Microbiology, Public Health and the Murals of Diego Rivera.

Diego Rivera, an acclaimed Mexican painter active during the first half of the twentieth century, painted multiple frescoes in Mexico and the United States. Some include depictions of bacteria, their interactions with human hosts, and processes related to microbiology and public health including the microbial origin of life, diagnosis of infection, vaccine production and immunization. Microbiological subjects in Rivera's murals at the Mexican Ministry of Health in Mexico City; the Detroit Institute of Art, Detroit; Rockefeller Center, New York/Palacio de Bellas Artes, Mexico City; Chapultepec Park, Mexico City; and the Institute of Social Security, Mexico City, span almost 25 years, from 1929 to 1953. Illustrating the successes of the application of microbiological discoveries and methods to public health and the prevention and treatment of infectious diseases, they benefited from Rivera's creativity in melding microbiology's unique technological and scientific aspects and public health elements with industrial and political components.

Misunderstandings and misinterpretations: Antimicrobial use and resistance in salmon aquaculture.

The exponential growth of aquaculture over the past 30 years has been accompanied by a parallel increase in the use of antimicrobials. This widespread use has had negative effects on animal, human and environmental health and affected the biodiversity of the environments where aquaculture takes place. Results showing these harmful effects have been resisted and made light of by the aquaculture industry and their scientific supporters through introduction of misunderstandings and misinterpretations of concepts developed in the evolution, genetics, and molecular epidemiology of antimicrobial resistance. We focus on a few of the most obvious scientific shortcomings and biases of two recent attempts to minimise the negative impacts of excessive antimicrobial use in Chilean salmon aquaculture on human and piscine health and on the environment. Such open debate is critical to timely implementation of effective regulation of antimicrobial usage in salmon aquaculture in Chile, if the negative local and worldwide impacts of this usage are to be avoided.

Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes.

The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. Autoimmunity, cross-reactivity, molecular mimicry, coinfections, and borrelial tolerance to antimicrobials/persistence have been hypothesized and studied as potential causes of PTLDS. Studies of borrelial tolerance/persistence in vitro in response to antimicrobials and experimental studies in mice and nonhuman primates, taken together with clinical reports, have revealed that B. burgdorferi becomes tolerant to antimicrobials and may sometimes persist in animals and humans after the currently recommended antimicrobial treatment. Moreover, B. burgdorferi is pleomorphic and can generate viable-but-nonculturable bacteria, states also involved in antimicrobial tolerance. The multiple regulatory pathways and structural genes involved in mediating this tolerance to antimicrobials and environmental stressors by persistence might include the stringent (rel and dksA) and host adaptation (rpoS) responses, sugar metabolism (glpD), and polypeptide transporters (opp). Application of this recently reported knowledge to clinical studies can be expected to clarify the potential role of bacterial antibacterial tolerance/persistence in Lyme disease and PTLDS.

Freshwater salmon aquaculture in Chile and transferable antimicrobial resistance.

Large amounts of antimicrobials are used in salmonid aquaculture in Chile. Most are used in marine aquaculture, but appreciable amounts are also employed in freshwater aquaculture. Much research and many publications have examined transferable antimicrobial resistance in bacteria isolated from marine salmon farms, but much less attention has been paid to this area in freshwater salmon farming. A recent paper by Domínguez et al. (2019) has as least in part remedied this situation. We now comment on some of its interpretations and have attempted to point out its areas of strength and weakness in light of the published scientific literature. Seen in this setting, the important results presented by Domínguez et al. (2019) underline the need for increased awareness of the challenge to animal and human health posed by excessive use of antimicrobials in aquaculture.

Diego Rivera, The History of Medicine in Mexico: Peopled Demand for Better Health, mural in 1953 still current.

