In a recent study published within the journal PNAS, researchers investigated how large-scale livestock rearing may end in the emergence and transmission of novel, potentially zoonotic pathogens. They combined multiple lines of evidence from molecular dating, comparative genomic analyses, and phylogeography to look at how the rearing of pigs allowed for novel Streptococcus suis lineages, a few of that are able to zoonotic spillover. Their findings reveal how pathogens, including S. suis, adapt to use substantial changes of their host population sizes and the way this, in turn, can not directly contribute to the emergence of novel, potentially pandemic-scale, and zoonotic, highly pathogenic strains of hitherto benign microbes.
Study: The emergence and diversification of a zoonotic pathogen from inside the microbiota of intensively farmed pigs. Image Credit: Dusan Petkovic / Shutterstock
Livestock rearing and its effects on pathogens
Over the past few centuries, the human population explosion and its associated need for livestock as food and labor to assist within the agricultural industry has resulted in the worldwide upscaling of livestock rearing. The agricultural feedback loop of intensive farming systems enables larger livestock populations, which in turn demands increased crop production. This has resulted in livestock populations now exceeding the combined populations of humans and wild animals.
These practices, together with the long-distance transport of reared animals, have contributed to low-genetic diversity and high-density livestock. This presents an excellent recipe for outbreaks of pathogens able to wiping out thousands and thousands of livestock without the genetic capability for resistance, which, when transported, can infect not only other livestock populations but additionally wild populations of the identical or similar species.
Alarmingly, this cocktail of events is hypothesized to advertise the emergence of novel zoonotic pathogens, arising from pathogens jumping to latest hosts and mutations in previously benign microbiota previously related to reared animals.
“This path to pathogen emergence could also be particularly necessary in intensive farming systems, where large population size and high population density may select for traits related to pathogenicity, while biosecurity reduces the chance of novel pathogens entering the population.”
Streptococcus suis is a ubiquitous microbiota component of the upper respiratory tract of pigs. Previously benign, intensive rearing of pigs within the 19th and 20th centuries, the microbe has been observed to adapt to a more pathogenic lifestyle. In 1954, the bacteria was implicated in widespread disease in pigs, and today presents one of the common ailments in piglets. Alarmingly, gathered mutations have allowed the bacteria to zoonotically spill over to humans, related to meningitis, arthritis, endocarditis, and septicemia, with sudden death in each human and porcine hosts.
Following the primary human S. suis-associated mortality in 1968, the bacteria has since led to large outbreaks in China and presents certainly one of the leading causes of adult septicemia and meningitis across Southeast Asia.
“Difficulties in identifying the determinants of pathogenicity in S. suis have been attributed to its complex pathogenesis and high level of genetic diversity. Few studies have considered virulence aspects in strains aside from ST 1, which is accountable for most cases of S. suis disease in each pigs and humans worldwide.”
Concerning the study
In the current study, researchers investigated the associations between intensive pig rearing, the emergence of novel S. suis lineages, and their potential for zoonotic spillover. They conducted a population genomic evaluation of over 3,000 bacterial samples derived from tonsil and nasal swabs from pigs and wild boar. They moreover collected infected blood from humans and pigs affected by S. suis disease across North America, Europe, Asia, and Australia. They aimed to elucidate the emergence, geographic spread, and degree of diversification of pathogenic lineages of the bacteria.
The study dataset comprised 3,070 genomic isolates of S. suis samples derived from previously existing published data and picked up and sequenced as a component of this project. This included 29 published reference genomes and collection isolates from 15 countries spread across the five continents above. Sampling was conducted between 2014 and 2018. Isolates were processed through the Illunima whole genome HiSeq 25000 sequencing pipeline, which was then used to construct a genomic library of isolates. Raw sequences were quality-checked, cleaned, and used to generate de novo assemblies for polymorphism evaluations.
The pipeline described by Athey et al. was used for serotyping and sequencing-typing analyses. Generated genomes were subsequently annotated to discover homologous genes and analyze pathogenicity-associated genomic islands. The PopPunk software was then used to discover divergent genomes and classify them into lineages. The six commonest lineages thus identified were tested for temporal signals using a regression of root-to-tip distances against the yr of isolate sampling. Finally, ancestral state reconstructions were used to infer the geographic spread of identified lineages.
Dates of emergence and paths of between-country transmission for the six commonest pathogenic lineages. (A) Estimates of the dates of essentially the most recent common ancestors of the six commonest pathogenic lineages (coloured points) against an estimate of the worldwide variety of pigs (gray line). The vertical dashed line shows the date of the primary reported case of S. suis disease in pigs (1954), and the dotted line shows the primary reported human case (1968). (B) Map showing inferred routes of transmission of those six pathogenic lineages between the countries in our collection. Arrows represent routes with no less than one inferred transmission event. Routes with greater than ten inferred transmission events are shown in red, those with greater than three in blue, and people with one to a few in turquoise.
Study findings
Study findings revealed that over the past 200 years, rearing porcine populations have increased by over 200-fold, with the utmost increase throughout the latter half of the 20th century. These increases have resulted within the admittedly gradual yet concerning emergence of over 10 lineages with highly pathogenic life histories. The high density of reared pigs, normally antibiotic-treated, has led to diverse, antibiotic-resistance lineages of S. suis presenting significant control challenges.
Analyses of samples from Spain reveal that pigs, each reared and wild boar, are hosts to S. suis strains which are highly genetically diverse, suggesting that the association between the microbe and its host has been long-standing. Genetic dating analyses, nevertheless, revealed that each one of the six commonest pathogenic S. suis strains emerged throughout the 19th and 20th centuries, corresponding with the unprecedented increase in host rearing.
“The conclusion that these dates reflect an ecological shift toward pathogenicity in no less than a few of these lineages is supported by evidence that they coincided with the acquisition of a pathogenicity-associated genomic island (Island 3). It’s further supported by patterns of genome reduction in each of the pathogenic lineages. In comparisons across bacterial species, it has been shown that bacterial pathogenicity is broadly related to smaller genomes and fewer genes.”
Analyses of the metabolic capacities of pathogenic lineages revealed that no less than two identified genomic islands had significantly upped their capabilities for within-host growth, with all six islands depicting increased metabolic activities over their more benign counterparts. In other bacteria studies, each within-host growth and metabolic rate have been linked to increased virulence, suggesting a trend in S. suis adapting to a more virulent life history with greater potential for zoonotic spillover.
“Pathogenic lineages could also be higher able to use particular regions of the tonsil than commensal lineages and vice versa, thereby reducing within-host competition. This could lead on to segregation of those populations and reduced gene flow between them, which could in turn result in the genome reduction in additional pathogenic lineages as a consequence of fewer opportunities for gene acquisition from more diverse commensal lineages.”
Finally, analyses revealed that current S. suis strains depict a high rate of spread, able to rapidly infecting a whole farm of pigs with the addition of 1 or a number of infected individuals. The massive-scale transport of livestock thereby presents an extra problem: previous endemic virulent strains being transmitted across nations and even continents, able to infecting novel host populations with little to no innate resistance against them.
“Our results provide a framework for understanding the genomic diversity in S. suis and its association with pathogenicity. That is prone to be of widespread use in S. suis research and in informing strategies for controlling the burden of this disease on pig farming and human health. As our collection spans only a small proportion of the countries that farm pigs globally, further sampling from a broader range countries and more extensive sampling inside countries, particularly those with large and growing pig populations, is required to analyze the existence of additional pathogenic lineages which are geographically restricted or have recently emerged.”