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International Journal of Medical... Oct 2020Pneumococci are a common cause of severe infections, such as otitis media, pneumonia, meningitis and bacteremia. Pili are detected in a small proportion of pneumococcal... (Review)
Review
Pneumococci are a common cause of severe infections, such as otitis media, pneumonia, meningitis and bacteremia. Pili are detected in a small proportion of pneumococcal population, but these structures have recently been associated with bacterial virulence in humans. Therefore, the epidemiological relationships between pneumococcal pili, serotype and antimicrobial resistance are of interest. This study aims to discuss the virulence contribution of the Streptococcus pneumoniae pili and the epidemiological relationships among the pilus genes, antimicrobial resistance trends, regional serotypes and genotypic variations. Previous reports have characterized the pneumococcal pilus islet as a clonal feature in the pneumococcal serotypes that are covered by the pneumococcal conjugate vaccine (PCV), including serotypes 19A, 19F, 23F and 7F. Many of the pneumococcal molecular epidemiology network (PMEN) clones are piliated isolates that are also strongly associated with a high frequency of multidrug resistance. Most of these piliated pneumococcal isolates belong to a few clonal complexes (CC), such as CC320, CC199, CC271, CC191 and CC156. Additional molecular epidemiology and genomic studies, particularly whole genome sequence analysis (WGS), are needed to develop an in-depth understanding of the piliated pneumococcal isolates.
Topics: Anti-Bacterial Agents; Fimbriae, Bacterial; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Serotyping; Streptococcus pneumoniae
PubMed: 33092697
DOI: 10.1016/j.ijmm.2020.151449 -
Structure (London, England : 1993) Dec 2021Type IV pili (T4P) are distinctive dynamic filaments at the surface of many bacteria that can rapidly extend and retract and withstand strong forces. T4P are important...
Type IV pili (T4P) are distinctive dynamic filaments at the surface of many bacteria that can rapidly extend and retract and withstand strong forces. T4P are important virulence factors in many human pathogens, including Enterohemorrhagic Escherichia coli (EHEC). The structure of the EHEC T4P has been determined by integrating nuclear magnetic resonance (NMR) and cryo-electron microscopy data. To better understand pilus assembly, stability, and function, we performed a total of 108 ms all-atom molecular dynamics simulations of wild-type and mutant T4P. Extensive characterization of the conformational landscape of T4P in different conditions of temperature, pH, and ionic strength is complemented with targeted mutagenesis and biochemical analyses. Our simulations and NMR experiments reveal a conserved set of residues defining a calcium-binding site at the interface between three pilin subunits. Calcium binding enhances T4P stability ex vivo and in vitro, supporting the role of this binding site as a potential pocket for drug design.
Topics: Binding Sites; Cryoelectron Microscopy; Enterohemorrhagic Escherichia coli; Fimbriae Proteins; Fimbriae, Bacterial; Molecular Dynamics Simulation
PubMed: 34520738
DOI: 10.1016/j.str.2021.07.008 -
Current Opinion in Microbiology Jun 2024Bacteria utilize type IV pili (T4P) to interact with their environment, where they facilitate processes including motility, adherence, and DNA uptake. T4P require... (Review)
Review
Bacteria utilize type IV pili (T4P) to interact with their environment, where they facilitate processes including motility, adherence, and DNA uptake. T4P require multisubunit, membrane-spanning nanomachines for assembly. The tight adherence (Tad) pili are an Archaea-derived T4P subgroup whose machinery exhibits significant mechanistic and architectural differences from bacterial type IVa and IVb pili. Most Tad biosynthetic genes are encoded in a single locus that is widespread in bacteria due to facile acquisition via horizontal gene transfer. These loci experience extensive structural rearrangements, including the acquisition of novel regulatory or biosynthetic genes, which fine-tune their function. This has permitted their integration into many different bacterial lifestyles, including the Caulobacter crescentus cell cycle, Myxococcus xanthus predation, and numerous plant and mammalian pathogens and symbionts.