Although public health and social medicine have a long history in Latin America going back to Co lonial times, their relevance has ebbed and flowed as a result of the development of a variety of social and political movements. The Mexican Revolution accelerated implementation of public health po licies in Mexico and resulted in the creation of the Mexican Institute of Social Security to serve the health and social security needs of the country's population. Construction of the Hospital La Raza and its embellishment by the mural paintings of Diego Rivera and David Alfaro Siqueiros correspon ded to the heyday of public health ideas in Mexico. This is clearly reflected in Rivera's mural painting from 1953, The History of Medicine in Mexico: People's Demand for Better Health. The left side of the painting, representing the history of modern medicine in Mexico, exemplifies the tensions between individuals and social groups demanding the fruits of modern medicine and public health, and en trenched bureaucracy and private interests resisting their demands. Rivera's artistry illustrates this tension by depicting urban social groups and a family with a pregnant mother and children reques ting medical attention on one side of the main panel, facing condescending physicians, bureaucrats and upper society gentlemen and ladies on the other side. The importance of social movements to the development of public health policies illustrated by Rivera in 1953 continues to be relevant in Latin America today where increasing millions still lack the benefits of health care and social security.

Diego Rivera, the history of medicine in Mexico: peopled demand for better health, mural in 1953 still current / Diego Rivera: la historia de la medicina en México: el pueblo en demanda de salud, mural de 1953 aún vigente

Abstract: Although public health and social medicine have a long history in Latin America going back to Co lonial times, their relevance has ebbed and flowed as a result of the development of a variety of social and political movements. The Mexican Revolution accelerated implementation of public health po licies in Mexico and resulted in the creation of the Mexican Institute of Social Security to serve the health and social security needs of the country's population. Construction of the Hospital La Raza and its embellishment by the mural paintings of Diego Rivera and David Alfaro Siqueiros correspon ded to the heyday of public health ideas in Mexico. This is clearly reflected in Rivera's mural painting from 1953, The History of Medicine in Mexico: People's Demand for Better Health. The left side of the painting, representing the history of modern medicine in Mexico, exemplifies the tensions between individuals and social groups demanding the fruits of modern medicine and public health, and en trenched bureaucracy and private interests resisting their demands. Rivera's artistry illustrates this tension by depicting urban social groups and a family with a pregnant mother and children reques ting medical attention on one side of the main panel, facing condescending physicians, bureaucrats and upper society gentlemen and ladies on the other side. The importance of social movements to the development of public health policies illustrated by Rivera in 1953 continues to be relevant in Latin America today where increasing millions still lack the benefits of health care and social security.

Antimicrobial resistance in Chile and The One Health paradigm: Dealing with threats to human and veterinary health resulting from antimicrobial use in salmon aquaculture and the clinic. / Resistencia a los antimicrobianos en Chile y el paradigma de Una Salud: manejando los riesgos para la salud pública humana y animal resultante del uso de antimicrobianos en la acuicultura del salmón y en medicina.

The emergence and dissemination of antimicrobial-resistant bacteria (ARB) is currently seen as one of the major threats to human and animal public health. Veterinary use of antimicrobials in both developing and developed countries is many-fold greater than their use in human medicine and is an important determinant in selection of ARB. In light of the recently outlined National Plan Against Antimicrobial Resistance in Chile, our findings on antimicrobial use in salmon aquaculture and their impact on the environment and human health are highly relevant. Ninety-five percent of tetracyclines, phenicols and quinolones imported into Chile between 1998 and 2015 were for veterinary use, mostly in salmon aquaculture. Excessive use of antimicrobials at aquaculture sites was associated with antimicrobial residues in marine sediments 8 km distant and the presence of resistant marine bacteria harboring easily transmissible resistance genes, in mobile genetic elements, to these same antimicrobials. Moreover, quinolone and integron resistance genes in human pathogens isolated from patients in coastal regions adjacent to aquaculture sites were identical to genes isolated from regional marine bacteria, consistent with genetic communication between bacteria in these different environments. Passage of antimicrobials into the marine environment can potentially diminish environmental diversity, contaminate wild fish for human consumption, and facilitate the appearance of harmful algal blooms and resistant zoonotic and human pathogens. Our findings suggest that changes in aquaculture in Chile that prevent fish infections and decrease antimicrobial usage will prove a determining factor in preventing human and animal infections with multiply-resistant ARB in accord with the modern paradigm of One Health.

