The Salmonella virulence plasmid spv genes are required for cytopathology in human monocyte-derived macrophages

Abstract

SummaryThe pathogenesis of serious systemic Salmonella infections is characterized by survival and proliferation of bacteria inside macrophages. Infection of human monocyte-derived macrophages in vitro with S. typhimurium or S. dublin produces cytopathology characterized by detachment of cells that contain large numbers of proliferating bacteria. This cytopathology is dependent on the expression of the bacterial spv genes, a virulence locus previously shown to markedly enhance the ability of Salmonella to produce systemic disease. After 24 h of infection, macrophage cultures contain two populations of bacteria: (i) proliferating organisms present in a detached cell fraction; and (ii) a static bacterial population in macrophages remaining attached to the culture well. Mutations in either the essential transcriptional activator SpvR or the key SpvB protein markedly reduce the cytopathic effect of Salmonella infection. The spvdependent cytopathology in macrophages exhibits characteristics of apoptosis, with release of nucleosomes into the cytoplasm, nuclear condensation and DNA fragmentation. The current ®ndings suggest that the mechanism of the spv effect is through induction of increased cytopathology in host macrophages.

Salmonella enterica serovar Typhi plasmid pRST98 enhances caspase-3 mediated macrophage apoptosis by suppressing nitric oxide production

“…Additionally, we find an interesting phenomenon that the percentage of apoptosis between macrophages infected with ST8, ST8-ΔpR ST98 and ST8-c-pR ST98 was not significantly difference at early phase, and that the cytotoxicity of pR ST98 occurred later. Similar phenomenon of delayed cytotoxicity of virulent effectors was observed by Libby et al (2000) in assaying the spv phenotype in macrophages and Paesold et al (2002) in intestinal epithelial cells. Perhaps, the delayed cytotoxicity of pR ST98 caused S. typhi infection.…”

“…In 2005, we identified Salmonella plasmid virulence (spv) homologous genes which were considered to be absent from S. typhi before identifying it on pR ST98 by Southern blot and DNA sequence analysis (Huang et al, 2005). Spv genes have been shown to be required for Salmonella intracellular growth and systemic infection (Libby et al, 2000).…”

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

“…However, delayed macrophage death becomes apparent 18-24 h postinfection. This form of cell death (i) requires T3SS2 and the effectors SpvB and SseL, (ii) is mediated by caspase-1, and (iii) results in production of IL-1β, DNA cleavage, cell lysis, and inflammation [85][86][87][88]. Interestingly, during this form of delayed macrophage death, Salmonella activates two inflammasome receptors, NLRP3 and NLRC4 [89].…”

“…SpvB inhibits the formation of vacuole-associated actin polymerizations (VAPs) in HeLa cells [312] and negatively regulates the formation of SIFs [313]. The ADP-ribosylation activity of SpvB is also required for a delayed form of cell death that is observed in host cells 18-24 h after infection with noninvasive bacteria or T3SS1 mutants [67,85,314,315]. One report showed that SpvB could be secreted into a culture medium mimicking the intracellular iron concentrations of eukaryotic cells in a T3SS-independent manner [316].…”

Detection of virulence genes in Salmonella Enteritidis isolated from different sources

“…The virulence of Salmonella is linked to a combination of chromosomal and plasmid factors, the chromosomally located invasion gene invA being thought to trigger the invasion of salmonellae into cultured epithelial cells (1), while an operon (spvRABCD), containing five genes, is present on plasmids commonly associated with some serotypes, the spv genes possibly having the ability to increase the severity of enteritis and allow infection and persistence at extraintestinal sites (3).…”