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

## TL;DR

A new strain of Salmonella is causing milder symptoms in children but is more resistant to antibiotics, likely due to specific genetic traits.

## Contribution

Identifies the 'low-inflammation, high-resistance' evolutionary strategy of S.1,4,[5],12:i:- and links it to gogB and IncHI2/IncHI2A.

## Key findings

- Children infected with S.1,4,[5],12:i:- had lower C-reactive protein levels and hospitalization rates compared to traditional S. typhimurium.
- S.1,4,[5],12:i:- showed higher antibiotic resistance, especially to ceftriaxone, due to the IncHI2/IncHI2A plasmid.
- The gogB gene is present in 95.08% of S.1,4,[5],12:i:- strains, contributing to anti-inflammatory properties.

## Abstract

Salmonella enterica serovar 1,4,[5],12:i:-
(S.1,4,[5],12:i:-), a monophasic variant of
Salmonella typhimurium (S.
typhimurium), 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, S.1,4,[5],12:i:- has often been misclassified as
S. typhimurium. This study collected clinical data from
122 children infected with S.1,4,[5],12:i:- and 42 with
traditional S. typhimurium 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
S.1,4,[5],12:i:- infection were aged between 1 month and 2
years. Compared with traditional S. typhimurium, children
with S.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 vs. 33.94 mg/L, P <
0.05) and a lower hospitalization rate (26.23% vs. 42.86%,
P < 0.05). These differences may be attributed
to the high carriage rate of the anti-inflammatory gene
gogB in S.1,4,[5],12:i:- (95.08%
vs. 16.67%, P < 0.0001).
Additionally, S.1,4,[5],12:i:- exhibited a higher
resistance rate to multiple antibiotics, particularly ceftriaxone, than
traditional S. typhimurium (32.79% vs.
7.14%, P < 0.001). This increased resistance may be
associated with the carriage of the IncHI2/IncHI2A plasmid. The
S.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.

S.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 S. typhimurium
in pediatric infections. Crucially, we identified its unique
“low-inflammation, high-resistance” evolutionary strategy
associated with anti-inflammatory gene gogB 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.