El retablo de Isenheim: religión, arte y medicina / The Isenheim altarpiece: religion, art and medicine

Northern Europe at the beginning of the 16th Century was in turmoil as a result of religious and political dissention, epidemics of plague, syphilis, ergotism, and famine, and the threat of the Ottoman Empire. In Alsace, a fulcrum between Germany, France, Switzerland and the Netherlands, Grünewald painted his celebrated and complex altarpiece at Isenheim in a convent chapel of the Antonine religious order that kept a hospital for the care of patients suffering from ergotism, plague, syphilis and other illnesses. The ten paintings of this altarpiece convey a series of religious, medical and political meanings, with the scenes of the Crucifixion and the Resurrection being thought to play an integral part of the curative process. This was because patients could be soothed by comparing their suffering to that of Christ on the cross and could console themselves by the Resurrection. The portrait of Christ in the cross is astounding in its realism and naturalism. It represents, with great pathological veracity, a tortured body in agony, a break with previous traditional representations of this event. Impressive pathological detail is also given to a figure in the Temptation scene. The entire work is suffused with religious connotations provided by the composition, the forms and the richness and sophisticated use of colors. Although Grünewald's paintings are few and the facts of his personal life sparse, it is known he married a Jewish woman, supported the peasant revolts, and was probably a Lutheran in a Catholic area. While Grünewald is considered the epitome of a German artist, the universal projections of his art have influenced physicians and the artistic productions of many painters, writers, musicians and sculptors throughout the world.

Plasmid-Mediated Quinolone Resistance (PMQR) Genes and Class 1 Integrons in Quinolone-Resistant Marine Bacteria and Clinical Isolates of Escherichia coli from an Aquacultural Area.

Antimicrobial usage in aquaculture selects for antimicrobial-resistant microorganisms in the marine environment. The relevance of this selection to terrestrial animal and human health is unclear. Quinolone-resistance genes qnrA, qnrB, and qnrS were chromosomally located in four randomly chosen quinolone-resistant marine bacteria isolated from an aquacultural area with heavy quinolone usage. In quinolone-resistant uropathogenic clinical isolates of Escherichia coli from a coastal area bordering the same aquacultural region, qnrA was chromosomally located in two E. coli isolates, while qnrB and qnrS were located in small molecular weight plasmids in two other E. coli isolates. Three quinolone-resistant marine bacteria and three quinolone-resistant E. coli contained class 1 integrons but without physical association with PMQR genes. In both marine bacteria and uropathogenic E. coli, class 1 integrons had similar co-linear structures, identical gene cassettes, and similarities in their flanking regions. In a Marinobacter sp. marine isolate and in one E. coli clinical isolate, sequences immediately upstream of the qnrS gene were homologous to comparable sequences of numerous plasmid-located qnrS genes while downstream sequences were different. The observed commonality of quinolone resistance genes and integrons suggests that aquacultural use of antimicrobials might facilitate horizontal gene transfer between bacteria in diverse ecological locations.

[The Isenheim altarpiece: religion, art and medicine]. / El retablo de Isenheim: religión, arte y medicina.

