Salmonella enterica serovar Typhimurium is a bacterial pathogen that can cause gastroenteritis in humans and, in some cases, life-threatening systemic infections. Recently, in various geographic settings, these bacteria have acquired genetic elements from other organisms or the environment, allowing them to survive traditional antibiotic treatments. A concerning trend is emerging in North America’s public health landscape: The rise of Salmonella Typhimurium strains belonging to the sequence type 213 (ST213). This sequence type is quietly becoming more prevalent across the continent. New research has revealed how this pathogen has evolved, warning us about its potential to become a significant health concern, particularly due to its increasing antibiotic resistance and unique survival strategies.
The diverse Salmonella Typhimurium family
The Typhimurium serovar is highly diverse, comprising various sequence types (STs) that have evolved from ST19, considered the parental sequence type. Each ST is associated with distinct genetic traits that contribute to its adaptability and public health impact. Among these, ST34 has emerged as a pandemic clone that gained global attention due to its widespread dissemination and ability to cause gastrointestinal infections. Its success has been partially attributed to its multidrug resistance profile and ability to adapt to multiple hosts.
Similarly, ST313 has become notorious for its role in severe bloodstream infections, particularly affecting immunocompromised individuals in Africa, and it has been suggested that these bacteria are evolving to be human-adapted. These examples highlight the dynamic nature of Salmonella Typhimurium and set the stage for understanding ST213, which is rapidly gaining attention for its unique genomic features and ability to cause systemic and enteric infections in North America.
A tale of two variants
While variation within serovars has long been recognized, recent research has unveiled fascinating diversity at the intra-sequence type level. The ST213 sequence type provides a compelling example of this phenomenon, presenting what could be described as a microbiological case of ‘split personality’. At first glance, European strains (EU-ST213) and North American strains (NA-ST213) appear to be close relatives, sharing the same sequence type classification. However, deeper genomic analysis has revealed significant differences in their genetic makeup.
For example, while EU-ST213 strains maintain a relatively antibiotic-susceptible profile, their North American counterparts have evolved into largely multidrug-resistant variants. This dramatic divergence suggests that these strains may share their sequence type classification more by coincidence than genuine evolutionary divergence. Intriguingly, NA-ST213 shows a closer evolutionary relationship to the pandemic ST34 strains than to its European ST equivalents, raising concerns about its potential to emerge as a similarly successful pathogen across the region.
What makes NA-ST213 unique?
The NA-ST213 strains share interesting similarities with the ST34 isolates while also displaying distinctive characteristics. This unique profile reflects both the traits they have lost and those they have gained through evolution.
A different genetic tool kit
While most Salmonella Typhimurium strains carry well-characterised virulence factors, NA-ST213 has taken its own unique path. Like ST34, it lacks the traditional virulence plasmid (pSTV) (a small circular DNA molecule, present in the bacterium, distinct from its own DNA) and its associated genes that typically help the bacteria to cause infection. Additionally, it’s missing other genes, traditionally considered important for colonization in the host. However, these apparent losses have not diminished its pathogenic potential. Instead, NA-ST213 has acquired a diverse collection of other genes, though their role in virulence remains to be fully understood.
Antimicrobial resistance profile
Perhaps most concerning is NA-ST213’s extensive repertoire of drug-resistance genes, primarily carried on IncC plasmids. These genetic elements harbor the blaCMY-2 gene, conferring resistance to third-generation cephalosporins, critical antibiotics used to treat severe infections. The picture becomes even more complex when considering that many strains, particularly those isolated from human infections, carry additional resistance genes against quinolones and trimethoprim. This multi-drug resistance profile distinguishes NA-ST213 from its European counterparts and mirrors the troubling trend seen in other successful pathogens.
A sophisticated infection strategy
Another distinctive characteristic of NA-ST213 is its unique strategy for infecting host cells. Although it shows lower adhesion and invasion rates in cultured human cells compared to ST19 reference strains, once inside, it replicates at an impressively high rate. This “stealth” approach may help the bacteria evade the host’s immune defenses while still sustaining substantial infection levels. Interestingly, this behavior resembles the invasive tendencies of ST313 and the human-restricted pathogen Salmonella Typhi, hinting at a possible evolutionary convergence in how these strains have adapted their infection strategies.
