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Clinical Microbiology Reviews Dec 2020The Gram-negative bacterium is responsible for deadly plague, a zoonotic disease established in stable foci in the Americas, Africa, and Eurasia. Its persistence in the... (Review)
Review
The Gram-negative bacterium is responsible for deadly plague, a zoonotic disease established in stable foci in the Americas, Africa, and Eurasia. Its persistence in the environment relies on the subtle balance between -contaminated soils, burrowing and nonburrowing mammals exhibiting variable degrees of plague susceptibility, and their associated fleas. Transmission from one host to another relies mainly on infected flea bites, inducing typical painful, enlarged lymph nodes referred to as buboes, followed by septicemic dissemination of the pathogen. In contrast, droplet inhalation after close contact with infected mammals induces primary pneumonic plague. Finally, the rarely reported consumption of contaminated raw meat causes pharyngeal and gastrointestinal plague. Point-of-care diagnosis, early antibiotic treatment, and confinement measures contribute to outbreak control despite residual mortality. Mandatory primary prevention relies on the active surveillance of established plague foci and ectoparasite control. Plague is acknowledged to have infected human populations for at least 5,000 years in Eurasia. genomes recovered from affected archaeological sites have suggested clonal evolution from a common ancestor shared with the closely related enteric pathogen and have indicated that gene acquisition during the Bronze Age conferred with ectoparasite transmissibility while maintaining its enteric transmissibility. Three historic pandemics, starting in 541 AD and continuing until today, have been described. At present, the third pandemic has become largely quiescent, with hundreds of human cases being reported mainly in a few impoverished African countries, where zoonotic plague is mostly transmitted to people by rodent-associated flea bites.
Topics: Animals; Archaeology; Clonal Evolution; Humans; Insect Vectors; Phylogeny; Plague; Population Surveillance; Rodentia; Siphonaptera; Soil Microbiology; Yersinia pestis
PubMed: 33298527
DOI: 10.1128/CMR.00044-19 -
Journal of Clinical Microbiology Jan 2018Plague is caused by and is not commonly encountered in clinics, although natural plague foci are widely distributed around the world. has been listed as a category A... (Review)
Review
Plague is caused by and is not commonly encountered in clinics, although natural plague foci are widely distributed around the world. has been listed as a category A bioterrorism agent. A neglected diagnosis will cause severe consequences. Therefore, this minireview briefly introduces the current understanding on and then focuses on practical aspects of plague, including clinical manifestations, diagnosis, treatment, and prevention, to alert clinicians about this notorious disease.
Topics: Animals; Anti-Bacterial Agents; Biological Warfare Agents; Humans; Microbiological Techniques; Plague; Rodentia; Siphonaptera; Yersinia pestis
PubMed: 29070654
DOI: 10.1128/JCM.01519-17 -
Genes and Immunity May 2019Plague is a vector-borne disease caused by Yersinia pestis. Transmitted by fleas from rodent reservoirs, Y. pestis emerged <6000 years ago from an enteric bacterial... (Review)
Review
Plague is a vector-borne disease caused by Yersinia pestis. Transmitted by fleas from rodent reservoirs, Y. pestis emerged <6000 years ago from an enteric bacterial ancestor through events of gene gain and genome reduction. It is a highly remarkable model for the understanding of pathogenic bacteria evolution, and a major concern for public health as highlighted by recent human outbreaks. A complex set of virulence determinants, including the Yersinia outer-membrane proteins (Yops), the broad-range protease Pla, pathogen-associated molecular patterns (PAMPs), and iron capture systems play critical roles in the molecular strategies that Y. pestis employs to subvert the human immune system, allowing unrestricted bacterial replication in lymph nodes (bubonic plague) and in lungs (pneumonic plague). Some of these immunogenic proteins as well as the capsular antigen F1 are exploited for diagnostic purposes, which are critical in the context of the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and <48 h for pneumonic plague). Here, we review recent research advances on Y. pestis evolution, virulence factor function, bacterial strategies to subvert mammalian innate immune responses, vaccination, and problems associated with pneumonic plague diagnosis.
Topics: Animals; Evolution, Molecular; Humans; Plague; Virulence Factors; Yersinia pestis
PubMed: 30940874
DOI: 10.1038/s41435-019-0065-0 -
Viruses Jul 2021Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using strains EV76 and KIM D27 as...
Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for . The host range of fEV-1 was restricted strictly to strains, while that of fD1 also included other members of Enterobacterales such as and . In this study, we present the life cycles, genomes, and proteomes of two myoviruses, fEV-1 and fD1.
