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Special Issue "Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery"

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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 10341

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Special Issue Editor

Dr. Yury Belyi

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Guest Editor

Gamaleya Research Centre for Epidemiology and Microbiology, Moscow 123098, Russia
Interests: Legionella; Clostridium difficile; toxin, bacterial effector; secretion system; virulence mechanism; infectious disease; pathogenesis

Special Issue Information

Dear Colleagues,

In the next year, microbiologists will acknowledge the 45th anniversary of the first description of Legionella pneumophila and the establishment of its role as an infectious agent of a human disease (McDade et al., 1977). The amazing achievements that followed include deciphering of the virulence of the bacterium as an interplay of highly specialised molecules synthesised inside the microorganism and delivered to eukaryotic hosts. This paradigm soon became widely adopted as a general concept of bacterium–host cell interaction, and Legionella has been recognised as a model organism. Synthesised by Legionella, biomolecules turned out to be remarkably diverse in their nature, mechanisms, structures, targets and their effects on eukaryotic cell physiology. Their concerted action shapes the virulence capability of the pathogen and results in the fine modulation of host cell activities, ultimately allowing successful proliferation of the bacterium inside the occupied niche. Excellent reviews and exciting experimental papers are available and are dedicated to processes manipulated by Legionella products. However, in this Special Issue, I would like to “come back to the roots” and to illuminate the individual properties of the biomolecules—effectors, nucleic acids, enzymes, microbial surface structures— that are created for the smooth running of the virulence machinery.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: biochemistry, genetics, molecular biology, and structural biology. I look forward to receiving your contributions.

Dr. Yury Belyi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Legionella
protein effector
enzyme
virulence
secretion system
molecular mechanism

Published Papers (6 papers)

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Editorial

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Open AccessEditorial

Legionella Research: Still Many Miles to Go

Yury Belyi

Biomolecules 2023, 13(5), 775; https://doi.org/10.3390/biom13050775 - 29 Apr 2023

Viewed by 562

Abstract

Legionella is a widespread Gram-negative bacterium occurring in water reservoirs and soils [...] Full article

(This article belongs to the Special Issue Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery)

Research

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Open AccessArticle

Zinc Metalloprotease ProA from Legionella pneumophila Inhibits the Pro-Inflammatory Host Response by Degradation of Bacterial Flagellin

and

Biomolecules 2022, 12(5), 624; https://doi.org/10.3390/biom12050624 - 22 Apr 2022

Cited by 4 | Viewed by 1679

Abstract

The environmental bacterium Legionella pneumophila is an intracellular pathogen of various protozoan hosts and able to cause Legionnaires’ disease, a severe pneumonia in humans. By encoding a wide selection of virulence factors, the infectious agent possesses several strategies to manipulate its host cells and evade immune detection. In the present study, we demonstrate that the L. pneumophila zinc metalloprotease ProA functions as a modulator of flagellin-mediated TLR5 stimulation and subsequent activation of the pro-inflammatory NF-κB pathway. We found ProA to be capable of directly degrading immunogenic FlaA monomers but not the polymeric form of bacterial flagella. These results indicate a role of the protease in antagonizing immune stimulation, which was further substantiated in HEK-Blue^TM hTLR5 Detection assays. Addition of purified proteins, bacterial suspensions of L. pneumophila mutant strains as well as supernatants of human lung tissue explant infection to this reporter cell line demonstrated that ProA specifically decreases the TLR5 response via FlaA degradation. Conclusively, the zinc metalloprotease ProA serves as a powerful regulator of exogenous flagellin and presumably creates an important advantage for L. pneumophila proliferation in mammalian hosts by promoting immune evasion. Full article

(This article belongs to the Special Issue Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery)

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Open AccessFeature PaperArticle

Characterization of a Novel Regulator of Biofilm Formation in the Pathogen Legionella pneumophila

Courtney Marin

Ogan K. Kumova

and

Shira Ninio

Biomolecules 2022, 12(2), 225; https://doi.org/10.3390/biom12020225 - 27 Jan 2022

Cited by 4 | Viewed by 2326

Abstract

Legionella pneumophila is a Gram-negative, facultative intracellular pathogen that causes severe pneumonia known as Legionnaires’ disease. The bacterium causes disease when contaminated water is aerosolized and subsequently inhaled by individuals, which allows the bacteria to gain access to the lungs, where they infect alveolar macrophages. L. pneumophila is ubiquitous in the environment, where it survives by growing in biofilms, intracellularly within protozoa, and planktonically. Biofilms are a major concern for public health because they provide a protective niche that allows for the continuous leaching of bacteria into the water supply. In addition, biofilms enhance the survival of the bacteria by increasing resistance to temperature fluctuations and antimicrobial agents. Currently, there is little known about biofilm formation and regulation by L. pneumophila. Here, we present evidence of a specific gene, bffA, which appears to be involved in the regulation of motility, biofilm formation, cellular replication, and virulence of L. pneumophila. A strain lacking bffA has an enhanced biofilm formation phenotype, forming biofilms that are both faster and thicker than wild type. Additionally, the knockout strain has significantly reduced motility, enhanced uptake into amoebae, and altered growth kinetics on solid media. Our data suggest a potential role for bffA in signaling pathways that govern changes in growth rate and motility in response to environmental conditions. Full article

