One Health: navigating plague in Madagascar amidst COVID-19.

BACKGROUND: Africa sees the surge of plague cases in recent decades, with hotspots in the Democratic Republic of Congo, Madagascar, and Peru. A rodent-borne scourge, the bacterial infection known as plague is transmitted to humans via the sneaky bites of fleas, caused by Yersinia pestis. Bubonic plague has a case fatality rate of 20.8% with treatment, but in places such as Madagascar the mortality rate can increase to 40-70% without treatment. MAIN TEXT: Tragedy strikes in the Ambohidratrimo district as three lives are claimed by the plague outbreak and three more fight for survival in the hospitals, including one man in critical condition, from the Ambohimiadana, Antsaharasty, and Ampanotokana communes, bringing the total plague victims in the area to a grim to five. Presently, the biggest concern is the potential plague spread among humans during the ongoing COVID-19 pandemic. Effective disease control can be achieved through training and empowering local leaders and healthcare providers in rural areas, implementing strategies to reduce human-rodent interactions, promoting water, sanitation and hygiene practices (WASH) practices, and carrying out robust vector, reservoir and pest control, diversified animal surveillance along with human surveillance should be done to more extensively to fill the lacunae of knowledge regarding the animal to human transmission. The lack of diagnostic laboratories equipped represents a major hurdle in the early detection of plague in rural areas. To effectively combat plague, these tests must be made more widely available. Additionally, raising awareness among the general population through various means such as campaigns, posters and social media about the signs, symptoms, prevention, and infection control during funerals would greatly decrease the number of cases. Furthermore, healthcare professionals should be trained on the latest methods of identifying cases, controlling infections and protecting themselves from the disease. CONCLUSIONS: Despite being endemic to Madagascar, the outbreak's pace is unparalleled, and it may spread to non-endemic areas. The utilization of a One Health strategy that encompasses various disciplines is crucial for minimizing catastrophe risk, antibiotic resistance, and outbreak readiness. Collaboration across sectors and proper planning ensures efficient and consistent communication, risk management, and credibility during disease outbreaks.

Oridonin supplementation in rabbits may help to improve the outcome of induced atherosclerosis via autophagy induction.

BACKGROUND AND AIM: Inflammation plays a crucial role in the development of atherosclerotic plague. Oridonin is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens. It is a natural terpenoids that is known as a strong anti-inflammatory supplement by acting as a potent inhibitor of the TXNIP/NLRP3 pathway. Hence, it can reduce the severity of inflammation and improve the outcome of atherosclerotic changes. This study aims to evaluate the anti-inflammatory effects of oridonin in the progression of atherosclerotic plague in rabbits. METHODS: Sixty-three male rabbits were included. The rabbits were randomly assigned to one of the three study groups (21 rabbits in each group), normal control diet (NC) fed normal diet for 8 weeks, atherogenic control (AC) fed atherogenic diet (2% cholesterol-enriched diet) for 8 weeks, and oridonin treated group (OT) fed atherogenic diet (2% cholesterol-enriched diet) with oridonin (purity 94%, Sigma-Aldrich, USA) at 20 mg/kg orally daily for 8 weeks. After the end of the study, blood and tissue samples were collected for analysis of various markers of inflammation and atherosclerotic plaque progression. RESULTS: Serum lipids showed a statistically significant improvement in terms of reduction in total cholesterol and low-density lipoprotein (LDL) in the OT group compared to the AC group. This was associated with a significant reduction in serum F2-isoprostane (marker of inflammation) and LC3B (marker of tissue autophagy) between the OT group compared to the AC group. There was also a significant reduction in NLRP3 inflammasome RNA expression in OT group, P<0.001. CONCLUSIONS: In animal model, with atherogenic diet, oridonin supplementation can significantly improve the outcome of atherosclerosis by its strong anti-inflammatory action.

[Genetic legacy of the Black Death pandemic]. / Les traces génétiques de la peste noire - Chroniques génomiques.

Genetic analysis of human populations before and after the great plague pandemic in the late Middle Ages reveals immune-related loci at which specific alleles have been selected because they conferred (partial) resistance to the pathogen. Some of these alleles are associated with susceptibility to present-day immune diseases, illustrating the complex interplay between genes, environment and the immune system.

A frameshift in Yersinia pestis rcsD alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles.

