Comparative Analysis of Virulence and Toxin Expression of Vancomycin-Intermediate and Vancomycin-Sensitive Staphylococcus aureus Strains

Abstract

Previous studies on vancomycin-intermediate Staphylococcus aureus (VISA) have mainly focused on drug resistance, the evolution of differences in virulence between VISA and vancomycin-sensitive S. aureus (VSSA) requires further investigation. To address this issue, in this study, we compared the virulence and toxin profiles of pair groups of VISA and VSSA strains, including a series of vancomycin-resistant induced S. aureus strains-SA0534, SA0534-V8, and SA0534-V16. We established a mouse skin infection model to evaluate the invasive capacity of VISA strains, and found that although mice infected with VISA had smaller-sized abscesses than those infected with VSSA, the abscesses persisted for a longer period (up to 9 days). Infection with VISA strains was associated with a lower mortality rate in Galleria mellonella larvae compared to infection with VSSA strains (≥ 40% vs. ≤ 3% survival at 28 h). Additionally, VISA were more effective in colonizing the nasal passage of mice than VSSA, and in vitro experiments showed that while VISA strains were less virulent they showed enhanced intracellular survival compared to VSSA strains. RNA sequencing of VISA strains revealed significant differences in the expression levels of the agr, hla, cap, spa, clfB, and sbi genes and suggested that platelet activation is only weakly induced by VISA. Collectively, our findings indicate that VISA is less virulent than VSSA but has a greater capacity to colonize human hosts and evade destruction by the host innate immune system, resulting in persistent and chronic S. aureus infection.

Prevalence of Vancomycin Resistance among Clinical Isolates of MRSA from Different Governorates in Egypt

“…A previous study by El-sayed et al estimated similar result that VRSA isolates harbored the highest percent of icaA and icaD genes 28 . However, Jin et al reported that VISA isolates had higher biofilm formation capacity encoded by biofilm encoding genes 37 .…”

Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature

“…For this, we used the Galleria mellonella larvae infection model (Fig. 4g), which has been widely used to study microbial pathogenesis/virulence, including that of S. aureus [27][28][29][30] . Comparative analysis was performed between isolates belonging to groups III (10 out of 27 isolates) and V (13 out of 13 isolates), and a subset of isolates that included S. aureus USA300 and six isolates presenting phenotypes similar to USA300 in vitro, i.e., high replication, and high host cell death (selected from groups IVa, IVb, IVc; Fig.…”

Vancomycin Resistance in Enterococcus and Staphylococcus aureus

“…Despite the greater therapeutic difficulty in treating VISA infections, VISA appears to be less virulent than VSSA but with a greater ability to colonise and evade the host immune system [ 460 , 461 ]. Prior studies employing a mouse model of skin and soft tissue infection demonstrated that VISA had a much lower invasive capacity than VSSA; VISA also induced lower levels of innate immunity in persistent and chronic infections [ 461 ]. Proposed mechanisms for VISA’s virulence reduction include loss-of-activity mutations or dysfunction of the quorum-sensing, virulence regulator system agr [ 461 ].…”

“…Prior studies employing a mouse model of skin and soft tissue infection demonstrated that VISA had a much lower invasive capacity than VSSA; VISA also induced lower levels of innate immunity in persistent and chronic infections [ 461 ]. Proposed mechanisms for VISA’s virulence reduction include loss-of-activity mutations or dysfunction of the quorum-sensing, virulence regulator system agr [ 461 ]. Virulence factors under agr control include expression of the α-hemolysin encoded by hla [ 462 ], with mutant or dysfunctional agr VISA isolates found to produce up to 20-fold less α-toxin than VSSA and also less lethal in an in vivo murine bacteraemia model [ 460 ].…”

“…In addition, VISA had a comparatively higher capacity for biofilm formation than VISA, which are key contributors to S. aureus immune evasion and persistence. This was supported by the upregulation fnbB and sdrCDE genes which are associated with cell adhesion and immune evasion respectively [ 461 ].…”