Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

The human lineage entered a more carnivorous niche 2.6 mya. A range of evidence indicates this increased zoonotic pathogen pressure. This evidence includes increased zoonotic infections modern hunter-gatherers and bushmeat hunters relative to others living in the same environments, exceptionally low stomach pH compared to other primates, human-specific downregulation in ANTXR2 that would have protected against increased exposure to zoonotic anthrax, exceptional human immune responses to LPS compared to other primates, and other divergent immune genes. These all point to change, and likely intensification, in the disease environment of Homo compared to earlier hominins and other apes. At the same time, the brain, an organ in which inflammatory immune responses are highly constrained, begins to increase, eventually tripling in size. We propose that the combination of increased zoonotic pathogen pressure and the challenges of defending a large brain and body from pathogens across what would eventually become the longest lifespan of any mammal, selected for intensification of the self-medication strategies already in place in apes and other primates, resulting in a variety of plant-based pathogen defenses. In support, there is evidence of medicinal plant use by hominins in the middle Paleolithic, and all cultures today have sophisticated, plant-based medical systems, incorporate plant components high in secondary compounds (spices) into food, and regularly consume psychoactive substances that are harmful to helminths and other pathogens in the CNS and other tissues. The computational challenges of discovering effective plant-based treatments, and the economic challenges of benefiting from costly-to- acquire medical knowledge that would be more often useful to others than oneself, were selection pressures for increased cognitive abilities and unique exchange relationships in Homo. In the story of human evolution, which has long featured hunters, shamans and healers had an equal role to play.

Clinical and Epidemiological Characteristics of Streptococcus suis Infections in Catalonia, Spain

Introduction:Streptococcus suis (S. suis) is a human zoonotic pathogen of occupational origin, with infection acquired through contact with live pigs or pig meat. Pig farming is one of Catalonia's biggest industries and as a result this region of Spain has one of the highest density pig populations per km2. The aim of our study was to describe the infections caused by S. suis occurring in that area over a 9-year period.Materials and Methods: A retrospective, multi-center study was carried out by searching records from 15 hospitals in Catalonia for the period between 2010 and 2019.Results: Over the study period altogether nine cases of S. suis infection were identified in five hospitals, with five of these cases occurring in the 2018–2019 period. The mean age of patients was 48 ± 8.9 years and all of them were males. Five patients (55.6%) worked in pig farms. The most frequent manifestation of infection was meningitis (5 cases; 55.6%) followed by septic arthritis (3 cases; 33.3%). None of the patients died at 30 days; nonetheless, 4 developed hearing loss as a long-term complication.Conclusion: The most commonly identified S. suis infection was meningitis. Over 50% of the episodes occurred in the last 2 years and have affected pig farm workers. Further surveillance is needed in order to know its prevalence.

Hfq Regulates Efflux Pump Expression and Purine Metabolic Pathway to Increase Trimethoprim Resistance in Aeromonas veronii

Aeromonas veronii (A. veronii) is a zoonotic pathogen. It causes clinically a variety of diseases such as dysentery, bacteremia, and meningitis, and brings huge losses to aquaculture. A. veronii has been documented as a multiple antibiotic resistant bacterium. Hfq (host factor for RNA bacteriophage Qβ replication) participates in the regulations of the virulence, adhesion, and nitrogen fixation, effecting on the growth, metabolism synthesis and stress resistance in bacteria. The deletion of hfq gene in A. veronii showed more sensitivity to trimethoprim, accompanying by the upregulations of purine metabolic genes and downregulations of efflux pump genes by transcriptomic data analysis. Coherently, the complementation of efflux pump-related genes acrA and acrB recovered the trimethoprim resistance in Δhfq. Besides, the accumulations of adenosine and guanosine were increased in Δhfq in metabonomic data. The strain Δhfq conferred more sensitive to trimethoprim after appending 1 mM guanosine to M9 medium, while wild type was not altered. These results demonstrated that Hfq mediated trimethoprim resistance by elevating efflux pump expression and degrading adenosine, and guanosine metabolites. Collectively, Hfq is a potential target to tackle trimethoprim resistance in A. veronii infection.

An Update on Zoonotic Cryptosporidium Species and Genotypes in Humans

The enteric parasite, Cryptosporidium is a major cause of diarrhoeal illness in humans and animals worldwide. No effective therapeutics or vaccines are available and therefore control is dependent on understanding transmission dynamics. The development of molecular detection and typing tools has resulted in the identification of a large number of cryptic species and genotypes and facilitated our understanding of their potential for zoonotic transmission. Of the 44 recognised Cryptosporidium species and >120 genotypes, 19 species, and four genotypes have been reported in humans with C. hominis, C. parvum, C. meleagridis, C. canis and C. felis being the most prevalent. The development of typing tools that are still lacking some zoonotic species and genotypes and more extensive molecular epidemiological studies in countries where the potential for transmission is highest are required to further our understanding of this important zoonotic pathogen. Similarly, whole-genome sequencing (WGS) and amplicon next-generation sequencing (NGS) are important for more accurately tracking transmission and understanding the mechanisms behind host specificity.

Mutation rate dynamics reflect ecological change in an emerging zoonotic pathogen

Mutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study, we investigate two factors that are predicted to influence the mutation rate: ecology and genome size. We conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogen Streptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact that ecology can have on the adaptive potential of bacterial pathogens.

Fatal Streptococcus iniae Infection in a Juvenile Free-Ranging Short-Beaked Common Dolphin (Delphinus delphis)

Streptococcus iniae (S. iniae) is a significant aquatic pathogen of farmed fish species, important zoonotic pathogen, and reported cause of disease in captive Amazon River dolphins (Inia geoffrensis) and a bottlenose dolphin (Tursiops truncatus). Here we report S. iniae as the cause of subcutaneous abscesses, sepsis and mortality in a juvenile free-ranging short-beaked common dolphin (Delphinus delphis) found deceased on a metropolitan Australian beach. Body surfaces were covered by multifocal, depressed, deep, irregular cutaneous ulcerations, which microscopically were characterised by ruptured subcutaneous abscesses with intralesional cocci. Routine microbiological investigations revealed a heavy growth of beta-haemolytic Streptococcus sp. identified as Streptococcus iniae in skin lesions as well as from heart blood, the latter supportive of sepsis. Tissues were negative for cetacean morbillivirus and no other disease processes were identified. S. iniae has not been reported in free-ranging marine mammals, nor in Australian delphinids, previously. More notably a pathogen of captive animals, this case report identifies S. iniae as a pathogen of wild dolphins also. In addition to expanding the host reservoir of a significant zoonotic pathogen, determining the source of infection as well as possible consequences for other marine mammals and wild and intensive fish stocks warrants further investigations.

Structure, receptor recognition and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein

The recent isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. Here, we determined cryo-electron microscopy structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and identified that it binds canine, feline and porcine aminopeptidase N (APN encoded by ANPEP) orthologs which serve as entry receptors. Introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry, suggesting that single nucleotide polymorphisms could account for the detection of this virus in some individuals. Human polyclonal plasma antibodies elicited by HCoV-229E infection and a porcine coronavirus monoclonal antibody inhibit CCoV-HuPn-2018 S-mediated entry, indicating elicitation of cross-neutralizing activity among α-coronaviruses. These data provide a blueprint of the CCoV-HuPn-2018 infection machinery, unveil the viral entry receptor and pave the way for vaccine and therapeutic development targeting this zoonotic pathogen.