Multiple genetic changes in the enteric pathogen Yersinia pseudotuberculosis have driven the emergence of Yesinia pestis, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of rcsA, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating Y. pestis flea-borne transmission. Additionally, rcsD, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this rcsD mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the rcsD frameshift mutation followed the emergence of rcsA pseudogenization. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the pgm locus in modern lineages of Y. pestis. Taken together, our findings suggest that a frameshift mutation in rcsD is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.

Yersinia pestis, the agent responsible for the plague, emerged 6,000 to 7,000 years ago from Yersinia pseudotuberculosis, another type of bacteria which still exists today. Although they are highly similar genetically, these two species are strikingly different. While Y. pseudotuberculosis spreads via food and water and causes mild stomach distress, Y. pestis uses fleas to infect new hosts and has killed millions. A small set of genetic changes has contributed to the emergence of Y. pestis by allowing it to thrive inside a flea and maximise its transmission. In particular, some of these mutations have led to the bacteria being able to come together to form a sticky layer that adheres to the gut of the insect, with this 'biofilm' stopping the flea from feeding on blood. The starving flea keeps trying to feed, and with each bite comes another opportunity for Y. pestis to jump host. However, it remains unclear exactly how the mutations have influenced biofilm formation to allow for this new transmission mechanism to take place. To examine this phenomenon, Guo et al. focused on rcsD, a gene that codes for a component of the signalling system that controls biofilm creation. In Y. pestis this sequence has been mutated to become a 'pseudogene', a type of sequence which is often thought to be non-functional. However, the experiments showed that, in Y. pestis, rcsD could produce small amounts of a full-length RcsD protein similar to the one found in Y. pseudotuberculosis. However, the gene mostly produces a short 'RcsD-Hpt' protein that can, in turn, alter the expression of many genes, including those that decrease biofilm formation. This may prove to be beneficial for Y. pestis, for example when the bacteria switches from living in fleas to living in humans, where it does not require a biofilm. Guo et al. further investigated the impact of rcsD becoming a pseudogene inY. pestis, showing that if normal amounts of the full-length RcsD protein are produced, the bacteria quickly lose the gene that allows them to form biofilm in fleas, and cause disease in humans. In fact, additional analyses revealed that all sequenced strains of ancient and modern Y. pestis bacteria can produce RcsD-Hpt, even if they do not carry the same exact rcsD mutation. Overall, these results indicate that rcsD turning into a pseudogene marked an important step in the emergence of Y. pestis strains that can cause lasting plague outbreaks. They also point towards pseudogenes having more important roles in evolution than previously thought.

A Widefield Light Microscopy-Based Approach Provides Further Insights into the Colonization of the Flea Proventriculus by Yersinia pestis.

Yersinia pestis (the agent of flea-borne plague) must obstruct the flea's proventriculus to maintain transmission to a mammalian host. To this end, Y. pestis must consolidate a mass that entrapped Y. pestis within the proventriculus very early after its ingestion. We developed a semiautomated fluorescent image analysis method and used it to monitor and compare colonization of the flea proventriculus by a fully competent flea-blocking Y. pestis strain, a partially competent strain, and a noncompetent strain. Our data suggested that flea blockage results primarily from the replication of Y. pestis trapped in the anterior half of the proventriculus. However, consolidation of the bacteria-entrapping mass and colonization of the entire proventricular lumen increased the likelihood of flea blockage. The data also showed that consolidation of the bacterial mass is not a prerequisite for colonization of the proventriculus but allowed Y. pestis to maintain itself in a large flea population for an extended period of time. Taken as the whole, the data suggest that a strategy targeting bacterial mass consolidation could significantly reduce the likelihood of Y. pestis being transmitted by fleas (due to gut blockage), but also the possibility of using fleas as a long-term reservoir. IMPORTANCE Yersinia pestis (the causative agent of plague) is one of the deadliest bacterial pathogens. It circulates primarily among rodent populations and their fleas. Better knowledge of the mechanisms leading to the flea-borne transmission of Y. pestis is likely to generate strategies for controlling or even eradicating this bacillus. It is known that Y. pestis obstructs the flea's foregut so that the insect starves, frantically bites its mammalian host, and regurgitates Y. pestis at the bite site. Here, we developed a semiautomated fluorescent image analysis method and used it to document and compare foregut colonization and disease progression in fleas infected with a fully competent flea-blocking Y. pestis strain, a partially competent strain, and a noncompetent strain. Overall, our data provided new insights into Y. pestis' obstruction of the proventriculus for transmission but also the ecology of plague.