Environmental adaptability
Additionally, these strains can form biofilms, a trait that provides an advantage for survival in adverse environmental conditions. Whether in food processing plants, hospital settings or agricultural water sources, this ability allows the bacteria to persist in diverse settings, opening multiple routes for transmission. Infections could spread through contaminated food, water, or even animal contact, highlighting the deep interconnection between our health and the world around us. To effectively combat Salmonella like NA-ST213, we need to think beyond human health and take a holistic One Health approach that also considers the well-being of animals and the environment.
A modern success story: Exploring the transmission and pathogenicity of NA-ST213
The success of NA-ST213 strains appears to be linked to the acquisition of IncC plasmids, which first emerged in Mexico between 2002 and 2006. NA-ST213 strains carrying these plasmids have since spread throughout North America, likely because the genetic content of these plasmids provides the bacteria a significant survival advantage in environments where antibiotic use is common, whether in healthcare settings, livestock farms, or even the broader environment.
Constant exposure to antibiotics could be a key factor driving the spread of these lineages, allowing them to thrive where other strains struggle. Unfortunately, gaps in geospatial and clinical data make it challenging to map the precise transmission patterns of NA-ST213. However, one thing is clear: The acquisition of these plasmids has played a relevant role in the rise and spread of NA-ST213, offering a striking example of how antibiotic resistance can fuel the success of bacterial lineages.
What role does plasmids play in the success of certain bacterial lineages, such as Salmonella Typhimurium NA-ST213? The acquisition of these plasmids has played a relevant role in the rise and spread of NA-ST213, offering a striking example of how antibiotic resistance can fuel the success of bacterial lineages.
Isela Serrano Fujarte
Moreover, these plasmids carry more than just antimicrobial resistance genes, with at least one-third of their genetic content having unknown functions. This raises important questions about the potential role these plasmids have played in shaping the evolutionary success of NA-ST213.
Credit. Author
Public health implications
The emergence of NA-ST213 presents a complex challenge for public health systems. Its multi-drug resistance profile significantly narrows treatment options for infected individuals, which is particularly concerning given its ability to cause both gastrointestinal and invasive infections. Perhaps most troubling is how NA-ST213’s success demonstrates Salmonella’s remarkable ability to adapt and thrive using different strategies, even without the traditional virulence factors we typically associate with harmful bacteria. This adaptability suggests that current approaches to pathogen surveillance and control may need to be reevaluated in order to effectively combat these emerging threats.
The path ahead: Integrative strategies for managing evolving bacterial risks
The emergence of NA-ST213, alongside ST34 and ST313, represents more than just the appearance of new bacterial variants; it is a paradigm shift in our understanding of bacterial pathogenesis and evolution. These sequence types serve as a reminder that bacterial threats are not static but dynamically evolving entities capable of rapid adaptation to new environments and challenges. The success of these strains, particularly NA-ST213, challenges traditional notions of virulence.
Despite lacking conventional virulence factors, these bacteria have been associated with systemic infections in otherwise healthy individuals. This shows the need for a more integrative approach to assessing bacterial threats, one that looks beyond the presence or absence of specific genes and considers the holistic behavior of each pathogen across different environments, rather than relying on a one-size-fits-all approach.
Lastly, the rapid dissemination of these sequence types across vast geographical areas serves as a wake-up call for public health systems worldwide. It points out the need for more comprehensive, real-time surveillance programs capable of quickly identifying and tracking emerging threats. Furthermore, it highlights the importance of international collaboration in addressing what are truly global health challenges.
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Journal reference
Serrano-Fujarte, I., Calva, E., García-Domínguez, J., Ortiz-Jiménez, S., & Puente, J. L. (2024). Population structure and ongoing microevolution of the emerging multidrug-resistant Salmonella Typhimurium ST213. npj Antimicrobials and Resistance, 2(1), 10. https://doi.org/10.1038/s44259-024-00027-6