Northern Europe at the beginning of the 16th Century was in turmoil as a result of religious and political dissention, epidemics of plague, syphilis, ergotism, and famine, and the threat of the Ottoman Empire. In Alsace, a fulcrum between Germany, France, Switzerland and the Netherlands, Grünewald painted his celebrated and complex altarpiece at Isenheim in a convent chapel of the Antonine religious order that kept a hospital for the care of patients suffering from ergotism, plague, syphilis and other illnesses. The ten paintings of this altarpiece convey a series of religious, medical and political meanings, with the scenes of the Crucifixion and the Resurrection being thought to play an integral part of the curative process. This was because patients could be soothed by comparing their suffering to that of Christ on the cross and could console themselves by the Resurrection. The portrait of Christ in the cross is astounding in its realism and naturalism. It represents, with great pathological veracity, a tortured body in agony, a break with previous traditional representations of this event. Impressive pathological detail is also given to a figure in the Temptation scene. The entire work is suffused with religious connotations provided by the composition, the forms and the richness and sophisticated use of colors. Although Grünewald's paintings are few and the facts of his personal life sparse, it is known he married a Jewish woman, supported the peasant revolts, and was probably a Lutheran in a Catholic area. While Grünewald is considered the epitome of a German artist, the universal projections of his art have influenced physicians and the artistic productions of many painters, writers, musicians and sculptors throughout the world.

Resistencia a los antimicrobianos en Chile y el paradigma de Una Salud: manejando los riesgos para la salud pública humana y animal resultante del uso de antimicrobianos en la acuicultura del salmón y en medicina / Antimicrobial resistance in Chile and The One Health paradigm: dealing with threats to human and veterinary health resulting from antimicrobial use in salmon aquaculture and the clinic

El aumento de la resistencia bacteriana múltiple a antimicrobianos es considerado una gran amenaza para la salud pública mundial y como generador de una importante crisis en el funcionamiento de los sistemas de salud. Esta crisis es discutida diariamente por los gobiernos y los parlamentos, las instituciones globales de salud, fundaciones benéficas y de científicos y de profesionales de la salud y también de consumidores de productos animales. En todos los países del orbe se ha identificado al uso de antimicrobianos en la crianza industrial de animales como un importante determinante en la selección de esta resistencia. Aprovechando la oportunidad que se ha planteado en Chile con el diseño del Plan Nacional Contra la Resistencia a los Antimicrobianos, hemos creído importante revisitar y actualizar sumariamente nuestros estudios sobre el uso de antimicrobianos en la acuicultura del salmón y de su potencial impacto en el ambiente y la salud humana y animal. Estos estudios indican que 95% de tres grupos de antimicrobianos importados al país, que incluyen tetraciclinas, fenicoles y quinolonas, son usados en medicina veterinaria y mayormente en la acuicultura del salmón. Nuestros estudios indican que el excesivo uso de estos antimicrobianos genera la presencia de residuos de antimicrobianos en el ambiente marino hasta 8 km de los sitios de acuicultura, los que seleccionan a bacterias con resistencia múltiple en dicho ambiente, ya que ellas contienen variados genes de resistencia a estos antimicrobianos. Estos genes de resistencia están contenidos en elementos genéticos móviles incluyendo plásmidos e integrones, los que son trasmitidos a otras bacterias permitiendo su potencial diseminación epidémica entre poblaciones bacterianas. Bacterias del ambiente marino contienen genes idénticos a los genes de resistencia a quinolonas e integrones similares a los de patógenos humanos, sugiriendo comunicación genética entre estas bacterias de diversos ambientes. Alrededor de los recintos de acuicultura, este uso exagerado de antimicrobianos contamina con ellos también a peces silvestres para consumo humano y potencialmente selecciona BRA en su carne y en los productos de acuicultura. El consumo de estos productos selecciona bacterias resistentes en el microbioma humano y facilita también el intercambio genético entre bacterias del ambiente acuático y la microbiota comensal y patógena humana. El pasaje de antimicrobianos al ambiente marino disminuye la diversidad en él, y potencialmente podría facilitar la aparición de florecimientos de algas nocivas, la infección de peces por patógenos piscícolas resistentes los antimicrobianos y la aparición de patógenos zoonóticos resistentes, incluyendo a Vibrio parahaemolyticus. Estos hallazgos sugieren que la prevención de infecciones en peces y la disminución del uso de antimicrobianos en su crianza, será en Chile un factor determinante en la prevención de infecciones humanas y animales con resistencia múltiple a los antimicrobianos, de acuerdo con el paradigma moderno e integral de Una Salud.