Plague God Image in the Clinic.

This paper selects four dreams before and during COVID-19 which constellated the Plague God image in Chinese culture. The author argues that this shows evidence that the origins of the modern psyche, although hidden, are preserved and living within the ancient anima mundi.

Cet article sélectionne quatre rêves produits avant et pendant la pandémie de COVID-19 et qui montrent la constellation de l'image divine de la peste dans la culture Chinoise. L'auteur soutient que ceci montre la preuve que les origines de la psyché moderne, bien que cachées, sont préservées et vivantes au sein de l'ancien anima mundi.

El presente artículo selecciona cuatro sueños antes y durante la pandemia del COVID-19 que constelan la imagen del dios de la peste en la cultura China. El autor argumenta que esto demuestra que los orígenes de la psique moderna, aunque ocultos, se conservan y viven dentro de la antigua anima mundi.

The Transformation of Chinese Cultural Images of the Plague through Chinese Characters, Legends and Folkways.

The human experience of survival from a plague is about distinguishing the sick from the healthy as quickly as possible, establishing a barrier to stop the infection, and protecting healthy people. Nevertheless, the various quarantine rules and the acceptance and compliance of the population are a kind of battle between policy implementers and the public. This paper tries to understand how Chinese cultural attitudes (Henderson, 1984) unconsciously influence the Chinese people to be most cooperative with the strict containment and quarantine measures to confront the COVID-19 pandemic. This article begins with the Chinese characters, exemplified by the four characters of disease and plague, to discuss how the pictograph nature and spatial structural way profoundly shaped the cultural mind. Then, through plague-related Chinese legends, stories and folklore, the paper sets out the Chinese cultural attitudes which are also manifested in the analogical associations between disease, plague and seasons, the balance of the five elements of the universe and ghosts, gods and the government bureaucrats in the Kingdom of the Heaven. All of these approaches are well in line with Jung's method of associative amplification as a way to locate the archetypal wisdom that assures survival.

L'expérience humaine de survivre à la peste est de distinguer les malades des personnes saines aussi vite que possible, d'établir une barrière pour stopper l'infection, de protéger les personnes saines. Cependant les diverses règles sur la quarantaine et l'acceptation et la soumission de la population sont une sorte de bataille entre les personnes qui mettent en œuvre les mesures et le public. Cet article tente de comprendre comment les attitudes culturelles Chinoises (Henderson 1984) ont influencé inconsciemment le peuple Chinois, le rendant plus coopératif en ce qui concerne le confinement strict et les mesures de quarantaine pour faire face à la pandémie de COVID-19. Cet article commence avec les caractères Chinois, illustrés par les quatre caractères de la maladie et la peste, pour discuter comment le pictogramme de la nature et la façon de structurer l'espace ont profondément modelé la pensée culturelle. Ensuite, à travers des légendes, des histoires et le folklore Chinois traitant de la peste, l'article cerne les attitudes culturelles Chinoises. Ces attitudes sont également repérables dans les analogies entre la maladie, la peste et les saisons, l'équilibre des cinq éléments de l'univers, les esprits, les dieux et les bureaucrates gouvernementaux dans le Royaume des Cieux. Toutes ces approches sont bien en accord avec la méthode d'amplification associative de Jung en tant que manière de situer la sagesse archétypale qui permet la survie.

La experiencia humana de sobrevivir a una plaga consiste en distinguir lo antes posible a los enfermos de los sanos, establecer una barrera para detener la infección y proteger a las personas sanas. Sin embargo, las diversas normas de cuarentena y la aceptación y el cumplimiento por parte de la población son una especie de batalla entre los responsables políticos y el público. Este artículo trata de entender cómo las actitudes culturales chinas (Henderson 1984) influyen inconscientemente en el pueblo chino para que sea más cooperativo con las estrictas medidas de contención y cuarentena para hacer frente a la pandemia de COVID-19. El presente artículo comienza con los caracteres chinos, ejemplificados por los cuatro caracteres de la enfermedad y la peste, para analizar cómo la naturaleza pictográfica y la forma estructural espacial moldearon profundamente la mente cultural. A continuación, a través de leyendas, cuentos y folclore chinos relacionados con la peste, el artículo expone las actitudes culturales chinas que también se manifiestan en las asociaciones analógicas entre la enfermedad, la peste y las estaciones, el equilibrio de los cinco elementos del universo, y los fantasmas, los dioses y los burócratas del gobierno en el Reino de los Cielos. Todos estos planteamientos se ajustan bien al método de Jung de amplificación asociativa como vía de acceso a la sabiduría arquetípica que asegura la supervivencia.