Topics: Bacteriophages; Finland; Genome, Viral; Host Specificity; Microscopy, Electron, Transmission; Proteome; Sewage; Yersinia pestis
PubMed: 34372590
DOI: 10.3390/v13071384 -
Biomolecules May 2021Plague-a deadly disease caused by the bacterium -is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague,... (Review)
Review
Plague-a deadly disease caused by the bacterium -is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.
Topics: Animals; Anti-Bacterial Agents; Host Microbial Interactions; Humans; Immunotherapy; Plague; Vaccines; Yersinia pestis
PubMed: 34065940
DOI: 10.3390/biom11050724 -
Frontiers in Cellular and Infection... 2013The outer membrane protease Pla belongs to the omptin protease family spread by horizontal gene transfer into Gram-negative bacteria that infect animals or plants. Pla... (Review)
Review
The outer membrane protease Pla belongs to the omptin protease family spread by horizontal gene transfer into Gram-negative bacteria that infect animals or plants. Pla has adapted to support the life style of the plague bacterium Yersinia pestis. Pla has a β-barrel fold with 10 membrane-spanning β strands and five surface loops, and the barrel surface contains bound lipopolysaccharide (LPS) that is critical for the conformation and the activity of Pla. The biological activity of Pla is influenced by the structure of the surface loops around the active site groove and by temperature-induced LPS modifications. Several of the putative virulence-related functions documented for Pla in vitro address control of the human hemostatic system, i.e., coagulation and fibrinolysis. Pla activates human plasminogen to the serine protease plasmin and activates the physiological plasminogen activator urokinase. Pla also inactivates the protease inhibitors alpha-2-antiplasmin and plasminogen activator inhibitor 1 (PAI-1) and prevents the activation of thrombin-activatable fibrinolysis inhibitor (TAFI). These functions enhance uncontrolled fibrinolysis which is thought to improve Y. pestis dissemination and survival in the mammalian host, and lowered fibrin(ogen) deposition has indeed been observed in mice infected with Pla-positive Y. pestis. However, Pla also inactivates an anticoagulant, the tissue factor (TF) pathway inhibitor, which should increase fibrin formation and clotting. Thus, Pla and Y. pestis have complex interactions with the hemostatic system. Y. pestis modifies its LPS upon transfer to the mammalian host and we hypothesize that the contrasting biological activities of Pla in coagulation and fibrinolysis are influenced by LPS changes during infection.
Topics: Animals; Bacterial Proteins; Blood Coagulation; Endotoxins; Fibrinolysis; Humans; Lipopolysaccharides; Mice; Plasminogen Activators; Virulence Factors; Yersinia pestis
PubMed: 23898467
DOI: 10.3389/fcimb.2013.00035 -
Proceedings of the National Academy of... Apr 2022The bacterial pathogen Yersinia pestis gave rise to devastating outbreaks throughout human history, and ancient DNA evidence has shown it afflicted human populations as...
The bacterial pathogen Yersinia pestis gave rise to devastating outbreaks throughout human history, and ancient DNA evidence has shown it afflicted human populations as far back as the Neolithic. Y. pestis genomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to its emergence from a Yersinia pseudotuberculosis-like progenitor; however, the number of reconstructed LNBA genomes are too few to explore its diversity during this critical period of development. Here, we present 17 Y. pestis genomes dating to 5,000 to 2,500 y BP from a wide geographic expanse across Eurasia. This increased dataset enabled us to explore correlations between temporal, geographical, and genetic distance. Our results suggest a nonflea-adapted and potentially extinct single lineage that persisted over millennia without significant parallel diversification, accompanied by rapid dispersal across continents throughout this period, a trend not observed in other pathogens for which ancient genomes are available. A stepwise pattern of gene loss provides further clues on its early evolution and potential adaptation. We also discover the presence of the flea-adapted form of Y. pestis in Bronze Age Iberia, previously only identified in in the Caucasus and the Volga regions, suggesting a much wider geographic spread of this form of Y. pestis. Together, these data reveal the dynamic nature of plague’s formative years in terms of its early evolution and ecology.