(This article belongs to the Special Issue Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery)

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Open AccessEditor’s ChoiceArticle

The Functional Differences between the GroEL Chaperonin of Escherichia coli and the HtpB Chaperonin of Legionella pneumophila Can Be Mapped to Specific Amino Acid Residues

Karla N. Valenzuela-Valderas

Gabriel Moreno-Hagelsieb

John R. Rohde

and

Rafael A. Garduño

Biomolecules 2022, 12(1), 59; https://doi.org/10.3390/biom12010059 - 31 Dec 2021

Cited by 1 | Viewed by 1457

Abstract

Group I chaperonins are a highly conserved family of essential proteins that self-assemble into molecular nanoboxes that mediate the folding of cytoplasmic proteins in bacteria and organelles. GroEL, the chaperonin of Escherichia coli, is the archetype of the family. Protein folding-independent functions have been described for numerous chaperonins, including HtpB, the chaperonin of the bacterial pathogen Legionella pneumophila. Several protein folding-independent functions attributed to HtpB are not shared by GroEL, suggesting that differences in the amino acid (aa) sequence between these two proteins could correlate with functional differences. GroEL and HtpB differ in 137 scattered aa positions. Using the Evolutionary Trace (ET) bioinformatics method, site-directed mutagenesis, and a functional reporter test based upon a yeast-two-hybrid interaction with the eukaryotic protein ECM29, it was determined that out of those 137 aa, ten (M68, M212, S236, K298, N507 and the cluster AEHKD in positions 471-475) were involved in the interaction of HtpB with ECM29. GroEL was completely unable to interact with ECM29, but when GroEL was modified at those 10 aa positions, to display the HtpB aa, it acquired a weak ability to interact with ECM29. This constitutes proof of concept that the unique functional abilities of HtpB can be mapped to specific aa positions. Full article

(This article belongs to the Special Issue Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery)

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Open AccessEditor’s ChoiceArticle

Structural and Functional Characterization of Legionella pneumophila Effector MavL

Engku Nuraishah Huda E. Zainudin

Elizabeth L. Hartland

and

Miroslaw Cygler

Biomolecules 2021, 11(12), 1802; https://doi.org/10.3390/biom11121802 - 30 Nov 2021

Cited by 4 | Viewed by 1892

Abstract

Legionella pneumophila is a Gram-negative intracellular pathogen that causes Legionnaires’ disease in elderly or immunocompromised individuals. This bacterium relies on the Dot/Icm (Defective in organelle trafficking/Intracellular multiplication) Type IV Secretion System (T4SS) and a large (>330) set of effector proteins to colonize the host cell. The structural variability of these effectors allows them to disrupt many host processes. Herein, we report the crystal structure of MavL to 2.65 Å resolution. MavL adopts an ADP-ribosyltransferase (ART) fold and contains the distinctive ligand-binding cleft of ART proteins. Indeed, MavL binds ADP-ribose with Kd of 13 µM. Structural overlay of MavL with poly-(ADP-ribose) glycohydrolases (PARGs) revealed a pair of aspartate residues in MavL that align with the catalytic glutamates in PARGs. MavL also aligns with ADP-ribose “reader” proteins (proteins that recognize ADP-ribose). Since no glycohydrolase activity was observed when incubated in the presence of ADP-ribosylated PARP1, MavL may play a role as a signaling protein that binds ADP-ribose. An interaction between MavL and the mammalian ubiquitin-conjugating enzyme UBE2Q1 was revealed by yeast two-hybrid and co-immunoprecipitation experiments. This work provides structural and molecular insights to guide biochemical studies aimed at elucidating the function of MavL. Our findings support the notion that ubiquitination and ADP-ribosylation are global modifications exploited by L. pneumophila. Full article

(This article belongs to the Special Issue Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery)

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Review

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Open AccessReview

Glycosylating Effectors of Legionella pneumophila: Finding the Sweet Spots for Host Cell Subversion

Yury Belyi

Nadya Levanova

and

Gunnar N. Schroeder

Biomolecules 2022, 12(2), 255; https://doi.org/10.3390/biom12020255 - 04 Feb 2022

Cited by 1 | Viewed by 1544

Abstract

Work over the past two decades clearly defined a significant role of glycosyltransferase effectors in the infection strategy of the Gram-negative, respiratory pathogen Legionella pneumophila. Identification of the glucosyltransferase effectors Lgt1-3, specifically modifying elongation factor eEF1A, disclosed a novel mechanism of host protein synthesis manipulation by pathogens and illuminated its impact on the physiological state of the target cell, in particular cell cycle progression and immune and stress responses. Recent characterization of SetA as a general O-glucosyltransferase with a wide range of targets including the proteins Rab1 and Snx1, mediators of membrane transport processes, and the discovery of new types of glycosyltransferases such as LtpM and SidI indicate that the vast effector arsenal might still hold more so-far unrecognized family members with new catalytic features and substrates. In this article, we review our current knowledge regarding these fascinating biomolecules and discuss their role in introducing new or overriding endogenous post-translational regulatory mechanisms enabling the subversion of eukaryotic cells by L. pneumophila. Full article

(This article belongs to the Special Issue Biomolecules of Legionella – Tiny Parts Building the Virulence Machinery)

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