EsaD, a Secretion Factor for the Ess Pathway inStaphylococcus aureus

Abstract

Staphylococcus aureus encodes the Sec-independent Ess secretion pathway, an ortholog of mycobacterial T7 secretion systems which is required for the virulence of this Gram-positive microbe. The Ess (ESX secretion) pathway was previously defined as a genomic cluster of eight genes, esxA, esaA, essA, essB, esaB, essC, esaC, and esxB. essABC encode membrane proteins involved in the stable expression of esxA, esxB, and esaC, genes specifying three secreted polypeptide substrates. esaB, which encodes a small cytoplasmic protein, represses the synthesis of EsaC but not that of EsxA and EsxB. Here we investigated a hitherto uncharacterized gene, esaD, located downstream of esxB. Expression of esaD is activated by mutations in esaB and essB. EsaD, the 617-amino-acid product of esaD, is positioned in the membrane and is also accessible to EsaD-specific antibodies on the bacterial surface. S. aureus mutants lacking esaD are defective in the secretion of EsxA. Following intravenous inoculation of mice, S. aureus esaD mutants generate fewer abscesses with a reduced bacterial load compared to wild-type parent strain Newman. The chromosomes of Listeria and Bacillus species with Ess pathways also harbor esaD homologues downstream of esxB, suggesting that the contributory role of EsaD in Ess secretion may be shared among Gram-positive pathogens.

EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection

“…The average load of S. aureus USA300 per gram of kidney tissues was 7.9 log 10 CFU, and it was 7.4 log 10 CFU for the isogenic ΔessE mutant (Fig. 6B) (P ϭ 0.0024), a reduction similar to that observed for other mutant alleles of the ESS cluster (15,18). Immunohistochemical analysis of thin-sectioned tissue was used to assess the abundance of anti-F4/80-positive macrophages and of RANTES production in renal abscess lesions.…”

“…Earlier work reported that mutations in genes for substrates of ESS secretion (esxB, esxC, or esxD) resulted in defects of S. aureus essD expression (17,18). The Esx secretion defect for mutants with defects in other ess genes had also been attributed to the loss of essD expression (17).…”

Comparative genome analysis of Streptococcus iniae DX09 reveals new insights into niche adaptation and competitive host colonisation ability

“…T7SS was initially described and termed the 'ESX protein secretion system' in pathogenic mycobacteria [23] belonging to the class Actinobacteria with high GC content. Subsequently, a related secretion system (ESS protein secretion) was detected in some Firmicutes bacteria, including Staphylococcus aureus [24][25][26][27][28][29], Listeria monocytogenes [21,30], Bacillus subtilis [21,30] and Streptococcus agalactiae [21,30]. We have identified an ESS secretion system in S. iniae, which also belongs to the low-GC Firmicutes bacterial group.…”

“…Previous investigations have demonstrated a crucial role of T7SS in bacterial survival within the host [21,23,31,32], consistent with transmission electron micrographs of interactions between S. iniae DX09 and spleen cells from diseased catfish. Moreover, considerable evidence is available supporting essential roles of the actinobacterial ESS protein secretion system in virulence [26][27][28][29].…”

“…A complete nucleotide sequence-based pangenome was created from nine genomes (Table 1) with Gegenees and subsequently used as a reference for comparison with nine other S. iniae genomes (Table 1) using the BLAST Ring Image Generator (BRIG) 28 ( Figure 2A). The data revealed extremely high conservation amongst the lineages, with mobile genetic elements accounting for the majority of differences.…”