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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 -
The American Journal of Medicine Feb 2021During the fourteenth century, the bubonic plague or Black Death killed more than one third of Europe or 25 million people. Those afflicted died quickly and horribly... (Review)
Review
During the fourteenth century, the bubonic plague or Black Death killed more than one third of Europe or 25 million people. Those afflicted died quickly and horribly from an unseen menace, spiking high fevers with suppurative buboes (swellings). Its causative agent is Yersinia pestis, creating recurrent plague cycles from the Bronze Age into modern-day California and Mongolia. Plague remains endemic in Madagascar, Congo, and Peru. This history of medicine review highlights plague events across the centuries. Transmission is by fleas carried on rats, although new theories include via human body lice and infected grain. We discuss symptomatology and treatment options. Pneumonic plague can be weaponized for bioterrorism, highlighting the importance of understanding its clinical syndromes. Carriers of recessive familial Mediterranean fever (FMF) mutations have natural immunity against Y. pestis. During the Black Death, Jews were blamed for the bubonic plague, perhaps because Jews carried FMF mutations and died at lower plague rates than Christians. Blaming minorities for epidemics echoes across history into our current coronavirus pandemic and provides insightful lessons for managing and improving its outcomes.
Topics: COVID-19; History, Medieval; Humans; Pandemics; Plague
PubMed: 32979306
DOI: 10.1016/j.amjmed.2020.08.019 -
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 -
Nature Nov 2022Infectious diseases are among the strongest selective pressures driving human evolution. This includes the single greatest mortality event in recorded history, the first...
Infectious diseases are among the strongest selective pressures driving human evolution. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.
Topics: Humans; Aminopeptidases; DNA, Ancient; Plague; Yersinia pestis; Selection, Genetic; Europe; Immunity; Datasets as Topic; Genetic Predisposition to Disease; London; Denmark
PubMed: 36261521
DOI: 10.1038/s41586-022-05349-x -
Virulence Dec 2024The genus includes human, animal, insect, and plant pathogens as well as many symbionts and harmless bacteria. Within this genus are and the complex, with four human... (Review)
Review
The genus includes human, animal, insect, and plant pathogens as well as many symbionts and harmless bacteria. Within this genus are and the complex, with four human pathogenic species that are highly related at the genomic level including the causative agent of plague, . Extensive laboratory, field work, and clinical research have been conducted to understand the underlying pathogenesis and zoonotic transmission of these pathogens. There are presently more than 500 whole genome sequences from which an evolutionary footprint can be developed that details shared and unique virulence properties. Whereas the virulence of now seems in apparent homoeostasis within its flea transmission cycle, substantial evolutionary changes that affect transmission and disease severity continue to ndergo apparent selective pressure within the other that cause intestinal diseases. In this review, we will summarize the present understanding of the virulence and pathogenesis of , highlighting shared mechanisms of virulence and the differences that determine the infection niche and disease severity.
Topics: Animals; Humans; Yersinia; Virulence; Yersinia pestis; Plague; Yersinia Infections
PubMed: 38389313
DOI: 10.1080/21505594.2024.2316439 -
Science Advances Mar 2023Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines have emerged as an effective vaccination strategy. Although currently applied toward viral pathogens, data...
Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines have emerged as an effective vaccination strategy. Although currently applied toward viral pathogens, data concerning the platform's effectiveness against bacterial pathogens are limited. Here, we developed an effective mRNA-LNP vaccine against a lethal bacterial pathogen by optimizing mRNA payload guanine and cytosine content and antigen design. We designed a nucleoside-modified mRNA-LNP vaccine based on the bacterial F1 capsule antigen, a major protective component of , the etiological agent of plague. Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of humankind. Now, the disease is treated effectively with antibiotics; however, in the case of a multiple-antibiotic-resistant strain outbreak, alternative countermeasures are required. Our mRNA-LNP vaccine elicited humoral and cellular immunological responses in C57BL/6 mice and conferred rapid, full protection against lethal infection after a single dose. These data open avenues for urgently needed effective antibacterial vaccines.
Topics: Mice; Animals; Plague; Plague Vaccine; Bacterial Proteins; Mice, Inbred C57BL; Yersinia pestis; Antigens, Bacterial
PubMed: 36888708
DOI: 10.1126/sciadv.adg1036 -
Pediatric Radiology Jul 2020
Topics: Animals; Books; Europe; History, 17th Century; History, 18th Century; History, Medieval; Humans; Pediatrics; Plague; Radiology
PubMed: 32474771
DOI: 10.1007/s00247-020-04719-9 -
Emerging Infectious Diseases 2021Knowing whether human corpses can transmit plague will inform policies for handling the bodies of those who have died of the disease. We analyzed the literature to... (Review)
Review
Knowing whether human corpses can transmit plague will inform policies for handling the bodies of those who have died of the disease. We analyzed the literature to evaluate risk for transmission of Yersinia pestis, the causative agent of plague, from human corpses and animal carcasses. Because we could not find direct evidence of transmission, we described a transmission pathway and assessed the potential for transmission at each step. We examined 3 potential sources of infection: body fluids of living plague patients, infected corpses and carcasses, and body fluids of infected corpses. We concluded that pneumonic plague can be transmitted by intensive handling of the corpse or carcass, presumably through the inhalation of respiratory droplets, and that bubonic plague can be transmitted by blood-to-blood contact with the body fluids of a corpse or carcass. These findings should inform precautions taken by those handling the bodies of persons or animals that died of plague.
Topics: Animals; Cadaver; Humans; Plague; Yersinia pestis
PubMed: 34286686
DOI: 10.3201/eid2708.200136 -
Science (New York, N.Y.) Nov 2018Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via...
Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the effector protein YopJ elicits RIPK1- and caspase-8-dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome-dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.
Topics: Animals; Apoptosis Regulatory Proteins; Bacterial Proteins; Caspase 8; Cell Death; Host-Pathogen Interactions; Humans; I-kappa B Kinase; Inflammasomes; Intracellular Signaling Peptides and Proteins; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphate-Binding Proteins; Plague; Proteolysis
PubMed: 30361383
DOI: 10.1126/science.aau2818