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Annual Review of Pathology Jan 2020species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of in... (Review)
Review
species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of in 1977, four decades of research on biology and Legionnaires' disease have brought important insights into the biology of the bacteria and the molecular mechanisms that these intracellular pathogens use to cause disease in humans. Nowadays, species constitute a remarkable model of bacterial adaptation, with a genus genome shaped by their close coevolution with amoebae and an ability to exploit many hosts and signaling pathways through the secretion of a myriad of effector proteins, many of which have a eukaryotic origin. This review aims to discuss current knowledge of infection mechanisms and future research directions to be taken that might answer the many remaining open questions. This research will without a doubt be a terrific scientific journey worth taking.
Topics: Adaptation, Physiological; Amoeba; Eukaryotic Cells; Host-Pathogen Interactions; Humans; Legionella; Legionella pneumophila; Legionnaires' Disease
PubMed: 31657966
DOI: 10.1146/annurev-pathmechdis-012419-032742 -
Clinical Microbiology Reviews Jul 2002There is still a low level of clinical awareness regarding Legionnaires' disease 25 years after it was first detected. The causative agents, legionellae, are freshwater... (Review)
Review
There is still a low level of clinical awareness regarding Legionnaires' disease 25 years after it was first detected. The causative agents, legionellae, are freshwater bacteria with a fascinating ecology. These bacteria are intracellular pathogens of freshwater protozoa and utilize a similar mechanism to infect human phagocytic cells. There have been major advances in delineating the pathogenesis of legionellae through the identification of genes which allow the organism to bypass the endocytic pathways of both protozoan and human cells. Other bacteria that may share this novel infectious process are Coxiella burnetti and Brucella spp. More than 40 species and numerous serogroups of legionellae have been identified. Most diagnostic tests are directed at the species that causes most of the reported human cases of legionellosis, L. pneumophila serogroup 1. For this reason, information on the incidence of human respiratory disease attributable to other species and serogroups of legionellae is lacking. Improvements in diagnostic tests such as the urine antigen assay have inadvertently caused a decrease in the use of culture to detect infection, resulting in incomplete surveillance for legionellosis. Large, focal outbreaks of Legionnaires' disease continue to occur worldwide, and there is a critical need for surveillance for travel-related legionellosis in the United States. There is optimism that newly developed guidelines and water treatment practices can greatly reduce the incidence of this preventable illness.
Topics: Animals; Humans; Legionella; Legionnaires' Disease; Research; Virulence
PubMed: 12097254
DOI: 10.1128/CMR.15.3.506-526.2002 -
Seminars in Cell & Developmental Biology Dec 2022Legionella pneumophila, a Gram-negative intracellular bacterium, is one of the major causes of Legionnaires' disease, a specific type of atypical pneumonia. Despite... (Review)
Review
Legionella pneumophila, a Gram-negative intracellular bacterium, is one of the major causes of Legionnaires' disease, a specific type of atypical pneumonia. Despite intensive research efforts that elucidated many relevant structural, molecular and medical insights into Legionella's pathogenicity, Legionnaires' disease continues to present an ongoing public health concern. Legionella's virulence is based on its ability to simultaneously hijack multiple molecular pathways of the host cell to ensure its fast replication and dissemination. Legionella usurps the host ubiquitin system through multiple effector proteins, using the advantage of both conventional and unconventional (phosphoribosyl-linked) ubiquitination, thus providing optimal conditions for its replication. In this review, we summarize the current understanding of L. pneumophila from medical, biochemical and molecular perspectives. We describe the clinical disease presentation, its diagnostics and treatment, as well as host-pathogen interactions, with the emphasis on the ability of Legionella to target the host ubiquitin system upon infection. Furthermore, the interdisciplinary use of innovative technologies enables better insights into the pathogenesis of Legionnaires' disease and provides new opportunities for its treatment and prevention.