Topics: Fimbriae, Bacterial; Caulobacter crescentus; Bacteria; Bacterial Adhesion; Gene Transfer, Horizontal; Fimbriae Proteins; Bacterial Proteins; Myxococcus xanthus
PubMed: 38579360
DOI: 10.1016/j.mib.2024.102468 -
IUBMB Life Jul 2015Pilins or fimbrilins are a class of proteins found in bacterial surface pilus, a hair-like surface appendage. Both the Gram-negative and -positive bacteria produce... (Review)
Review
Pilins or fimbrilins are a class of proteins found in bacterial surface pilus, a hair-like surface appendage. Both the Gram-negative and -positive bacteria produce pilins to assemble pili on their cell-surface for different purposes including adherence, twitching motility, conjugation, immunomodulation, biofilm formation, and electron transfer. Immunogenic properties of the pilins make them attractive vaccine candidates. The polymerized pilins play a key role in the initiation of host adhesion, which is a critical step for bacterial colonization and infection. Because of their key role in adhesion and exposure on the cell surface, targeting the pilins-mediated adhesion (anti-adhesion therapy) is also seen as a promising alternative approach for preventing and treating bacterial infections, one that may overcome their ever-increasing repertoires of resistance mechanisms. Individual pilins interact with each other non-covalently to assemble the pilus fiber with the help of associated proteins like chaperones and Usher in Gram-negative bacteria. In contrast, the pilins in Gram-positive bacteria often connect with each other covalently, with the help of sortases. Certain unique structural features present on the pilins distinguish them from one another across different bacterial strains, and these dictate their cellular targets and functions. While the structure of pilins has been extensively studied in Gram-negative pathogenic bacteria, the pilins in Gram-positive pathogenic bacteria have been in only during the last decade. Recently, the discovery of pilins in non-pathogenic bacteria, such as Lactobacillus rhamnosus GG, has received great attention, though traditionally the attention was on pathogenic bacteria. This review summarizes and discusses the current structural knowledge of pilins in Gram-positive bacteria with emphasis on those pilins which are sortase substrates.
Topics: Amino Acid Motifs; Amino Acid Sequence; Conserved Sequence; Fimbriae Proteins; Fimbriae, Bacterial; Gram-Positive Bacteria; Protein Structure, Tertiary
PubMed: 26178080
DOI: 10.1002/iub.1400 -
Proceedings of the National Academy of... Dec 2023Type IV pili (T4P) are ubiquitous in both bacteria and archaea. They are polymers of the major pilin protein, which has an extended and protruding N-terminal helix, α1,...
Type IV pili (T4P) are ubiquitous in both bacteria and archaea. They are polymers of the major pilin protein, which has an extended and protruding N-terminal helix, α1, and a globular C-terminal domain. Cryo-EM structures have revealed key differences between the bacterial and archaeal T4P in their C-terminal domain structure and in the packing and continuity of α1. This segment forms a continuous α-helix in archaeal T4P but is partially melted in all published bacterial T4P structures due to a conserved helix breaking proline at position 22. The tad (tight adhesion) T4P are found in both bacteria and archaea and are thought to have been acquired by bacteria through horizontal transfer from archaea. Tad pilins are unique among the T4 pilins, being only 40 to 60 residues in length and entirely lacking a C-terminal domain. They also lack the Pro22 found in all high-resolution bacterial T4P structures. We show using cryo-EM that the bacterial tad pilus from is composed of continuous helical subunits that, like the archaeal pilins, lack the melted portion seen in other bacterial T4P and share the packing arrangement of the archaeal T4P. We further show that a bacterial T4P, the toxin coregulated pilus, which lacks Pro22 but is not in the tad family, has a continuous N-terminal α-helix, yet its α1 s are arranged similar to those in other bacterial T4P. Our results highlight the role of Pro22 in helix melting and support an evolutionary relationship between tad and archaeal T4P.
Topics: Fimbriae Proteins; Fimbriae, Bacterial; Archaea; Bacteria
PubMed: 38011558
DOI: 10.1073/pnas.2316668120 -
Trends in Microbiology Dec 2015The bacterial type IV pilus (T4P) is a versatile molecular machine with a broad range of functions. Recent advances revealed that the molecular components and the... (Review)
Review
The bacterial type IV pilus (T4P) is a versatile molecular machine with a broad range of functions. Recent advances revealed that the molecular components and the biophysical properties of the machine are well conserved among phylogenetically distant bacterial species. However, its functions are diverse, and include adhesion, motility, and horizontal gene transfer. This review focusses on the role of T4P in surface motility and bacterial interactions. Different species have evolved distinct mechanisms for intracellular coordination of multiple pili and of pili with other motility machines, ranging from physical coordination to biochemical clocks. Coordinated behavior between multiple bacteria on a surface is achieved by active manipulation of surfaces and modulation of pilus-pilus interactions. An emerging picture is that the T4P actively senses and responds to environmental conditions.