Mechanism of pulmonary plague biphasic syndrome: inhibition or activation of NF-κB signaling pathway.

Background: Pneumonic plague is a fatal respiratory disease caused by Yersinia pestis. Time-course transcriptome analysis on the mechanism of pneumonic plague biphasic syndrome is lacking in the literature. Materials & methods: This study documented the disease course through bacterial load, histopathology, cytokine levels and flow cytometry. RNA-sequencing technology was used to investigate the global transcriptome profile of lung tissue in mice infected with Y. pestis. Results: Inflammation-related genes were significantly upregulated at 48 h post-infection, while genes related to cell adhesion and cytoskeletal structure were downregulated. Conclusion: NOD-like receptor and TNF signaling pathways play a plausible role in pneumonic plague biphasic syndrome and lung injury by controlling the activation and inhibition of the NF-κB signaling pathway.

CYP broth: a tool for Yersinia pestis isolation in ancient culture collections and field samples.

We developed a simple new selective LB-based medium, named CYP broth, suitable for recovering long-term stored Y. pestis subcultures and for isolation of Y. pestis strains from field-caught samples for the Plague surveillance. It aimed to inhibit the growth contaminating microorganisms and enrich Y. pestis growth through iron supplementation. The performance of CYP broth on microbial growth from different gram-negative and gram-positive strains from American Type Culture Collection (ATCC®) and other clinical isolates, field-caught rodent samples, and more importantly, on several vials of ancient Y. pestis subcultures was evaluated. Additionally, other pathogenic Yersinia species such as Y. pseudotuberculosis and Y. enterocolitica were also successfully isolated with CYP broth. Selectivity tests and bacterial growth performance on CYP broth (LB broth supplemented with Cefsulodine, Irgasan, Novobiocin, nystatin and ferrioxamine E) were evaluated in comparison with LB broth without additive; LB broth/CIN, LB broth/nystatin and with traditional agar media including LB agar without additive, and LB agar and Cefsulodin-Irgasan-Novobiocin Agar (CIN agar) supplemented with 50 µg/mL of nystatin. Of note, the CYP broth had a recovery twofold higher than those of the CIN supplemented media or other regular media. Additionally, selectivity tests and bacterial growth performance were also evaluated on CYP broth in the absence of ferrioxamine E. The cultures were incubated at 28 °C and visually inspected for microbiological growth analysis and O.D.625 nm measurement between 0 and 120 h. The presence and purity of Y. pestis growth were confirmed by bacteriophage and multiplex PCR tests. Altogether, CYP broth provides an enhanced growth of Y. pestis at 28 °C, while inhibiting contaminant microorganisms. The media is a simple, but powerful tool to improve the reactivation and decontamination of ancient Y. pestis culture collections and for the isolation of Y. pestis strains for the Plague surveillance from various backgrounds. KEY POINTS: • The newly described CYP broth improves the recuperation of ancient/contaminated Yersinia pestis culture collections • CYP broth was also efficient in reducing environmental contamination in field-capture samples, improving Y. pestis isolation • CYP broth can also be used for the isolation of Y. enterocolitica and Y. pseudotuberculosis.

Colonial rodent control in Tanganyika and the application of ecological frameworks.

ABSTRACTAt the end of the 1920s, Tanganyika Territory experienced several serious rodent outbreaks that threatened cotton and other grain production. At the same time, regular reports of pneumonic and bubonic plague occurred in the northern areas of Tanganyika. These events led the British colonial administration to dispatch several studies into rodent taxonomy and ecology in 1931 to determine the causes of rodent outbreaks and plague disease, and to control future outbreaks. The application of ecological frameworks to the control of rodent outbreaks and plague disease transmission in colonial Tanganyika Territory gradually moved from a view that prioritised 'ecological interrelations' among rodents, fleas and people to one where those interrelations required studies into population dynamics, endemicity and social organisation in order to mitigate pests and pestilence. This shift in Tanganyika anticipated later population ecology approaches on the African continent. Drawing on sources from the Tanzania National Archives, this article offers an important case study of the application of ecological frameworks in a colonial setting that anticipated later global scientific interest in studies of rodent populations and rodent-borne disease ecologies.

A single-dose F1-based mRNA-LNP vaccine provides protection against the lethal plague bacterium.

