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Microbes and Infection 2023Bordetella pertussis still circulates worldwide despite vaccination. Fimbriae are components of some acellular pertussis vaccines. Population fluctuations of...
INTRODUCTION
Bordetella pertussis still circulates worldwide despite vaccination. Fimbriae are components of some acellular pertussis vaccines. Population fluctuations of B. pertussis fimbrial serotypes (FIM2 and FIM3) are observed, and fim3 alleles (fim3-1 [clade 1] and fim3-2 [clade 2]) mark a major phylogenetic subdivision of B. pertussis.
OBJECTIVES
To compare microbiological characteristics and expressed protein profiles between fimbrial serotypes FIM2 and FIM3 and genomic clades.
METHODS
A total of 19 isolates were selected. Absolute protein abundance of the main virulence factors, autoagglutination and biofilm formation, bacterial survival in whole blood, induced blood cell cytokine secretion, and global proteome profiles were assessed.
RESULTS
Compared to FIM3, FIM2 isolates produced more fimbriae, less cellular pertussis toxin subunit 1 and more biofilm, but auto-agglutinated less. FIM2 isolates had a lower survival rate in cord blood, but induced higher levels of IL-4, IL-8 and IL-1β secretion. Global proteome comparisons uncovered 15 differentially produced proteins between FIM2 and FIM3 isolates, involved in adhesion and metabolism of metals. FIM3 isolates of clade 2 produced more FIM3 and more biofilm compared to clade 1.
CONCLUSION
FIM serotype and fim3 clades are associated with proteomic and other biological differences, which may have implications on pathogenesis and epidemiological emergence.
Topics: Humans; Bordetella pertussis; Whooping Cough; Serogroup; Fimbriae Proteins; Phylogeny; Proteome; Proteomics; Virulence Factors, Bordetella; Pertussis Vaccine; Fimbriae, Bacterial
PubMed: 37245862
DOI: 10.1016/j.micinf.2023.105152 -
Nature Reviews. Microbiology Jul 2019The surfaces of many bacteria are decorated with long, exquisitely thin appendages called type IV pili (T4P), dynamic filaments that are rapidly polymerized and... (Review)
Review
The surfaces of many bacteria are decorated with long, exquisitely thin appendages called type IV pili (T4P), dynamic filaments that are rapidly polymerized and depolymerized from a pool of pilin subunits. Cycles of pilus extension, binding and retraction enable T4P to perform a phenomenally diverse array of functions, including twitching motility, DNA uptake and microcolony formation. On the basis of recent developments, a comprehensive understanding is emerging of the molecular architecture of the T4P machinery and the filament it builds, providing mechanistic insights into the assembly and retraction processes. Combined microbiological and biophysical approaches have revealed how T4P dynamics influence self-organization of bacteria, how bacteria respond to external stimuli to regulate T4P activity for directed movement, and the role of T4P retraction in surface sensing. In this Review, we discuss the T4P machine architecture and filament structure and present current molecular models for T4P dynamics, with a particular focus on recent insights into T4P retraction. We also discuss the functional consequences of T4P dynamics, which have important implications for bacterial lifestyle and pathogenesis.
Topics: Bacterial Physiological Phenomena; Biophysical Phenomena; Fimbriae Proteins; Fimbriae, Bacterial; Kinetics; Models, Biological; Type IV Secretion Systems
PubMed: 30988511
DOI: 10.1038/s41579-019-0195-4 -
Nature Reviews. Microbiology Oct 2018The formation of multicellular microbial communities, called biofilms, starts from the adhesion of a few planktonic cells to the surface. The transition from a... (Review)
Review
The formation of multicellular microbial communities, called biofilms, starts from the adhesion of a few planktonic cells to the surface. The transition from a free-living planktonic lifestyle to a sessile, attached state is a multifactorial process that is determined by biological, chemical and physical properties of the environment, the surface and the bacterial cell. The initial weak, reversible interactions between a bacterium and a surface strengthen to yield irreversible adhesion. In this Review, we summarize our understanding of the mechanisms governing bacterial adhesion at the single-cell level, including the physical forces experienced by a cell before reaching the surface, the first contact with a surface and the transition from reversible to permanent adhesion.
