Evolutionary adaptations of a pediatric pathogen: low-inflammatory and high-resistance phenotypes in the emerging <i>Salmonella typhimurium</i> monophasic variant 1,4,[5],12:i:-

<i>Salmonella enterica</i> serovar 1,4,[5],12:i:- (<i>S</i>.1,4,[5],12:i:-), a monophasic variant of <i>Salmonella typhimurium</i> (<i>S. typhimurium</i>), is an emerging multidrug-resistant pathogen posing a significant threat to pediatric health. Research on this variant remains limited, and due to challenges associated with traditional identification methods, <i>S</i>.1,4,[5],12:i:- has often been misclassified as <i>S. typhimurium</i>. This study collected clinical data from 122 children infected with <i>S</i>.1,4,[5],12:i:- and 42 with traditional <i>S. typhimurium</i> in Fujian Province, China, between 2014 and 2023. Whole-genome sequencing was used for strain analysis. Our findings revealed that 77.87% of children with <i>S</i>.1,4,[5],12:i:- infection were aged between 1 month and 2 years. Compared with traditional <i>S. typhimurium</i>, children with <i>S</i>.1,4,[5],12:i:- exhibited milder clinical symptoms, as evidenced by lower levels of the inflammatory marker C-reactive protein (16.53 mg/L <i>vs</i>. 33.94 mg/L, <i>P</i> < 0.05) and a lower hospitalization rate (26.23% <i>vs</i>. 42.86%, <i>P</i> < 0.05). These differences may be attributed to the high carriage rate of the anti-inflammatory gene <i>gogB</i> in <i>S</i>.1,4,[5],12:i:- (95.08% <i>vs</i>. 16.67%, <i>P</i> < 0.0001). Additionally, <i>S</i>.1,4,[5],12:i:- exhibited a higher resistance rate to multiple antibiotics, particularly ceftriaxone, than traditional <i>S. typhimurium</i> (32.79% <i>vs</i>. 7.14%, <i>P</i> < 0.001). This increased resistance may be associated with the carriage of the IncHI2/IncHI2A plasmid. The <i>S</i>.1,4,[5],12:i:- ST34 clone prevalent in this region aligns with the global epidemic trend but exhibits greater genetic diversity. Overall, the stealthy evolutionary adaptation of low-inflammation and high-resistance provides novel insights into this variant's global dominance. These findings underscore the importance of heightened clinical awareness and targeted interventions, particularly for vulnerable pediatric populations. IMPORTANCE <i>S</i>.1,4,[5],12:i:- poses a growing global health threat, particularly endangering infants and young children. Characterized by increasing prevalence, multidrug resistance, and diagnostic challenges, this variant demonstrates milder inflammatory responses yet stronger antibiotic resistance than traditional <i>S. typhimurium</i> in pediatric infections. Crucially, we identified its unique "low-inflammation, high-resistance" evolutionary strategy associated with anti-inflammatory gene <i>gogB</i> and resistance plasmid IncHI2/IncHI2A. The stealthy evolutionary adaptation provides novel insights into this variant's global dominance, while offering critical guidance for improving clinical management and formulating targeted public health measures to protect vulnerable pediatric populations against this cunning pathogen.