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 Yersinia pestis, 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 Y. pestis infection after a single dose. These data open avenues for urgently needed effective antibacterial vaccines.

Retrospective analysis of dissemination of the 2.MED1 phylogenetic branch of Yersinia pestis in the Caucasus.

The 2.MED1 phylogenetic branch of Yersinia pestis of the medieval biovar became widespread in the Caspian Sea region, the Caucasus, and the Northern Aral Sea region in the 20th century, causing outbreaks and epizootics of plague there. Some of the formed natural foci of 2.MED1 still show epizootic activity and retain their epidemic potential. In this work, we carried out a phylogenetic analysis of 46 Y. pestis strains of the medieval biovar isolated in the Caucasus, the Caspian Sea, and the Northern Aral Sea regions during epidemic outbreaks and epizootics from 1922-2014. The obtained phylogenetic data, together with epidemiological and epizootological data accumulated over a period of about a hundred years, indicate the presence of two waves of penetration of the 2.MED1 branch into the Caucasus. The first occurred, apparently, in the first half of the 20th century as a result of the penetration of 2.MED1 from the foci of the Northern and North-Western Caspian Sea. The second wave was caused by the spread of 2.MED1 from the Northern Aral to the foci of the North-Western, Northern and Eastern Caspian Sea regions at the beginning of the second half of the 20th century, followed by introduction into the Pre-Caucasus and Transcaucasia. The rapid spread of 2.MED1 could be associated with the transfer of the pathogen by land and sea transport in the process of economic activity of the population.

Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease.

ERAP2 is an aminopeptidase involved in immunological antigen presentation. Genotype data in human samples from before and after the Black Death, an epidemic due to Yersinia pestis, have marked changes in allele frequency of the single-nucleotide polymorphism (SNP) rs2549794, with the T allele suggested to be deleterious during this period, while ERAP2 is also implicated in autoimmune diseases. This study explored the association between variation at ERAP2 and (1) infection, (2) autoimmune disease, and (3) parental longevity. Genome-wide association studies (GWASs) of these outcomes were identified in contemporary cohorts (UK Biobank, FinnGen, and GenOMICC). Effect estimates were extracted for rs2549794 and rs2248374, a haplotype tagging SNP. Additionally, cis expression and protein quantitative trait loci (QTLs) for ERAP2 were used in Mendelian randomization (MR) analyses. Consistent with decreased survival in the Black Death, the T allele of rs2549794 showed evidence of association with respiratory infection (odds ratio; OR for pneumonia 1.03; 95% CI 1.01-1.05). Effect estimates were larger for more severe phenotypes (OR for critical care admission with pneumonia 1.08; 95% CI 1.02-1.14). In contrast, opposing effects were identified for Crohn disease (OR 0.86; 95% CI 0.82-0.90). This allele was shown to associate with decreased ERAP2 expression and protein levels, independent of haplotype. MR analyses suggest that ERAP2 expression may be mediating disease associations. Decreased ERAP2 expression is associated with severe respiratory infection with an opposing association with autoimmune diseases. These data support the hypothesis of balancing selection at this locus driven by autoimmune and infectious disease.

Design, synthesis and screening of herbicidal activity for new phenyl pyrazole-based protoporphyrinogen oxidase-inhibitors (PPO) overcoming resistance issues.

BACKGROUND: Whilst there are several methods to control weeds, which continuously plague farmers around the globe, the application of small molecular compounds is still the most effective technology to date. Plants can evolve to become resistant to PPO-inhibitors, a class of herbicides in commercial use since the 1960s. It is therefore essential to continuously develop new herbicides based on this mode-of-action with enhanced intrinsic activity, an improved resistance profile and favourable physicochemical properties. Based on an Amaranthus PPO crystal structure and subsequent modelling studies, halogen-substituted pyrazoles have been investigated as isosteres of uracil-based PPO-inhibitors. RESULTS: By combining structural features from the commercial PPO-inhibitors tiafenacil and pyraflufen-ethyl and by investigating receptor-binding properties, we identified new promising pyrazole-based lead structures showing strong activity in vitro and in vivo against economically important weeds of the Amaranthus genus: A. retroflexus, and resistant A. palmeri and A. tuberculatus. CONCLUSION: The present work covers a series of novel PPO-inhibiting compounds that contain a pyrazole ring and a substituted thioacetic acid sidechain attached to the core phenyl group. These compounds show good receptor fit in line with excellent herbicidal activity against weeds that plague corn and rice crops with low application rates. This, in combination with promising selectivity in corn, have the potential to mitigate and affect weeds that have become resistant to some of the current market standards. Remarkably, some of the novel PPO-inhibitors outlined herein show efficacies against economically important weeds that were superior to recently commercialized and structurally related tiafenacil. © 2023 Society of Chemical Industry.