Topics: Bacteria; Bacterial Adhesion; Biofilms; Fimbriae, Bacterial; Surface Properties
PubMed: 30008468
DOI: 10.1038/s41579-018-0057-5 -
EcoSal Plus Mar 2019The chaperone-usher (CU) pathway is a conserved secretion system dedicated to the assembly of a superfamily of virulence-associated surface structures by a wide range of... (Review)
Review
The chaperone-usher (CU) pathway is a conserved secretion system dedicated to the assembly of a superfamily of virulence-associated surface structures by a wide range of Gram-negative bacteria. Pilus biogenesis by the CU pathway requires two specialized assembly components: a dedicated periplasmic chaperone and an integral outer membrane assembly and secretion platform termed the usher. The CU pathway assembles a variety of surface fibers, ranging from thin, flexible filaments to rigid, rod-like organelles. Pili typically act as adhesins and function as virulence factors that mediate contact with host cells and colonization of host tissues. Pilus-mediated adhesion is critical for early stages of infection, allowing bacteria to establish a foothold within the host. Pili are also involved in modulation of host cell signaling pathways, bacterial invasion into host cells, and biofilm formation. Pili are critical for initiating and sustaining infection and thus represent attractive targets for the development of antivirulence therapeutics. Such therapeutics offer a promising alternative to broad-spectrum antibiotics and provide a means to combat antibiotic resistance and treat infection while preserving the beneficial microbiota. A number of strategies have been taken to develop antipilus therapeutics, including vaccines against pilus proteins, competitive inhibitors of pilus-mediated adhesion, and small molecules that disrupt pilus biogenesis. Here we provide an overview of the function and assembly of CU pili and describe current efforts aimed at interfering with these critical virulence structures.
Topics: Adhesins, Bacterial; Bacterial Secretion Systems; Clinical Trials as Topic; Escherichia coli Proteins; Fimbriae Proteins; Fimbriae, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Models, Molecular; Molecular Chaperones; Uropathogenic Escherichia coli; Virulence
PubMed: 30873935
DOI: 10.1128/ecosalplus.ESP-0033-2018 -
Current Opinion in Microbiology Apr 2018The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside... (Review)
Review
The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside from the well-described subtype T4aP of the Gram-negative genera, including Myxococcus, Pseudomonas and Neisseria, the Tad (tight adherence) pilus secretion system re-shuffles homologous parts from other secretion systems along with uncharacterized components into a new type of protein translocation apparatus. A representative of the Tad apparatus, the Caulobacter crescentus pilus assembly (Cpa) machine is built exclusively at the newborn cell pole once per cell cycle. Recent comprehensive genetic analyses unearthed a myriad of spatiotemporal determinants acting on the Tad/Cpa system, many of which are conserved in other α-proteobacteria, including obligate intracellular pathogens and symbionts.
Topics: Bacterial Adhesion; Bacterial Proteins; Caulobacter; Fimbriae, Bacterial; Gene Expression Regulation, Bacterial; Models, Molecular; Pseudomonas aeruginosa
PubMed: 29161615
DOI: 10.1016/j.mib.2017.10.017 -
Nature Reviews. Microbiology May 2017Pili are crucial virulence factors for many Gram-negative pathogens. These surface structures provide bacteria with a link to their external environments by enabling... (Review)
Review
Pili are crucial virulence factors for many Gram-negative pathogens. These surface structures provide bacteria with a link to their external environments by enabling them to interact with, and attach to, host cells, other surfaces or each other, or by providing a conduit for secretion. Recent high-resolution structures of pilus filaments and the machineries that produce them, namely chaperone-usher pili, type IV pili, conjugative type IV secretion pili and type V pili, are beginning to explain some of the intriguing biological properties that pili exhibit, such as the ability of chaperone-usher pili and type IV pili to stretch in response to external forces. By contrast, conjugative pili provide a conduit for the exchange of genetic information, and recent high-resolution structures have revealed an integral association between the pilin subunit and a phospholipid molecule, which may facilitate DNA transport. In addition, progress in the area of cryo-electron tomography has provided a glimpse of the overall architecture of the type IV pilus machinery. In this Review, we examine recent advances in our structural understanding of various Gram-negative pilus systems and discuss their functional implications.
Topics: Bacterial Adhesion; Conjugation, Genetic; Fimbriae Proteins; Fimbriae, Bacterial; Gram-Negative Bacteria; Virulence Factors
PubMed: 28496159
DOI: 10.1038/nrmicro.2017.40 -
Current Opinion in Microbiology Apr 2016Type IV pili, a special class of bacterial surface filaments, are key behavioral mediators for many important human pathogens. However, we know very little about the... (Review)
Review
Type IV pili, a special class of bacterial surface filaments, are key behavioral mediators for many important human pathogens. However, we know very little about the role of these structures in the lifestyles of plant-associated bacteria. Over the past few years, several groups studying the extensive genus of Xanthomonas spp. have gained insights into the roles of played by type IV pili in bacteria-host interactions and pathogenesis, motility, biofilm formation, and interactions with bacteriophages. Protein-protein interaction studies have identified T4P regulators and these, along with structural studies, have begun to reveal some of the possible molecular mechanisms that may control the extension/retraction cycles of these dynamic filaments.
