Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates. Citral has been studied in the pharmaceutical industry and has shown antimicrobial activity. This study aimed to analyze the antimicrobial activity of citral in inhibiting biofilm formation and modulating virulence genes, with the ultimate goal of finding a strategy for treating infections caused by MRSA strains. Citral showed antimicrobial activity against MRSA isolates with minimum inhibitory concentration (MIC) values between 5 mg/mL (0.5%) and 40 mg/mL (4%), and minimum bactericidal concentration (MBC) values between 10 mg/mL (1%) and 40 mg/mL (4%). The sub-inhibitory dose was 2.5 mg/mL (0.25%). Citral, in an antibiogram, modulated synergistically, antagonistically, or indifferent to the different antibiotics tested. Prior to evaluating the antibiofilm effects of citral, we classified the bacteria according to their biofilm production capacity. Citral showed greater efficacy in the initial stage, and there was a significant reduction in biofilm formation compared to the mature biofilm. qPCR was used to assess the modulation of virulence factor genes, and icaA underexpression was observed in isolates 20 and 48. For icaD, seg, and sei, an increase was observed in the expression of ATCC 33,591. No significant differences were found for eta and etb. Citral could be used as a supplement to conventional antibiotics for MRSA infections.

Highlights

  • Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates

  • After defining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the subinhibitory concentration of citral was determined to verify the modulation of virulence factors without affecting the viability of microorganisms

  • Our results showed that 5 mg/mL (0.5%) citral was able to modulate the antimicrobial activity of different antibiotics through synergistic, antagonistic, or indifferent actions

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Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates. The S. aureus strain resistant to almost all β-lactam antibiotics, determined by a chromosomal gene mecA that encodes altered PBPs (PPB2a or PBP2’), is referred to as methicillin-resistant Staphylococcus aureus (MRSA) and can be found in hospital settings (HA-MRSA), as well as in the community (CA-MRSA)[5]. Infections caused by these bacteria are linked to higher mortality rates and higher treatment costs for an overburdened health system compared to infections caused by strains of S. aureus sensitive to methicillin (MSSA)[6,7,8]. These genes provide bacteria with the ability to infect and c­ olonize[9,10], resulting in food poisoning and other types of infections in humans and animals

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