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Background: Salmonella enterica subsp. enterica serovar I 4,[5],12:i:- (antigenic formula: 1,4,[5],12:i:-) is a variant of Salmonella Typhimurium (O:4 (B) serogroup). S. I 4,[5],12:i:- is a monophasic serovar that lacks the second flagellar antigen (i.e., antigen 1,2 in serovar Typhimurium). One of the earliest documented S. I 4,[5],12:i:- isolates in Europe, as reported in peer-reviewed literature, was recovered from a chicken carcass in Portugal during 1986/87. This serovar emerged as a common serovar after 1990’s. S. I 4,[5],12:i:- ranked as the sixth most frequent Salmonella serotype associated with human illness in the United States in 2006. Similarly, it was the fourth most common serotype identified in human isolates in Spain in 1998.

NCBI PD link for serovar I 4,[5],12:i:-: https://www.ncbi.nlm.nih.gov/pathogens/isolates/#(taxgroup_name:%22Salmonella%20enterica%22)%20AND%20computed_types:(%22serotype=I%204,%5B5%5D,12:i:-%22)

Genetic characteristics: Serovar I 4,[5],12:i:- has been found to be polyphyletic with four lineages identified and one stand-alone singleton that does not cluster with any other Salmonella I 4,[5],12:i:- isolates. S. Typhimurium, with RR3 inserted into the hin-iroB site, serves as a key intermediate. Through IS26/IS1R-mediated transposition of RR3-S. Typhimurium, the monophasic variant Salmonella 4,[5],12:i:- was emerged. Through analyzing a total of 13,612 serovar I 4,[5],12:i:- genomes available in the NCBI PD database, Trachsel et al. found that genomes of Salmonella serovar I 4,[5],12:i:- strains were distributed across 30 countries across five continents (North America, Europe, Asia, Oceania, and South America), with the majority originating from the United States (59%) and the United Kingdom (28%). The metal tolerance island SGI-4 was identified in 71% of these sequences, while the R-type ASSuT was found in 55%. Notably, 65% of the sequences were multidrug-resistant (MDR), aligning with the fact that serovar I 4,[5],12:i:- is the most common MDR serovar. Swine-associated strain sequences (the most prevalent among food-animal sources) were also significantly more likely to carry SGI-4 and MDR genes compared to sequences from other animal-associated isolates. A Chinese study revealed that all 45 S. 4,[5],12:i:- strains analyzed belonged to sequence type ST34, which was further categorized into two distinct ribosomal STs and nine core-genome STs. In one strain, the colistin resistance gene mcr-1 and the extended-spectrum beta-lactamase (ESBL) gene blaCTXbla_CTX-M-14 were found to be co-located on the chromosome. The study highlighted that dynamic changes in antimicrobial resistance regions, the transferability of IncHI2 plasmids, and the chromosomal integration of resistance genes contributed to the diversity of antimicrobial resistance profiles observed in S. 4,[5],12:i:-. Another Chinese research found that MDR I 4,[5],12:i:- isolates showed a high rate of carrying virulence genes including invA, sseL, mgtC, siiE, sopB, gipA, gtgB, sspH1, and sspH2 (72.4%~98.9%). By screening 108 S. 4,5,12:i:- isolates from various sources in Thailand and four international S. 4,5,12:i:- isolates, Win et al. found a total of 21 phenotypic AMR patterns with the predominant AmpST resistant phenotype [i.e., 84% (or 94 of 112) tested positive for resistance to ampicillin, streptomycin, and tetracycline], and 89% (or 100 of 112) were identified to be MDR. Two clones with different gene deletions were identified, one in the US and one in Europe.

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