Topics: Bacterial Proteins; Fimbriae, Bacterial; Gene Expression Regulation, Bacterial; Xanthomonas
PubMed: 26874963
DOI: 10.1016/j.mib.2016.01.007 -
Current Issues in Molecular Biology 2019(Spn) and (Spy) cause many invasive and noninvasive diseases responsible for high morbidity and mortality worldwide. Safe, efficacious and affordable vaccines could... (Review)
Review
(Spn) and (Spy) cause many invasive and noninvasive diseases responsible for high morbidity and mortality worldwide. Safe, efficacious and affordable vaccines could have a significant, positive impact on the global infectious disease burden. Since the implementation of pneumococcal vaccine in the 1980s, the incidence of Spn infection has decreased significantly. Still so, these currently used multivalent polysaccharides and conjugated pneumococcal vaccines have some limitations. For Spy, there are even no vaccines available yet. There is an urgent need of new vaccines against Spn and Spy. Encouragingly, with the hard work of many investigators worldwide, a number of new vaccines candidates are developed with promising results. Of them, many have already entered the clinical trial stage. This review will describe the current status of Spn and Spy vaccine development, with particular focus on protein-based strategy.
Topics: Bacterial Proteins; Clinical Trials as Topic; Cytotoxins; Fimbriae, Bacterial; Gene Expression; Humans; Immunogenicity, Vaccine; Polysaccharides, Bacterial; Serogroup; Streptococcal Infections; Streptococcal Vaccines; Streptococcus pneumoniae; Vaccines, Attenuated; Vaccines, Conjugate; Vaccines, Subunit; Virulence
PubMed: 31166182
DOI: 10.21775/cimb.032.645 -
Molecular Microbiology Mar 2021The type II secretion system (T2SS) is a multi-protein complex used by many bacteria to move substrates across their cell membrane. Substrates released into the... (Review)
Review
The type II secretion system (T2SS) is a multi-protein complex used by many bacteria to move substrates across their cell membrane. Substrates released into the environment serve as local and long-range effectors that promote nutrient acquisition, biofilm formation, and pathogenicity. In both animals and plants, the T2SS is increasingly recognized as a key driver of virulence. The T2SS spans the bacterial cell envelope and extrudes substrates through an outer membrane secretin channel using a pseudopilus. An inner membrane assembly platform and a cytoplasmic motor controls pseudopilus assembly. This microreview focuses on the structure and mechanism of the T2SS. Advances in cryo-electron microscopy are enabling increasingly elaborate sub-complexes to be resolved. However, key questions remain regarding the mechanism of pseudopilus extension and retraction, and how this is coupled with the choreography of the substrate moving through the secretion system. The T2SS is part of an ancient type IV filament superfamily that may have been present within the last universal common ancestor (LUCA). Overall, mechanistic principles that underlie T2SS function have implication for other closely related systems such as the type IV and tight adherence pilus systems.
Topics: Amino Acid Sequence; Animals; Bacterial Outer Membrane Proteins; Bacterial Physiological Phenomena; Bacterial Proteins; Cryoelectron Microscopy; Fimbriae, Bacterial; Humans; Models, Molecular; Protein Conformation; Secretin; Type II Secretion Systems; Virulence Factors
PubMed: 33283907
DOI: 10.1111/mmi.14664 -
Biochimica Et Biophysica Acta Sep 2014Uropathogenic Escherichia coli (UPEC) cause urinary tract infections (UTIs) in approximately 50% of women. These bacteria use type 1 and P pili for host recognition and... (Review)
Review
BACKGROUND
Uropathogenic Escherichia coli (UPEC) cause urinary tract infections (UTIs) in approximately 50% of women. These bacteria use type 1 and P pili for host recognition and attachment. These pili are assembled by the chaperone-usher pathway of pilus biogenesis.
SCOPE OF REVIEW
The review examines the biogenesis and adhesion of the UPEC type 1 and P pili. Particular emphasis is drawn to the role of the outer membrane usher protein. The structural properties of the complete pilus are also examined to highlight the strength and functionality of the final assembly.
MAJOR CONCLUSIONS
The usher orchestrates the sequential addition of pilus subunits in a defined order. This process follows a subunit-incorporation cycle which consists of four steps: recruitment at the usher N-terminal domain, donor-strand exchange with the previously assembled subunit, transfer to the usher C-terminal domains and translocation of the nascent pilus. Adhesion by the type 1 and P pili is strengthened by the quaternary structure of their rod sections. The rod is endowed with spring-like properties which provide mechanical resistance against urine flow. The distal adhesins operate differently from one another, targeting receptors in a specific manner. The biogenesis and adhesion of type 1 and P pili are being therapeutically targeted, and efforts to prevent pilus growth or adherence are described.
GENERAL SIGNIFICANCE
The combination of structural and biochemical study has led to the detailed mechanistic understanding of this membrane spanning nano-machine. This can now be exploited to design novel drugs able to inhibit virulence. This is vital in the present era of resurgent antibiotic resistance. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.
Topics: Bacterial Adhesion; Escherichia coli Infections; Female; Fimbriae, Bacterial; Humans; Male; Urinary Tract Infections; Uropathogenic Escherichia coli
PubMed: 24797039
DOI: 10.1016/j.bbagen.2014.04.021