Topics: Animal Husbandry; Animals; DNA, Ancient; Genetic Variation; Genome, Bacterial; History, Ancient; Human Migration; Humans; Phylogeny; Plague; Yersinia pestis
PubMed: 35412864
DOI: 10.1073/pnas.2116722119 -
Current Opinion in Infectious Diseases Jun 2022Pathogenic Yersinia have been a productive model system for studying bacterial pathogenesis. Hallmark contributions of Yersinia research to medical microbiology are... (Review)
Review
PURPOSE OF REVIEW
Pathogenic Yersinia have been a productive model system for studying bacterial pathogenesis. Hallmark contributions of Yersinia research to medical microbiology are legion and include: (i) the first identification of the role of plasmids in virulence, (ii) the important mechanism of iron acquisition from the host, (iii) the first identification of bacterial surface proteins required for host cell invasion, (iv) the archetypical type III secretion system, and (v) elucidation of the role of genomic reduction in the evolutionary trajectory from a fairly innocuous pathogen to a highly virulent species.
RECENT FINDINGS
The outer membrane (OM) protein Ail (attachment invasion locus) was identified over 30 years ago as an invasin-like protein. Recent work on Ail continues to provide insights into Gram-negative pathogenesis. This review is a synopsis of the role of Ail in invasion, serum resistance, OM stability, thermosensing, and vaccine development.
SUMMARY
Ail is shown to be an essential virulence factor with multiple roles in pathogenesis. The recent adaptation of Yersinia pestis to high virulence, which included genomic reduction to eliminate redundant protein functions, is a model to understand the emergence of new bacterial pathogens.
Topics: Bacterial Outer Membrane Proteins; Bacterial Proteins; Humans; Virulence; Virulence Factors; Yersinia pestis
PubMed: 35665712
DOI: 10.1097/QCO.0000000000000830 -
Molecular & Cellular Proteomics : MCP 2021Plague is a zoonotic disease that primarily infects rodents via fleabite. Transmission from flea to host niches requires rapid adaption of Yersinia pestis to the outer...
Plague is a zoonotic disease that primarily infects rodents via fleabite. Transmission from flea to host niches requires rapid adaption of Yersinia pestis to the outer environments to establish infection. Here, quantitative proteome and secretome analyses of Y. pestis grown under conditions mimicking the two typical niches, i.e., the mammalian host (Mh) and the flea vector (Fv), were performed to understand the adaption strategies of this deadly pathogen. A secretome of Y. pestis containing 308 proteins has been identified using TMT-labeling mass spectrometry analysis. Although some proteins are known to be secreted, such as the type III secretion substrates, PsaA and F1 antigen, most of them were found to be secretory proteins for the first time. Comparative proteomic analysis showed that membrane proteins, chaperonins and stress response proteins are significantly upregulated under the Mh condition, among which the previously uncharacterized proteins YP_3416∼YP_3418 are remarkable because they cannot only be secreted but also translocated into HeLa cells by Y. pestis. We further demonstrated that the purified YP_3416 and YP_3418 exhibited E3 ubiquitin ligase activity in in vitro ubiquitination assay and yp_3416∼3418 deletion mutant of Y. pestis showed significant virulence attenuation in mice. Taken together, our results represent the first Y. pestis secretome, which will promote the better understanding of Y. pestis pathogenesis, as well as the development of new strategies for treatment and prevention of plague.
Topics: Animals; Bacterial Proteins; Female; HeLa Cells; Humans; Mice, Inbred BALB C; Mutation; Plague; Proteomics; Secretome; Ubiquitin-Protein Ligases; Virulence; Yersinia pestis; Mice
PubMed: 33631294
DOI: 10.1016/j.mcpro.2021.100066 -
Clinical Microbiology Reviews Jan 1997Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has had devastating effects on the human population throughout history. Disappearance of... (Review)
Review
Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has had devastating effects on the human population throughout history. Disappearance of the disease is unlikely due to the wide range of mammalian hosts and their attendant fleas. The flea/rodent life cycle of Y. pestis, a gram-negative obligate pathogen, exposes it to very different environmental conditions and has resulted in some novel traits facilitating transmission and infection. Studies characterizing virulence determinants of Y. pestis have identified novel mechanisms for overcoming host defenses. Regulatory systems controlling the expression of some of these virulence factors have proven quite complex. These areas of research have provide new insights into the host-parasite relationship. This review will update our present understanding of the history, etiology, epidemiology, clinical aspects, and public health issues of plague.
Topics: Amino Acid Sequence; Animals; Animals, Domestic; Animals, Wild; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Toxins; Disease Reservoirs; Gene Expression Regulation, Bacterial; Genes, Bacterial; Global Health; History, 19th Century; History, Ancient; History, Medieval; Humans; Incidence; Insect Vectors; Molecular Sequence Data; Plague; Siphonaptera; United States; Virulence; Yersinia pestis
PubMed: 8993858
DOI: 10.1128/CMR.10.1.35