The promising anti-virulence activity of candesartan, domperidone, and miconazole on Staphylococcusaureus
Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S . aureus strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of S. aureus may generate weaker selection...
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Veröffentlicht in: | Brazilian journal of microbiology 2022, Vol.53 (1), p.1-18 |
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Sprache: | eng |
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Zusammenfassung: | Staphylococcus
aureus
is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant
S
.
aureus
strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of
S.
aureus
may generate weaker selection for resistant strains, anti-virulence agents disarm the pathogen instead of killing it. In this study, the ability of the FDA-approved drugs domperidone, candesartan, and miconazole as inhibitors of
S.
aureus
virulence was investigated. The effect of tested drugs was evaluated against biofilm formation, lipase, protease, hemolysin, and staphyloxanthin production by using phenotypic and genotypic methods. At sub-inhibitory concentrations, candesartan, domperidone, and miconazole showed a significant inhibition of hemolysin (75.8–96%), staphyloxanthin (81.2–85%), lipase (50–65%), protease (40–64%), and biofilm formation (71.4–90%). Domperidone and candesartan have similar activity and were more powerful than miconazole against
S.
aureus
virulence. The hemolysins and lipase inhibition were the greatest under the domperidone effect. Candesartan showed a remarkable reduction in staphyloxanthin production. The highest inhibitory effect of proteolytic activity was obtained with domperidone and candesartan. Biofilm was significantly reduced by miconazole. Expression levels of
crtM
,
sigB
,
sarA
,
agrA
,
hla
,
fnbA
, and
icaA
genes were significantly reduced under candesartan (68.98–82.7%), domperidone (62.6–77.2%), and miconazole (32.96–52.6%) at sub-MIC concentrations. Candesartan showed the highest inhibition activity against
crtM
,
sigB
,
sarA
,
agrA
,
hla
, and
icaA
expression followed by domperidone then miconazole. Domperidone showed the highest downregulation activity against
fnbA
gene. In conclusion, candesartan, domperidone, and miconazole could serve as anti-virulence agents for attenuation of
S.
aureus
pathogenicity. |
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ISSN: | 1517-8382 1678-4405 |
DOI: | 10.1007/s42770-021-00655-4 |