Emergence, continuity, and evolution of Yersinia pestis throughout medieval and early modern Denmark.

The historical epidemiology of plague is controversial due to the scarcity and ambiguity of available data.1,2 A common source of debate is the extent and pattern of plague re-emergence and local continuity in Europe during the 14th-18th century CE.3 Despite having a uniquely long history of plague (∼5,000 years), Scandinavia is relatively underrepresented in the historical archives.4,5 To better understand the historical epidemiology and evolutionary history of plague in this region, we performed in-depth (n = 298) longitudinal screening (800 years) for the plague bacterium Yersinia pestis (Y. pestis) across 13 archaeological sites in Denmark from 1000 to 1800 CE. Our genomic and phylogenetic data captured the emergence, continuity, and evolution of Y. pestis in this region over a period of 300 years (14th-17th century CE), for which the plague-positivity rate was 8.3% (3.3%-14.3% by site). Our phylogenetic analysis revealed that the Danish Y. pestis sequences were interspersed with those from other European countries, rather than forming a single cluster, indicative of the generation, spread, and replacement of bacterial variants through communities rather than their long-term local persistence. These results provide an epidemiological link between Y. pestis and the unknown pestilence that afflicted medieval and early modern Europe. They also demonstrate how population-scale genomic evidence can be used to test hypotheses on disease mortality and epidemiology and help pave the way for the next generation of historical disease research.

Yersinia pestis Δail Mutants Are Not Susceptible to Human Complement Bactericidal Activity in the Flea.

Ail confers serum resistance in humans and is a critical virulence factor of Y. pestis, the causative agent of plague. Here, the contribution of Ail for Y. pestis survival in the flea vector was examined. Rat or human but not mouse sera were bactericidal against a Y. pestis Δail mutant at 28°C in vitro. Complement components deposited rapidly on the Y. pestis surface as measured by immunofluorescent microscopy. Ail reduced the amount of active C3b on the Y. pestis surface. Human sera retained bactericidal activity against a Y. pestis Δail mutant in the presence of mouse sera. However, in the flea vector, the serum protective properties of Ail were not required. Flea colonization studies using murine sera and Y. pestis KIM6+ wild type, a Δail mutant, and the Δail/ail+ control showed no differences in bacterial prevalence or numbers during the early stage of flea colonization. Similarly, flea studies with human blood showed Ail was not required for serum resistance. Finally, a variant of Ail (AilF100V E108_S109insS) from a human serum-sensitive Y. pestis subsp. microtus bv. Caucasica 1146 conferred resistance to human complement when expressed in the Y. pestis KIM6+ Δail mutant. This indicated that Ail activity was somehow blocked, most likely by lipooligosaccharide, in this serum sensitive strain. IMPORTANCE This work contributes to our understanding of how highly virulent Y. pestis evolved from its innocuous enteric predecessor. Among identified virulence factors is the attachment invasion locus protein, Ail, that is required to protect Y. pestis from serum complement in all mammals tested except mice. Murine sera is not bactericidal. In this study, we asked, is bactericidal sera from humans active in Y. pestis colonized fleas? We found it was not. The importance of this observation is that it identifies a protective niche for the growth of serum sensitive and nonsensitive Y. pestis strains.

Islamic Civilizations and Plagues: The Role of Religion, Faith and Psychology During Pandemics.

The current study seeks to analyze Muslim experiences of communicative diseases with a focus on the psychosocial impacts and public, communal, and personal responses of Muslim populations throughout history. By examining a selection of plague outbreaks between the 8-19th centuries across the lands broadly defined as the Islamic Mediterranean (Varlik, 2017), the guidelines and coping mechanisms that Muslims extracted from their traditional sources are highlighted. This historical perspective contributes to a better understanding of the psychological and social aspects of pandemics for the Muslim community, specifically for the role played by faith and spirituality as determinants of psychological well-being in Muslims' perceptions and responses. We suggest that such an understanding is especially useful for contemporary mental health practitioners working with Muslim patients through the global COVID-19 pandemic.