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Yersinia pestis has caused at least three human plague pandemics. The second (Black Death, 14–17th centuries) and third (19–20th centuries) have been genetically characterised, but there is only a limited understanding of the first pandemic, the Plague of Justinian (6–8th centuries). To address this gap, we sequenced and analysed draft genomes of Y pestis obtained from two individuals who died in the first pandemic. Teeth were removed from two individuals (known as A120 and A76) from the early medieval Aschheim-Bajuwarenring cemetery (Aschheim, Bavaria, Germany). We isolated DNA from the teeth using a modified phenol-chloroform method. We screened DNA extracts for the presence of the Y pestis-specific pla gene on the pPCP1 plasmid using primers and standards from an established assay, enriched the DNA, and then sequenced it. We reconstructed draft genomes of the infectious Y pestis strains, compared them with a database of genomes from 131 Y pestis strains from the second and third pandemics, and constructed a maximum likelihood phylogenetic tree. Radiocarbon dating of both individuals (A120 to 533 AD [plus or minus 98 years]; A76 to 504 AD [plus or minus 61 years]) places them in the timeframe of the first pandemic. Our phylogeny contains a novel branch (100% bootstrap at all relevant nodes) leading to the two Justinian samples. This branch has no known contemporary representatives, and thus is either extinct or unsampled in wild rodent reservoirs. The Justinian branch is interleaved between two extant groups, 0.ANT1 and 0.ANT2, and is distant from strains associated with the second and third pandemics. We conclude that the Y pestis lineages that caused the Plague of Justinian and the Black Death 800 years later were independent emergences from rodents into human beings. These results show that rodent species worldwide represent important reservoirs for the repeated emergence of diverse lineages of Y pestis into human populations. McMaster University, Northern Arizona University, Social Sciences and Humanities Research Council of Canada, Canada Research Chairs Program, US Department of Homeland Security, US National Institutes of Health, Australian National Health and Medical Research Council.

Background Leptospirosis is a major zoonotic disease with widespread distribution and a large impact on human health. Carrier animals excrete pathogenic Leptospira primarily in their urine. Infection occurs when the pathogen enters a host through mucosa or small skin abrasions. Humans and other animals are exposed to the pathogen by direct contact with urine, contaminated soil or water. While many factors influence environmental cycling and the transmission of Leptospira to humans, the load of pathogenic Leptospira in the environment is likely to play a major role. Peridomestic rats are often implicated as a potential source of human disease; however exposure to other animals is a risk factor as well. The aim of this report is to highlight the importance of various carrier animals in terms of the quantity of Leptospira shed into the environment. For this, we performed a systematic literature review and a meta-analysis of the amount of pathogen that various animal species shed in their urine. Results The quantity of pathogen has been reported for cows, deer, dogs, humans, mice, and rats, in a total of 14 research articles. We estimated the average Leptospira per unit volume shed by each animal species, and the daily environmental contribution by considering the total volume of urine excreted by each carrier animal. Rats excrete the highest quantity of Leptospira per millilitre of urine (median = 5.7 × 10 6  cells), but large mammals excrete much more urine and thus shed significantly more Leptospira per day (5.1 × 10 8 to 1.3 × 10 9  cells). Conclusions Here we illustrate how, in a low-income rural Ecuadorian community, host population demographics, and prevalence of Leptospira infection can be integrated with estimates of shed Leptospira to suggest that peridomestic cattle may be more important than rats in environmental cycling and ultimately, transmission to humans.

Staphylococcus aureus is an important clinical pathogen worldwide and understanding this organism's phylogeny and, in particular, the role of recombination, is important both to understand the overall spread of virulent lineages and to characterize outbreaks. To further elucidate the phylogeny of S. aureus, 35 diverse strains were sequenced using whole genome sequencing. In addition, 29 publicly available whole genome sequences were included to create a single nucleotide polymorphism (SNP)-based phylogenetic tree encompassing 11 distinct lineages. All strains of a particular sequence type fell into the same clade with clear groupings of the major clonal complexes of CC8, CC5, CC30, CC45 and CC1. Using a novel analysis method, we plotted the homoplasy density and SNP density across the whole genome and found evidence of recombination throughout the entire chromosome, but when we examined individual clonal lineages we found very little recombination. However, when we analyzed three branches of multiple lineages, we saw intermediate and differing levels of recombination between them. These data demonstrate that in S. aureus, recombination occurs across major lineages that subsequently expand in a clonal manner. Estimated mutation rates for the CC8 and CC5 lineages were different from each other. While the CC8 lineage rate was similar to previous studies, the CC5 lineage was 100-fold greater. Fifty known virulence genes were screened in all genomes in silico to determine their distribution across major clades. Thirty-three genes were present variably across clades, most of which were not constrained by ancestry, indicating horizontal gene transfer or gene loss.

Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates ( n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCC mec ) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCC mec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production. IMPORTANCE Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production. Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.

In the twenty-first century, ticks and tick-borne diseases have expanded their ranges and impact across the US. With this spread, it has become vital to monitor vector and disease distributions, as these shifts have public health implications. Typically, tick-borne disease surveillance (e.g., Lyme disease) is passive and relies on case reports, while disease risk is calculated using active surveillance, where researchers collect ticks from the environment. Case reports provide the basis for estimating the number of cases; however, they provide minimal information on vector population or pathogen dynamics. Active surveillance monitors ticks and sylvatic pathogens at local scales, but it is resource-intensive. As a result, data are often sparse and aggregated across time and space to increase statistical power to model or identify range changes. Engaging public participation in surveillance efforts allows spatially and temporally diverse samples to be collected with minimal effort. These citizen-driven tick collections have the potential to provide a powerful tool for tracking vector and pathogen changes. We used MaxEnt species distribution models to predict the current and future distribution of Ixodes pacificus across the Western US through the use of a nationwide citizen science tick collection program. Here, we present niche models produced through citizen science tick collections over two years. Despite obvious limitations with citizen science collections, the models are consistent with previously-predicted species ranges in California that utilized more than thirty years of traditional surveillance data. Additionally, citizen science allows for an expanded understanding of I . pacificus distribution in Oregon and Washington. With the potential for rapid environmental changes instigated by a burgeoning human population and rapid climate change, the development of tools, concepts, and methodologies that provide rapid, current, and accurate assessment of important ecological qualities will be invaluable for monitoring and predicting disease across time and space.