Topics: Humans; Bacterial Proteins; Host-Pathogen Interactions; Legionella pneumophila; Legionnaires' Disease; Ubiquitin
PubMed: 35177348
DOI: 10.1016/j.semcdb.2022.02.008 -
Frontiers in Cellular and Infection... 2018
Topics: Acanthamoeba; Biomedical Research; DNA Mutational Analysis; Host-Pathogen Interactions; Legionella; Legionnaires' Disease; Microbial Viability; Virulence; Virulence Factors; Water Microbiology
PubMed: 30283746
DOI: 10.3389/fcimb.2018.00328 -
BMB Reports Jul 2022Ubiquitin is relatively modest in size but involves almost entire cellular signaling pathways. The primary role of ubiquitin is maintaining cellular protein homeostasis.... (Review)
Review
Ubiquitin is relatively modest in size but involves almost entire cellular signaling pathways. The primary role of ubiquitin is maintaining cellular protein homeostasis. Ubiquitination regulates the fate of target proteins using the proteasome- or autophagymediated degradation of ubiquitinated substrates, which can be either intracellular or foreign proteins from invading pathogens. Legionella, a gram-negative intracellular pathogen, hinders the host-ubiquitin system by translocating hundreds of effector proteins into the host cell's cytoplasm. In this review, we describe the current understanding of ubiquitin machinery from Legionella. We summarize structural and biochemical differences between the host-ubiquitin system and ubiquitin-related effectors of Legionella. Some of these effectors act much like canonical host-ubiquitin machinery, whereas others have distinctive structures and accomplish non-canonical ubiquitination via novel biochemical mechanisms. [BMB Reports 2022; 55(7): 316-322].
Topics: Bacterial Proteins; Legionella; Legionella pneumophila; Ubiquitin; Ubiquitination
PubMed: 35651329
DOI: 10.5483/BMBRep.2022.55.7.054 -
FEMS Microbiology Ecology Jul 2022Opportunistic pathogens belonging to the genus Legionella are among the most reported waterborne-associated pathogens in industrialized countries. Legionella colonize a... (Review)
Review
Opportunistic pathogens belonging to the genus Legionella are among the most reported waterborne-associated pathogens in industrialized countries. Legionella colonize a variety of engineered aquatic ecosystems and persist in biofilms where they interact with a multitude of other resident microorganisms. In this review, we assess how some of these interactions could be used to develop a biological-driven "probiotic" control approach against Legionella. We focus on: (i) mechanisms limiting the ability of Legionella to establish and replicate within some of their natural protozoan hosts; (ii) exploitative and interference competitive interactions between Legionella and other microorganisms; and (iii) the potential of predatory bacteria and phages against Legionella. This field is still emergent, and we therefore specifically highlight research for future investigations, and propose perspectives on the feasibility and public acceptance of a potential probiotic approach.
Topics: Biofilms; Ecosystem; Legionella; Legionella pneumophila; Probiotics
PubMed: 35679082
DOI: 10.1093/femsec/fiac071 -
Frontiers in Cellular and Infection... 2017The genus comprises more than 60 species. In particular, is known to cause severe illnesses in humans. Legionellaceae are ubiquitous inhabitants of aquatic... (Review)
Review
The genus comprises more than 60 species. In particular, is known to cause severe illnesses in humans. Legionellaceae are ubiquitous inhabitants of aquatic environments. Some Legionellaceae are motile and their motility is important to move around in habitats. Motility can be considered as a potential virulence factor as already shown for various human pathogens. The genes of the flagellar system, regulator and structural genes, are structured in hierarchical levels described as the flagellar regulon. Their expression is modulated by various environmental factors. For it was shown that the expression of genes of the flagellar regulon is modulated by the actual growth phase and temperature. Especially, flagellated are known to express genes during the transmissive phase of growth that are involved in the expression of virulence traits. It has been demonstrated that the alternative sigma-28 factor is part of the link between virulence expression and motility. In the following review, the structure of the flagellar regulon of is discussed and compared to other flagellar systems of different species. Recently, it has been described that and contain a second putative partial flagellar system. Hence, the report will focus on flagellated and non-flagellated strains, phylogenetic relationships, the role and function of the alternative sigma factor (FliA) and its anti-sigma-28 factor (FlgM).
Topics: Bacterial Proteins; Cell Movement; Flagella; Humans; Legionella; Phylogeny; Regulon; Sigma Factor; Virulence
PubMed: 29104863
DOI: 10.3389/fcimb.2017.00454 -
Scientific Reports Dec 2022The pathogenic Legionella bacteria are notorious for delivering numerous effector proteins into the host cell with the aim of disturbing and hijacking cellular processes...
