Abstract
The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05–1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20–1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03–1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27–0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17–5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia.
Highlights
The accessory gene regulator locus of Staphylococcus aureus is a quorum-sensing virulence regulator
Invasive S. aureus infection is still associated with high mortality and morbidity, and recent studies have shown that the mortality rates of S. aureus bacteraemia (SAB) are 20–30%, even though antibiotic therapies are advanced[1,2,3,4,5]
We investigated the association between dysfunctional agr and 30-day mortality of invasive S. aureus infection by sites of infections for the five most common infection sites: centralline-associated bloodstream infection (CLABSI), pneumonia, skin and soft tissue infection (SSTI), bone and joint infection (BJI) and endocarditis (Supplementary Table 2)
Summary
The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. The dysfunction of the agr locus can cause the strain to form abundant biofilms and become deficient in autolysis even though the bacterial density is high These changes can contribute to the persistence of the infection by hindering the host immune system. Many clinical studies have reported the influence of dysfunctional agr on the courses of invasive S. aureus infection, and some studies have shown that dysfunctional agr may be related to unfavourable outcomes such as persistent bacteraemia and a high mortality r ate[7,29,30,31,32]. No study that systematically reviews and quantitatively analyses the studies concerning the association between agr dysfunction and clinical outcomes has been performed so far
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