Genomic Identification of Multidrug-Resistant Salmonella Virchow Monophasic Variant Causing Human Septic Arthritis

Abstract

The monophasic variant of Salmonella Typhimurium has emerged and increased rapidly worldwide during the past two decades. The loss of genes encoding the second-phase flagella and the acquirement of the multi-drug resistance cassette are the main genomic characteristics of the S. Typhimurium monophasic variant. In this study, two Salmonella strains were isolated from the knee effusion and feces of a 4-year-old girl who presented with a case of septic arthritis and fever, respectively. Primary serovar identification did not detect the second-phase flagellar antigens of the strains using the classical slide agglutination test. Whole-genome sequencing analysis was performed to reveal that the replacement of the fljAB operon by a 4.8-kb cassette from E. coli caused the non-expression of phase-2 flagellar antigens of the strains, which were confirmed to be a novel S. Virchow monophasic variant (Salmonella 6,7,14:r:-) by core-genome multi-locus sequence typing (cgMLST). Compared to the 16 published S. Virchow genomes, the two strains shared a unique CRISPR type of VCT12, and showed a close genetic relationship to S. Virchow BCW_2814 and BCW_2815 strains, isolated from Denmark and China, respectively, based on cgMLST and CRISPR typing. Additionally, the acquisition of Salmonella genomic island 2 (SGI2) with an antimicrobial resistance gene cassette enabled the strains to be multidrug-resistant to chloramphenicol, tetracycline, trimethoprim, and sulfamethoxazole. The emergence of the multidrug-resistant S. Virchow monophasic variant revealed that whole-genome sequencing and CRISPR typing could be applied to identify the serovaraints of Salmonella enterica strains in the national Salmonella surveillance system.

Generation and microevolution of Salmonella 4,[5],12:i:- from Salmonella enterica serovar Typhimurium by complicated transpositions

“…A recent study also reported that other Salmonella serovars with the deletion of the second-phage flagellin-encoding gene cassette caused severe clinical infections in humans, e.g. the S. Virchow monophasic variant [26]. Therefore, the correlation between the loss of the fljAB region in Salmonella 4, [5],12:i:-and immune evasion, bacterial survival in niche environments or hosts and virulence needs to be further evaluated in S.…”

Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis

“…Septic arthritis recurred in 38% of patients treated with systemic antibiotics and/or surgical intervention, with higher rates of treatment failure among patients with MRSA-induced infection (Salgado et al, 2007). Despite antibiotic treatment, patients with septic arthritis develop sequelae such as secondary osteomyelitis, mono-articular arthritis, limb length discrepancy, or joint fusion (Vincent & Amirault, 1990;Wang et al, 2003). Numerous studies have suggested that septic arthritis recurrence may be attributable to the ability of S. aureus to penetrate eukaryotic host cells, thus limiting the efficacy of antibiotics that primarily act within the extracellular space (Alder et al, 2020;Yu et al, 2020;Cahill et al, 2021;Kwon et al, 2021).…”