mitochondria are also emerging for the regulation of fungicidal activity within the phagosome. As these processes are crucial for successful host defense during fungal pathogen infection, modulation fungal phagosome maturation and function is a promising direction for host-directed therapeutics to treat fungal infection.

Engineering bacteria to address human health challenges has been an active and productive area of research for many decades. Historically, a major emphasis of this work has been on modifying laboratory-adapted species to generate chemical or biological compounds for therapeutic use or for further study. In recent years, however, there has been a growing interest in utilizing nonmodel commensal and probiotic bacterial strains for development as in situ engineered living therapeutic or diagnostic machines. While substantial insight can be gained from previous work in well-studied organisms such as Escherichia coli, effective genetic and metabolic manipulation of novel species often requires novel tools. Here, we highlight strategies for the development of synthetic biology toolboxes for nonmodel bacterial strains to assist researchers across disciplines in establishing the molecular biology framework required to work with relatively understudied species. We focus on advances in engineering the Bacteroides genus as an example of how to establish such a pipeline.