Mobilome-driven partitions of the resistome in Salmonella

Abstract

Mobile genetic elements (MGEs) or mobilomes promote the mobilization and dissemination of antimicrobial resistance genes (ARGs), serving as critical drivers for antimicrobial resistance (AMR) accumulation, interaction, and persistence. However, systematic and quantitative evaluations of the role of mobilome in spreading resistome in a bacterial pathogen remain unaddressed, partially due to the lack of closed genomes. Here, we examined MGEs across 1,817 Salmonella isolates with complete genomic sequences from 58 countries between 1911 and 2022. We found the plasmid harboring 69.8% ARGs to be the largest ARG reservoir, correlated with serovar-based evolution in most Salmonella lineages. Prophages, specifically RCS47 and SJ46, play a crucial role in the plasmids’ plasticity and the acquisition of ARGs. Furthermore, distinct ARG accumulation, including resistance toward last-resort antibiotics, exhibited an MGE-favored manner. Certain socioeconomic and ecological factors, as additional layers of mediators, are associated with the preferential distribution of MGE-mediated ARGs in Salmonella . Collectively, this study demonstrated an uncharted knowledge of the segmentation of Salmonella resistome driven by mobilome, elucidating dynamic drivers and distinct mediators for resistome development that are of immediate relevance for targeted interventions. IMPORTANCE Antimicrobial resistance (AMR) has become a significant global challenge, with an estimated 10 million deaths annually by 2050. The emergence of AMR is mainly attributed to mobile genetic elements (MGEs or mobilomes), which accelerate wide dissemination among pathogens. The interaction between mobilomes and AMR genes (or resistomes) in Salmonella , a primary cause of diarrheal diseases that results in over 90 million cases annually, remains poorly understood. The available fragmented or incomplete genomes remain a significant limitation in investigating the relationship between AMR and MGEs. Here, we collected the most extensive closed Salmonella genomes ( n = 1,817) from various sources across 58 countries. Notably, our results demonstrate that resistome transmission between Salmonella lineages follows a specific pattern of MGEs and is influenced by external drivers, including certain socioeconomic factors. Therefore, targeted interventions are urgently needed to mitigate the catastrophic consequences of Salmonella AMR.

Genomic investigation and nationwide tracking of pediatric invasive nontyphoidal Salmonella in China

“…Foodborne outbreak cases of Salmonella Goldcoast were mainly reported in Europe before [12][13][14][15] ; however, they have been increasingly observed in both the Chinese mainland and Taiwan, China nowadays 16,17 . Considering an emerging Salmonella serovar associated with human infections in China, One Health scale genomic tracking for S. Goldcoast was performed.…”

A Retrospective Analysis of Salmonella Isolates across 11 Animal Species (1982–1999) Led to the First Identification of Chromosomally Encoded blaSCO-1 in the USA

“…The development of antimicrobial resistance (AMR) within Salmonella is attributed to various factors, including chromosomally encoded genes, chromosomal mutations, and the acquisition and recombination of mobile genetic elements such as transposons and plasmids [ 4 , 5 , 6 , 7 ]. For instance, Salmonella harbors naturally occurring chromosomally mediated β-lactamases, believed to have evolved from penicillin-binding proteins with shared sequence homology, and they have been disseminated by mobile genetic elements [ 8 , 9 ].…”

Climate change affects the spread of typhoid pathogens

“…Although the existing typhoid vaccine offers a protection rate of more than 80% and remains effective for up to 7 years (Milligan et al, 2018), the challenge lies in timely vaccine distribution in regions experiencing severe weather conditions, which is predicted to become more common. At the same time, S. Typhi is increasingly resistant to three widely prescribed front-line antimicrobials-chloramphenicol, co-trimoxazole and amoxicillin (Birger et al, 2022;Jia et al, 2023). This issue has been attributed to the expansion of antimicrobial use in response to increasing typhoid fever infection rates.Given the substantial risks to public health, here we elaborate on the potential effects of climate change on the dissemination of S. Typhi and highlight some appropriate interventions.…”

“…At the same time, S . Typhi is increasingly resistant to three widely prescribed front‐line antimicrobials—chloramphenicol, co‐trimoxazole and amoxicillin (Birger et al., 2022 ; Jia et al., 2023 ). This issue has been attributed to the expansion of antimicrobial use in response to increasing typhoid fever infection rates.…”