Bactericidal activity of octenidine against Staphylococcus aureus harbouring genes encoding multidrug resistance efflux pumps

ABSTRACT MgrA is a global regulator in Staphylococcus aureus that controls the expression of diverse genes encoding virulence factors and multidrug resistance (MDR) efflux transporters. We identified pknB, which encodes the (Ser/Thr) kinase PknB, in the S. aureus genome. PknB was able to autophosphorylate as well as phosphorylate purified MgrA. We demonstrated that rsbU, which encodes a Ser/Thr phosphatase and is involved in the activation of the SigB regulon, was able to dephosphorylate MgrA-P but not PknB-P. Serines 110 and 113 of MgrA were found to be phosphorylated, and Ala substitutions at these positions resulted in reductions in the level of phosphorylation of MgrA. DNA gel shift binding assays using norA and norB promoters showed that MgrA-P was able to bind the norB promoter but not the norA promoter, a pattern which was the reverse of that for unphosphorylated MgrA. The double mutant MgrAS110A-S113A bound to the norA promoter but not the norB promoter. The double mutant led to a 2-fold decrease in norA transcripts and a 2-fold decrease in the MICs of norfloxacin and ciprofloxacin in strain RN6390. Thus, phosphorylation of MgrA results in loss of binding to the norA promoter, but with a gain of the ability to bind the norB promoter. Loss of the ability to phosphorylate MgrA by Ala substitution resulted in increased repression of norA expression and in reductions in susceptibilities to NorA substrates.

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Lippia graveolens HBK oleoresins, extracted by supercritical fluids, showed bactericidal activity against multidrug resistance Enterococcus faecalis and Staphylococcus aureus strains

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2021.2008417 ◽

2021 ◽

pp. 1-33

Author(s):

Oscar de Jesús Calva-Cruz ◽

Nallely S. Badillo-Larios ◽

Antonio De León-Rodríguez ◽

Eduardo Espitia-Rangel ◽

Raúl González-García ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Multidrug Resistance ◽

Enterococcus Faecalis ◽

Supercritical Fluids ◽

Bactericidal Activity ◽

And Staphylococcus Aureus

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Staphylococcus aureus Efflux Pumps and Tolerance to Ciprofloxacin and Chlorhexidine following Induction by Mupirocin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01845-21 ◽

2021 ◽

Author(s):

Q.C. Truong-Bolduc ◽

Y. Wang ◽

J. L. Reedy ◽

J.M. Vyas ◽

D.C. Hooper

Keyword(s):

Staphylococcus Aureus ◽

Efflux Pumps ◽

Induced Expression ◽

Expression Of Genes ◽

Genes Encoding

Mupirocin induced expression of genes encoding efflux pumps NorA and MepA as well as a YFP fluorescence reporter of NorA. Mupirocin exposure also produced reduced susceptibility to pump substrates ciprofloxacin and chlorhexidine, a change that was dependent on intact norA and mepA , respectively.

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GC-MS Profile and Enhancement of Antibiotic Activity by the Essential Oil of Ocotea odorífera and Safrole: Inhibition of Staphylococcus aureus Efflux Pumps

Antibiotics ◽

10.3390/antibiotics9050247 ◽

2020 ◽

Vol 9 (5) ◽

pp. 247 ◽

Cited By ~ 1

Author(s):

Ray S. Almeida ◽

Priscilla R. Freitas ◽

Ana Carolina J. Araújo ◽

Irwin R. A. Menezes ◽

Eduardo L. Santos ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Essential Oil ◽