In this study we examined changes to the human gut microbiome resulting from an eight-week intervention of either cardiorespiratory exercise (CRE) or resistance training exercise (RTE). Twenty-eight subjects (21 F; aged 18–26) were recruited for our CRE study and 28 subjects (17 F; aged 18–33) were recruited for our RTE study. Fecal samples for gut microbiome profiling were collected twice weekly during the pre-intervention phase (three weeks), intervention phase (eight weeks), and post-intervention phase (three weeks). Pre/post VO2max, three repetition maximum (3RM), and body composition measurements were conducted. Heart rate ranges for CRE were determined by subjects’ initial VO2max test. RTE weight ranges were established by subjects’ initial 3RM testing for squat, bench press, and bent-over row. Gut microbiota were profiled using 16S rRNA gene sequencing. Microbiome sequence data were analyzed with QIIME 2. CRE resulted in initial changes to the gut microbiome which were not sustained through or after the intervention period, while RTE resulted in no detectable changes to the gut microbiota. For both CRE and RTE, we observe some evidence that the baseline microbiome composition may be predictive of exercise gains. This work suggests that the human gut microbiome can change in response to a new exercise program, but the type of exercise likely impacts whether a change occurs. The changes observed in our CRE intervention resemble a disturbance to the microbiome, where an initial shift is observed followed by a return to the baseline state. More work is needed to understand how sustained changes to the microbiome occur, resulting in differences that have been reported in cross sectional studies of athletes and non-athletes.

Lipopolysaccharide (LPS) phase variation is a critical aspect of virulence in many Gram-negative bacteria. It is of particular importance to Coxiella burnetii , the biothreat pathogen that causes Q fever, as in vitro propagation of this organism leads to LPS truncation, which is associated with an attenuated and exempted from select agent status (Nine Mile II, NMII). Here, we demonstrate that NMII was recovered from the spleens of infected guinea pigs. Moreover, these strains exhibit a previously unrecognized form of elongated LPS and display increased virulence in comparison with the initial NMII strain. The reversion of a 3-bp mutation in the gene cbu0533 directly leads to LPS elongation. To address potential safety concerns, we introduce a modified NMII strain unable to produce elongated LPS. In vitro propagation of the pathogenic bacterium Coxiella burnetii , the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

Leptospirosis causes significant economic losses and is an occupational risk in the swine industry, especially in developing tropical regions where social and geoclimatic conditions are favorable for the transmission of this disease. Although vaccination can reduce infection risk, efficacy is diminished if local genetic and antigenic variants of the pathogen are not accounted for in the vaccine. Identifying and characterizing strains hosts, and potential mechanisms of transmission is therefore critical for public health mitigation practices. Our study was conducted on a rural breeding farm in Ecuador, where we used a PCR assay that targets lipL32 to detect Leptospira spp. and targeted gene sequencing to identify Leptospira santarosai in the kidneys, testicles, and ejaculate of a vaccinated boar. MAT results showed low titers against serovars found in the vaccine, but the MAT panel did not include serovars of L. santarosai. The boar showed no symptoms of leptospirosis but did show blood in the semen. However, no postmortem histopathological lesions were observed tissue samples. Vaccinated sows that were artificially inseminated with the semen from this boar had reproductive problems, suggesting that transmission had occurred. This is the first documented case of Leptospira santarosai in the reproductive tract of a boar. As L. santarosai is pathogenic in other livestock species and humans, our finding highlights the need to evaluate the prevalence and epidemiological significance of this pathogen in livestock and consider the possibility of venereal transmission. In addition, further studies are needed to identify and characterize local serovars that may impact diagnosis and vaccination programs to better control leptospirosis in livestock and spillover into the human population.

Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. We sampled dogs from five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 7 serogroups were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16S rRNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n = 7), santarosai (n = 7), and interrogans (n = 1). The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Asymptomatic carriage of Staphylococcus aureus is a major risk factor for subsequent clinical infection. Diminishing returns from mitigation efforts emphasize the need to better understand colonization, spread, and transmission of this opportunistic pathogen. While contact with other people presents opportunities for pathogen exposure and transmission, diversity of social connections may be protective against pathogens such as the common cold. This study examined whether social relationship resources, including the amount and diversity of social contacts, are associated with S. aureus colonization. Participants were community members (N = 443; 68% Hispanic) in naturally occurring social groups in southwestern Arizona. Four types of social relationships and loneliness were assessed, and samples from the skin, nose and throat were obtained to ascertain S. aureus colonization. Overall S. aureus prevalence was 64.8%. Neither the amount nor the diversity of social contacts were associated with S. aureus colonization. The concurrent validity of the social relationship assessments was supported by their moderate intercorrelations and by their positive association with self-rated health. The results suggest that the association of social network diversity and susceptibility to the common cold does not extend to S. aureus colonization. Conversely, colonization prevalence was not higher among those with more social contacts. The latter pattern suggests that social transmission may be relatively infrequent or that more intimate forms of social interaction may drive transmission and colonization resulting in high community prevalence of S. aureus colonization. These data inform communicable disease control efforts.