The emergence and dissemination of antimicrobial-resistant bacteria (ARB) is currently seen as one of the major threats to human and animal public health. Veterinary use of antimicrobials in both developing and developed countries is many-fold greater than their use in human medicine and is an important determinant in selection of ARB. In light of the recently outlined National Plan Against Antimicrobial Resistance in Chile, our findings on antimicrobial use in salmon aquaculture and their impact on the environment and human health are highly relevant. Ninety-five percent of tetracyclines, phenicols and quinolones imported into Chile between 1998 and 2015 were for veterinary use, mostly in salmon aquaculture. Excessive use of antimicrobials at aquaculture sites was associated with antimicrobial residues in marine sediments 8 km distant and the presence of resistant marine bacteria harboring easily transmissible resistance genes, in mobile genetic elements, to these same antimicrobials. Moreover, quinolone and integron resistance genes in human pathogens isolated from patients in coastal regions adjacent to aquaculture sites were identical to genes isolated from regional marine bacteria, consistent with genetic communication between bacteria in these different environments. Passage of antimicrobials into the marine environment can potentially diminish environmental diversity, contaminate wild fish for human consumption, and facilitate the appearance of harmful algal blooms and resistant zoonotic and human pathogens. Our findings suggest that changes in aquaculture in Chile that prevent fish infections and decrease antimicrobial usage will prove a determining factor in preventing human and animal infections with multiply-resistant ARB in accord with the modern paradigm of One Health.

Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle.

Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B. burgdorferi. It modulates the expression of identified and unidentified open reading frames needed to deal with and overcome the many nutritional stresses and other challenges faced by the spirochete in ticks and animal reservoirs. The metabolic and morphologic changes resulting from activation of the stringent response in B. burgdorferi may also be involved in the recently described non-genetic phenotypic phenomenon of tolerance to otherwise lethal doses of antimicrobials and to other antimicrobial activities. It may thus constitute a linchpin in multiple aspects of infections with Lyme disease borrelia, providing a link between the micro-ecological challenges of its enzootic life-cycle and long-term residence in the tissues of its animal reservoirs, with the evolutionary side effect of potential persistence in incidental human hosts.

Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance.

Aquaculture uses hundreds of tonnes of antimicrobials annually to prevent and treat bacterial infection. The passage of these antimicrobials into the aquatic environment selects for resistant bacteria and resistance genes and stimulates bacterial mutation, recombination, and horizontal gene transfer. The potential bridging of aquatic and human pathogen resistomes leads to emergence of new antimicrobial-resistant bacteria and global dissemination of them and their antimicrobial resistance genes into animal and human populations. Efforts to prevent antimicrobial overuse in aquaculture must include education of all stakeholders about its detrimental effects on the health of fish, human beings, and the aquatic ecosystem (the notion of One Health), and encouragement of environmentally friendly measures of disease prevention, including vaccines, probiotics, and bacteriophages. Adoption of these measures is a crucial supplement to efforts dealing with antimicrobial resistance by developing new therapeutic agents, if headway is to be made against the increasing problem of antimicrobial resistance in human and veterinary medicine.

Even therapeutic antimicrobial use in animal husbandry may generate environmental hazards to human health.

The potential negative impact for human health of veterinary use of antimicrobials in prophylaxis, metaphylaxis and growth promotion in animal husbandry was first established in the 1960s and 1970s. Determination of the molecular structure of antimicrobial resistance plasmids at that time explained the ability of antimicrobial resistance genes to disseminate among bacterial populations and elucidated the reasons for the negative effects of antimicrobials used in food animals for human health. In this issue of Environmental Microbiology, Liu et al. (2016) show that even therapeutic use of antimicrobials in dairy calves has an appreciable environmental microbiological footprint. We discuss the negative implications of this footprint for human health and the possibility they may lead to calls for increased regulation of veterinary antimicrobial use in terrestrial and aquatic environments.