Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global health burden with an urgent need for antimicrobial agents. Studies have shown that host immune responses limit essential metals such as zinc during infection, leading to the limitation of bacterial virulence. Thus, the deprivation of zinc as an important co-factor for the activity of many S. aureus enzymes can be a potential antimicrobial approach. However, the effect of zinc deprivation on S. aureus and MRSA is not fully understood. Therefore, the current study aimed to dissect the effects of zinc deprivation on S. aureus hemolytic activity and biofilm formation through employing biochemical and genetic approaches to study the effect of zinc deprivation on S. aureus growth and virulence. Chemically defined media (CDM) with and without ZnCl2, was used to assess the effect of zinc deprivation on growth, biofilm formation, and hemolytic activity in methicillin-susceptible S. aureus (MSSA) RN6390 and MRSA N315 strains. Zinc deprivation decreased the growth of RN6390 and N315 S. aureus strains significantly by 1.5–2 folds, respectively compared to the zinc physiological range encountered by the bacteria in the human body (7–20 µM) (p < 0.05). Zinc deprivation significantly reduced biofilm formation by 1.5 folds compared to physiological levels (p < 0.05). Moreover, the hemolytic activity of RN6390 and N315 S. aureus strains was significantly decreased by 20 and 30 percent, respectively compared to physiological zinc levels (p < 0.05). Expression of biofilm-associated transcripts levels at late stage of biofilm formation (20 h) murein hydrolase activator A (cidA) and cidB were downregulated by 3 and 5 folds, respectively (p < 0.05) suggested an effect on extracellular DNA production. Expression of hemolysins-associated genes (hld, hlb, hla) was downregulated by 3, 5, and 10 folds, respectively, in absence of zinc (p < 0.001). Collectively the current study showed that zinc deprivation in vitro affected growth, biofilm formation, and hemolytic activity of S. aureus. Our in vitro findings suggested that zinc deprivation can be a potential supportive anti-biofilm formation and antihemolytic approach to contain MRSA topical infections.
Highlights
Staphylococcus aureus is implicated in community-acquired and nosocomial infections posing a health care burden [1,2,3]
The analysis revealed that bacterial inoculation into chemically defined medium (CDM) with no zinc (ICP = 0.007 ppm) showed an increase in zinc content after 24 h incubation to become 4 μM (ICP = 0.564 ppm)
The current pilot study focused on exploring the effect of zinc deprivation on the expression level of genes involved in hemolysins, protease, and biofilm regulation in S. aureus N315 standard strain
Summary
Staphylococcus aureus is implicated in community-acquired and nosocomial infections posing a health care burden [1,2,3]. Since the discovery of penicillin, S. aureus was one of the pathogens that developed resistance against most newly introduced antibiotics. The emergence of resistant strains and their high prevalence worldwide has resulted in the difficult eradication of staphylococcal infections in health care facilities [5,6,7]. Lipases, and nucleases enable S. aureus to obtain nutrients from host tissues to help bacterial growth [8]. Cytotoxins including the four members of the hemolysins family help S. aureus evade the host immune system [9]. The limitation of antibiotic diffusion into the biofilm community hinders the action of antibiotics [11,12,13]
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