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.
Highlights
Staphylococcus aureus is a major multidrug−resistant opportunistic pathogen in healthcare settings that represents a significant public health burden (Deresinski, 2005)
The excessive use of vancomycin has led to the emergence of vancomycinintermediate S. aureus (VISA) and hVISA strains worldwide. hVISA/VISA strains have a thicker cell wall compared to vancomycin-sensitive S. aureus (VSSA) strains (Moreira et al, 1997; Boyle-Vavra et al, 2001), as well as lower autolytic activity (Dai et al, 2017) and altered cell wall-associated protein profile, growth rate, and Agr system function (Cui et al, 2003; Dai et al, 2017)
The G. mellonella infection model has been widely used to compare the virulence of VISA and VSSA (Peleg et al, 2009)
Summary
Staphylococcus aureus is a major multidrug−resistant opportunistic pathogen in healthcare settings that represents a significant public health burden (Deresinski, 2005). Acquisition of the mecA gene encoding penicillin-binding protein 2 conferring methicillin resistance (Kobayashi et al, 2002) has led to the emergence of methicillin-resistant S. aureus (MRSA), which is responsible for thousands of infections annually and contributes to the growing problem of hospital-acquired (HA) infections (Oliveira et al, 2002). Glycopeptides such as vancomycin are the primary treatment option for severe infections caused by Gram-positive bacteria, including MRSA and most strains of multidrug-resistant S. aureus (Walsh, 1999). The first completely resistant clinical isolate of S. aureus (MIC > 1,024 μg/ml) was reported in July 2002 in the United States (Centers for Disease Control and Prevention, 2002a)
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