Abstract
Salmonella enterica serover Typhimurium definitive phage type DT104, resistant to multiple antibiotics, is one of the most widespread Salmonella species in human infection worldwide. Although several cohort studies indicate that DT104 carrying the multidrug resistance (MDR) locus on salmonella genomic island 1 is a possible hyper-virulent strain compared to DT104 strains without MDR, or other Salmonella enterica serotypes, existing experimental evidence regarding virulence properties associated with the MDR region is controversial. To address this question, we constructed an isogenic MDR deletion (∆MDR) mutant strain of DT104, SNS12, by allelic exchange and used Caenorhabditis elegans as a host model to assess differences in virulence between these two strains. SNS12 exhibited decreased virulence in C. elegans, and we observed increased colonization and proliferation of the intestine of C. elegans by DT104. The immune response against MDR-carrying DT104 appears to function through a non-canonical Unfolded Protein Response (UPR) pathway, namely prion-like-(QN-rich)-domain-bearing protein pathway (PQN), in a ced-1 dependent manner in C. elegans. Further, we also demonstrate that genes of the PQN pathway and antimicrobial peptide gene abf-2, are expressed at higher transcriptional levels in worms immediately following exposure to DT104, in comparison with worms exposed to SNS12. Altogether, our results suggest that the MDR region of Salmonella Typhimurium DT104 has a direct role in virulence against Caenorhabditis elegans.
Highlights
Non-typhoid Salmonella enterica is one of the primary causes of food-borne illness throughout the world [1]
The results clearly indicate that DT104 is resistant to ampicillin, amoxicillin, chloramphenicol, streptomycin, sulphamethoxazole, and tetracycline, but the isogenic ΔMDR mutant, SNS12, was resistant only to kanamycin, a result of introduction of the kanamycin resistance gene via allelic exchange (Table 2, Figure S1)
Synchronized L4 stage C. elegans worms fed with either wild type DT104 or SNS12 exhibited a significant shortened lifespan (P
Summary
Non-typhoid Salmonella enterica is one of the primary causes of food-borne illness throughout the world [1]. Salmonella enterica serovar Typhimurium definitive phage type DT104 (hereafter, DT104) [3], first isolated in the 1960s, emerged in the 1990s as many isolates of this strain were found to have acquired multidrug resistance, to ampicillin, chloramphenicol, streptomycin, sulfonamides and tetracycline (ACSSuT) [4]. The multidrug resistance (MDR) region of DT104 is localized to a 13 kb segment of SGI1 [3,5,6]. Several cohort studies have indicated that DT104 carrying the MDR region is a hypervirulent strain, as compared to DT104 strains without MDR or other Salmonella enterica serotypes [7,8]. Insertional inactivation of the MDR locus in DT104 was reported to reduce virulence in chickens when compared with the isogenic parent strain [12]
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