Antimicrobial agents act differently on Staphyloccocus aureus and Ralstonia eutropha flavohemoglobins.
Flavohemoglobins (FlavoHb) play a key role in bacterial resistance to nitrosative stress and NO signaling modulation. In this study, we cloned, expressed, and characterized the flavoHb from the opportunistic pathogen, Staphylococcus aureus. The higher amino-acid sequence homology is shared with that from Saccharomyces cerevisiae which was therefore used to build a model structure by homology modeling. Interestingly, the high sequence homology with S. cerevisiae did not correlate with the enzymatic and kinetic properties which are much similar to those of Escherichia coli. In vitro and aerobically, we showed that S. aureus and Ralstonia eutropha flavoHbs accept cytochrome c and oxygen as substrates. Based on this feature, we investigated the preferences for both substrates depending on miconazole or econazole addition and found that the inhibitor chemical composition is determinant.
Laboratoire de Chimie Physique, Université Paris Sud, UMR8000 CNRS, Faculté des Sciences, Bat. 350, 91405, Orsay, Cedex, France.
Aymen
A
Ezzine
Myriam
M
Moussaoui
Emna
E
El Hammi
Mohamed Nejib
MN
Marzouki
Laura
L
Baciou
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D020118:Cupriavidus necator / Q000187:drug effects* / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D006420:Hemeproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001393:Azoles; D001426:Bacterial Proteins; D006420:Hemeproteins; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; C086193:flavohemoprotein, Bacteria; D045304:Cytochromes c; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D010100:Oxygen