Building permits—control of type IV pilus assembly by PilB and its cofactors DOI Creative Commons

Nathan Roberge,

Lori L. Burrows

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Many bacteria produce type IV pili (T4P), surfaced-exposed protein filaments that enable cells to interact with their environment and transition from planktonic surface-adapted states. T4P are dynamic, undergoing rapid cycles of filament extension retraction facilitated by a complex nanomachine powered cytoplasmic motor ATPases. Dedicated assembly motors drive the pilus fiber into extracellular space, but like any machine, this process is tightly organized. These coordinated various ligands binding partners, which control or optimize functional associations machinery before commit crucial first step building pilus. This review focuses on molecular mechanisms regulate function. We discuss secondary messenger-dependent transcriptional post-translational regulation acting both directly through effectors. also recent discoveries naturally occurring inhibitors as well alternative motor-dependent signaling pathways. Given important virulence factors for many bacterial pathogens, studying these regulatory systems will provide new insights T4P-dependent physiology efficient strategies disable them.

Language: Английский

Pilin antigenic variants impact gonococcal lifestyle and antibiotic tolerance by modulating interbacterial forces DOI Creative Commons
Isabelle Wielert, Sebastian Kraus,

Thorsten E. Volkmann

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3003022 - e3003022

Published: Jan. 30, 2025

Type 4 pili (T4P) are multifunctional filaments involved in adhesion, surface motility, biofilm formation, and horizontal gene transfer. These extracellular polymers surface-exposed and, therefore, act as antigens. The human pathogen Neisseria gonorrhoeae uses pilin antigenic variation to escape immune surveillance, yet it is unclear how impacts most other functions of T4P. Here, we addressed this question by replacing the major a laboratory strain with pilins from clinical isolates. We reveal that resulting strains vary substantially their attractive forces. Strongly interacting bacteria form microcolonies while weakly retain planktonic lifestyle. In mixed microcolonies, different variant segregate agreement differential strength adhesion hypothesis. By combining structural predictions laser tweezers experiments, show C-terminal region crucial for attraction. Lifestyle affects growth kinetics antibiotic tolerance. presence ceftriaxone or ciprofloxacin, killing indicate strongly increased tolerance aggregating strains. propose produces population containing variants optimized growth, colonization, survivability under external stress. Different environments select variants, ensuring survival reproduction whole.

Language: Английский

Citations

0
Combating Pathogenic Immune Evasion: Sialidase-Activated Thermally Delayed Fluorescence for Probing and Modulating Host–Pathogen Interactions DOI
Qian Liu, Qinghua Wang, Xiangchuan Meng

et al.

ACS Sensors, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Innate immunity represents the primary defense against invasive pathogens with phagocytosis playing a central role in host and mediating immune inflammatory responses. However, such as Clostridium perfringens have developed strategies to overcome phagocytic clearance. Developing molecular tools identify target key factors pathogenic evasion can deepen our understanding of host–pathogen interactions aid exploring novel therapeutic strategies. As enzyme sialylation process C. perfringens, virulence factor sialidase is potential for investigating evasion. Herein, "turn-on" thermally activated delayed fluorescent probe SA-HBT-PXZ highly selective sensitive sensor, enabling time-resolved fluorescence imaging live bacterial cells, tissue sections, even infected mice. Furthermore, successfully employed screen inhibitors based on prompt emissions. The identified lead compounds effectively inhibit activity sialidases from leading an increased level differentiation macrophages into M1 subtype. This, turn, enhances ultimately suppresses escape bacteria. Our study provides infections.

Language: Английский

Citations

0
Identification and characterization of Vibrio anguillarum (GA strain) isolated from Obscure Pufferfish Takifugu obscurus DOI
Wei Gao,

Wenji Huang,

Ling Shao

et al.

Journal of Aquatic Animal Health, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

ABSTRACT Objective Aquaculture has faced significant challenges due to the emergence of various pathogens affecting fish species. One such species, Obscure Pufferfish Takifugu obscurus, experienced high mortality rates an outbreak disease on a fishery farm in Shanghai. Methods The pathogen responsible for this was isolated and identified as Vibrio anguillarum (GA strain) using combination morphological, biochemical, whole-genome single-nucleotide polymorphism-based phylogenetic analyses. Pathogenicity tests confirmed that GA strain could cause healthy Pufferfish, inducing overt hemorrhagic symptoms. Histopathological analysis performed assess whether tissue damage had occurred. Whole-genome sequencing revealed possessed 235 virulence genes two drug resistance-related genes: cyclic AMP receptor protein (CRP) regulator secondary metabolites A (rsmA). Testing via PCR further presence 10 common genes. Results Antibiotic susceptibility testing showed highly sensitive antibiotics tetracycline, doxycycline, minocycline, compound sulfamethoxazole resistant cefradine, cefazolin, penicillin, vancomycin. Conclusions To best our knowledge, is first study report V. Pufferfish. isolate exhibited strong multidrug resistance. findings lay foundation control investigation epidemiological mechanisms anguillarum.

Language: Английский

Citations

0
A General Method to Screen Nanobodies for Cytochrome P450 Enzymes from a Yeast Surface Display Library DOI Creative Commons

Yudong Sun,

Cristian Martinez-Ramos,

Eugene Chen

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1863 - 1863

Published: Aug. 15, 2024

The availability of yeast surface display nanobody (Nb) libraries offers a convenient way to acquire antigen-specific nanobodies that may be useful for protein structure-function studies and/or therapeutic applications, complementary the conventional method acquiring through immunization in camelids. In this study, we developed general approach select cytochrome P450 enzymes from highly diverse library. We tested our on three including CYP102A1, neuronal nitric oxide synthase (nNOS), and complex CYP2B4:POR, using novel streamlined where biotinylated P450s were bound fluorescent-labeled streptavidin Nb screening. Nb-antigen binders selectively enriched magnetic-activated cell sorting (MACS) fluorescence-activated (FACS). After two rounds MACS, population positive was by >5-fold compared naïve subsequent FACS selection, with gating 0.1%, identified 634, 270, 215 nNOS, respectively. CYP102A1 further triaged based EC

Language: Английский

Citations

0
Building permits—control of type IV pilus assembly by PilB and its cofactors DOI Creative Commons

Nathan Roberge,

Lori L. Burrows

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Many bacteria produce type IV pili (T4P), surfaced-exposed protein filaments that enable cells to interact with their environment and transition from planktonic surface-adapted states. T4P are dynamic, undergoing rapid cycles of filament extension retraction facilitated by a complex nanomachine powered cytoplasmic motor ATPases. Dedicated assembly motors drive the pilus fiber into extracellular space, but like any machine, this process is tightly organized. These coordinated various ligands binding partners, which control or optimize functional associations machinery before commit crucial first step building pilus. This review focuses on molecular mechanisms regulate function. We discuss secondary messenger-dependent transcriptional post-translational regulation acting both directly through effectors. also recent discoveries naturally occurring inhibitors as well alternative motor-dependent signaling pathways. Given important virulence factors for many bacterial pathogens, studying these regulatory systems will provide new insights T4P-dependent physiology efficient strategies disable them.

Language: Английский

Citations

0