A Novel Antimicrobial Coating Represses Biofilm and Virulence-Related Genes in Methicillin-Resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has become an important cause of hospital-acquired infections worldwide. It is one of the most threatening pathogens due to its multi-drug resistance and strong biofilm-forming capacity. Thus, there is an urgent need for novel alternative strategies to combat bacterial infections. Recently, we demonstrated that a novel antimicrobial surface coating, AGXX®, consisting of micro-galvanic elements of the two noble metals, silver and ruthenium, surface-conditioned with ascorbic acid, efficiently inhibits MRSA growth. In this study, we demonstrated that the antimicrobial coating caused a significant reduction in biofilm formation (46%) of the clinical MRSA isolate, S. aureus 04-02981. To understand the molecular mechanism of the antimicrobial coating, we exposed S. aureus 04-02981 for different time-periods to the coating and investigated its molecular response via next-generation RNA-sequencing. A conventional antimicrobial silver coating served as a control. RNA-sequencing demonstrated down-regulation of many biofilm-associated genes and of genes related to virulence of S. aureus. The antimicrobial substance also down-regulated the two-component quorum-sensing system agr suggesting that it might interfere with quorum-sensing while diminishing biofilm formation in S. aureus 04-02981.

Novel Antimicrobial Cellulose Fleece Inhibits Growth of Human-Derived Biofilm-Forming Staphylococci During the SIRIUS19 Simulated Space Mission

“…Extensive bacterial growth occurred on uncoated control samples ( Figure 2C). This supports evidence from earlier studies (Guridi et al, 2015;Landau et al, 2017;Loi et al, 2018;Vaishampayan et al, 2018;Sobisch et al, 2019) and demonstrates that the antimicrobial, growth-inhibiting properties of AGXX R remain effective when applied to the new carrier materials.…”

“…Biofilm formation test was carried out according to Vaishampayan et al (2018). Briefly, bacterial isolates grown overnight in LB medium at 37 • C with shaking (150 rpm) were diluted to an initial OD 600 of 0.05 and re-grown to exponential phase (OD 600 ∼1.5).…”

“…Studies using next generation RNA sequencing revealed that exposure to AGXX R induces a broad general stress response in E. faecalis with up-regulation of heat shock genes and a strong oxidative stress response (Clauss-Lendzian et al, 2018). Similar studies of MRSA strains exposed to AGXX R revealed a thiol-specific oxidative stress response (Loi et al, 2018) and repression of genes for biofilm formation, virulence factors, and quorum sensing systems (Vaishampayan et al, 2018). To date, bacterial resistance against AGXX R has not been observed, making AGXX R a promising broadspectrum antimicrobial.…”

Molecular epidemiology and virulence factors of methicillin‐resistant Staphylococcus aureus isolated from patients with bacteremia

“…Methicillin‐resistant Staphylococcus aureus causes various diseases such as skin and soft tissue infections, endocarditis, and bone and joint infections . Among these infections, MRSA bacteremia (MRSAB) is one of the most common problems because of the associated high mortality rate.…”

“…Methicillin-resistant Staphylococcus aureus causes various diseases such as skin and soft tissue infections, endocarditis, and bone and joint infections. 5,6 Among these infections, MRSA bacteremia (MRSAB) is one of the most common problems because of the associated high mortality rate. The mortality rate for patients with MRSAB is about 30%-40%, [7][8][9] which is about twice that reported for methicillin susceptible S aureus bacteremia (MSSAB).…”