The pathogenic Legionella bacteria are notorious for delivering numerous effector proteins into the host cell with the aim of disturbing and hijacking cellular processes for their benefit. Despite intensive studies, many effectors remain uncharacterized. Motivated by the richness of Legionella effector repertoires and their oftentimes atypical biochemistry, also by several known atypical Legionella effector kinases and pseudokinases discovered recently, we undertook an in silico survey and exploration of the pan-kinome of the Legionella genus, i.e., the union of the kinomes of individual species. In this study, we discovered 13 novel (pseudo)kinase families (all are potential effectors) with the use of non-standard bioinformatic approaches. Together with 16 known families, we present a catalog of effector and non-effector protein kinase-like families within Legionella, available at http://bioinfo.sggw.edu.pl/kintaro/ . We analyze and discuss the likely functional roles of the novel predicted kinases. Notably, some of the kinase families are also present in other bacterial taxa, including other pathogens, often phylogenetically very distant from Legionella. This work highlights Nature's ingeniousness in the pathogen-host arms race and offers a useful resource for the study of infection mechanisms.
Topics: Legionella; Protein Kinases; Computational Biology; Legionella pneumophila; Bacterial Proteins; Host-Pathogen Interactions
PubMed: 36526881
DOI: 10.1038/s41598-022-26109-x -
The ISME Journal Jan 2021The water-borne bacterium Legionella pneumophila is the causative agent of Legionnaires' disease. In the environment, the opportunistic pathogen colonizes different...
The water-borne bacterium Legionella pneumophila is the causative agent of Legionnaires' disease. In the environment, the opportunistic pathogen colonizes different niches, including free-living protozoa and biofilms. The physiological state(s) of sessile Legionella in biofilms and their functional consequences are not well understood. Using single-cell techniques and fluorescent growth rate probes as well as promoter reporters, we show here that sessile L. pneumophila exhibits phenotypic heterogeneity and adopts growing and nongrowing ("dormant") states in biofilms and microcolonies. Phenotypic heterogeneity is controlled by the Legionella quorum sensing (Lqs) system, the transcription factor LvbR, and the temperature. The Lqs system and LvbR determine the ratio between growing and nongrowing sessile subpopulations, as well as the frequency of growth resumption ("resuscitation") and microcolony formation of individual bacteria. Nongrowing L. pneumophila cells are metabolically active, express virulence genes and show tolerance toward antibiotics. Therefore, these sessile nongrowers are persisters. Taken together, the Lqs system, LvbR and the temperature control the phenotypic heterogeneity of sessile L. pneumophila, and these factors regulate the formation of a distinct subpopulation of nongrowing, antibiotic tolerant, virulent persisters. Hence, the biofilm niche of L. pneumophila has a profound impact on the ecology and virulence of this opportunistic pathogen.
Topics: Biofilms; Legionella; Legionella pneumophila; Quorum Sensing; Virulence
PubMed: 32951019
DOI: 10.1038/s41396-020-00774-0 -
Annals of Agricultural and... Dec 2021spp. are ubiquitous worldwide in natural water sources (rivers, lakes) as well as in man-made water systems (cooling towers, tap water, spas). The most common species...
INTRODUCTION AND OBJECTIVE
spp. are ubiquitous worldwide in natural water sources (rivers, lakes) as well as in man-made water systems (cooling towers, tap water, spas). The most common species causing the disease in humans is . Pathogenicity of is related to the genes associated with virulence. The study aimed to detect spp. DNA in man-made water systems, and to examine the presence of selected virulence genes () in -positive samples.
MATERIAL AND METHODS
A total of 52 water samples from hot and cold water systems collected from urban and rural areas were investigated for the presence of by polymerase chain reaction (PCR). The detection of three virulence loci ( and ) in water samples was investigated using PCR.
RESULTS
spp. was detected in over half the tested samples (55.77%), both in water from hot (55.88%) and cold (55.56%) water systems. Sequencing confirmed the presence of in the tested samples. Among all -positive isolates, at least one virulence gene was detected in the case of 55.17% (16/29) of environmental samples. The locus was most frequently present in all specimens.
CONCLUSIONS
The presence of , the causative agent of Legionnaires' disease, in hot and cold water systems from rural and urban localities, indicates a risk to public health. The occurrence of virulence genes in tested samples suggests that has the potential to cause human disease.
Topics: Humans; Legionella; Legionella pneumophila; Legionnaires' Disease; Virulence; Water; Water Microbiology
PubMed: 34969219
DOI: 10.26444/aaem/143745