Topics: Bacteria; Bacterial Adhesion; Bacterial Physiological Phenomena; Biomechanical Phenomena; Elasticity; Evolution, Molecular; Fimbriae Proteins; Fimbriae, Bacterial; Locomotion; Models, Molecular; Mutation; Pseudomonas aeruginosa
PubMed: 26497940
DOI: 10.1016/j.tim.2015.09.002 -
Future Microbiology Apr 2022The emergence of as a potential threat in persistent infections can be attributed to the plethora of virulence factors expressed by it. This review discusses the... (Review)
Review
The emergence of as a potential threat in persistent infections can be attributed to the plethora of virulence factors expressed by it. This review discusses the various virulence factors that help this pathogen to establish an infection and regulatory systems controlling these virulence factors. Cell-associated virulence factors such as flagella, type IV pili and non-pilus adhesins have been reviewed. Extracellular virulence factors have also been explained. Quorum-sensing systems present in play a cardinal role in regulating the expression of virulence factors. The identification of novel virulence factors in hypervirulent strains indicate that the expression of virulence is dynamic and constantly evolving. An understanding of this is critical for the better clinical management of infections.
Topics: Fimbriae, Bacterial; Pseudomonas aeruginosa; Quorum Sensing; Virulence; Virulence Factors
PubMed: 35289684
DOI: 10.2217/fmb-2021-0158 -
EcoSal Plus Feb 2019The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface... (Review)
Review
The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface or extracellular space of Gram-negative bacteria. Its contribution to survival of both extracellular and intracellular pathogens as well as environmental species of proteobacteria is evident. This dynamic, multicomponent machinery spans the entire cell envelope and consists of a cytoplasmic ATPase, several inner membrane proteins, a periplasmic pseudopilus, and a secretin pore embedded in the outer membrane. Despite the -envelope configuration of the T2S nanomachine, proteins to be secreted engage with the system first once they enter the periplasmic compartment via the Sec or TAT export system. Thus, the T2SS is specifically dedicated to their outer membrane translocation. The many sequence and structural similarities between the T2SS and type IV pili suggest a common origin and argue for a pilus-mediated mechanism of secretion. This minireview describes the structures, functions, and interactions of the individual T2SS components and the general architecture of the assembled T2SS machinery and briefly summarizes the transport and function of a growing list of T2SS exoproteins. Recent advances in cryo-electron microscopy, which have led to an increased understanding of the structure-function relationship of the secretin channel and the pseudopilus, are emphasized.
Topics: Adenosine Triphosphatases; Bacterial Proteins; Cryoelectron Microscopy; Fimbriae, Bacterial; Gram-Negative Bacteria; Membrane Proteins; Models, Molecular; Periplasm; Protein Binding; Secretin; Type II Secretion Systems
PubMed: 30767847
DOI: 10.1128/ecosalplus.ESP-0034-2018 -
Proceedings of the National Academy of... Jul 2022Despite an extensive theoretical and numerical background, the translocation ratchet mechanism, which is fundamental for the transmembrane transport of biomolecules, has...
Despite an extensive theoretical and numerical background, the translocation ratchet mechanism, which is fundamental for the transmembrane transport of biomolecules, has never been experimentally reproduced at the nanoscale. Only the Sec61 and bacterial type IV pilus pores were experimentally shown to exhibit a translocation ratchet mechanism. Here we designed a synthetic translocation ratchet and quantified its efficiency as a nanopump. We measured the translocation frequency of DNA molecules through nanoporous membranes and showed that polycations at the side accelerated the translocation in a ratchet-like fashion. We investigated the ratchet efficiency according to geometrical and kinetic parameters and observed the ratchet to be only dependent on the size of the DNA molecule with a power law [Formula: see text]. A threshold length of 3 kbp was observed, below which the ratchet did not operate. We interpreted this threshold in a DNA looping model, which quantitatively explained our results.
Topics: Biological Transport; DNA; Fimbriae, Bacterial; Kinetics; Nanopores
PubMed: 35858428
DOI: 10.1073/pnas.2202527119 -
Nature Reviews. Microbiology Oct 2023
Topics: Fimbriae, Bacterial; Bacterial Adhesion
PubMed: 37495704
DOI: 10.1038/s41579-023-00957-4