Ethidium Bromide ◽

Efflux Pump ◽

Efflux Pumps ◽

Phytochemical Analysis ◽

Broth Microdilution Method ◽

Genes Encoding ◽

Resistant Strains ◽

Efflux Proteins

Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odorífera (EOOO) and safrole against efflux pump (EP)-carrying strains. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial and antibiotic-modulating activities of the EOOO and safrole against resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were analyzed through the broth microdilution method. The EP-inhibiting potential of safrole in association with ethidium bromide or antibiotics was evaluated using the S. aureus 1199B and K2068 strains, which carry genes encoding efflux proteins associated with antibiotic resistance to norfloxacin and ciprofloxacin, respectively. A reduction in the MIC of ethidium bromide or antibiotics was used as a parameter of EP inhibition. The phytochemical analysis identified 16 different compounds in the EOOO including safrole as the principal constituent. While the EOOO and safrole exerted clinically relevant antibacterial effects against S. aureus only, they potentiated the antibacterial activity of norfloxacin against all strains evaluated by our study. The ethidium bromide and antibiotic assays using the strains of S. aureus SA1119B and K2068, as well as molecular docking analysis, indicated that safrole inhibits the NorA and MepA efflux pumps in S. aureus. In conclusion, Ocotea odorifera and safrole presented promising antibacterial and antibiotic-enhancing properties, which should be explored in the development of drugs to combat antibacterial resistance, especially in strains bearing genes encoding efflux proteins.

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Distribution of Antiseptic Resistance GenesqacA, qacB, andsmrin Methicillin-Resistant Staphylococcus aureus Isolated in Toronto, Canada, from 2005 to 2009

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01707-10 ◽

2011 ◽

Vol 55 (6) ◽

pp. 2999-3001 ◽

Cited By ~ 58

Author(s):

Jean Longtin ◽

Christine Seah ◽

Krystal Siebert ◽

Allison McGeer ◽

Andrew Simor ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Intensive Care ◽

Intensive Care Units ◽

Methicillin Resistant Staphylococcus Aureus ◽

Efflux Pumps ◽

Chlorhexidine Gluconate ◽

Methicillin Resistant ◽

Content Type ◽

Genes Encoding

ABSTRACTDecreased susceptibility to chlorhexidine gluconate (CHDN) in methicillin-resistantStaphylococcus aureus(MRSA) is associated with theqacA,qacB, andsmrgenes, encoding efflux pumps. A total of 334 MRSA isolates were collected from two Canadian intensive care units between 2005 and 2009. We identified theqacABgenes in 7 strains (2%; 2qacAgenes and 5qacBgenes) and thesmrgene in 23 (7%) strains. CHDN minimal bactericidal concentrations were slightly higher for strains harboringsmrgenes.

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Sensitizing multi drug resistant Staphylococcus aureus isolated from surgical site infections to antimicrobials by efflux pump inhibitors

African Health Sciences ◽

10.4314/ahs.v20i4.16 ◽

2020 ◽

Vol 20 (4) ◽

pp. 1632-45

Author(s):

Baiomy Amr A ◽

Shaker Ghada H ◽

Abbas Hisham A

Keyword(s):

Staphylococcus Aureus ◽

Multidrug Resistance ◽

Ethidium Bromide ◽

Efflux Pump ◽

Surgical Site Infections ◽

Efflux Pumps ◽

Multidrug Resistant ◽

Minor Role ◽

Efflux Pump Inhibitors ◽

A Minor

Background: Staphylococcus aureus is a common hospital acquired infections pathogen. Multidrug-resistant Methicillin-resist- ant Staphylococcus aureus represents a major problem in Egyptian hospitals. The over-expression of efflux pumps is a main cause of multidrug resistance. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. This study aimed to investigate the role of efflux pumps in multidrug resistance. Methods: Twenty multidrug resistant S. aureus isolates were selected. Efflux pumps were screened by ethidium bromide agar cartwheel method and polymerase chain reaction. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilu- tion method. Results: Seventy percent of isolates showed strong efflux activity, while 30% showed intermediate activity. The efflux genes mdeA, norB, norC, norA and sepA were found to play the major role in efflux, while genes mepA, smr and qacA/B had a minor role. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. Conclusion: Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials. Keywords: Staphylococcus aureus; multidrug resistance; efflux pump inhibitors.

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