Disruption of homocitrate synthase genes in Candida albicans affects growth but not virulence.
Two genes, LYS21 and LYS22, encoding isoforms of homocitrate synthase, an enzyme catalysing the first committed step in the lysine biosynthetic pathway, were disrupted in Candida albicans using the SAT1 flipper strategy. The double null lys21Δ/lys22Δ mutant lacked homocitrate synthase activity and exhibited lysine auxotrophy in minimal media that could be fully rescued by the addition of 0.5-0.6 mM L: -lysine. On the other hand, its virulence in vivo in the model of disseminated murine candidiasis appeared identical to that of the mother, wild-type strain. These findings strongly question a possibility of exploitation of homocitrate synthase and possibly also other enzymes of the lysine biosynthetic pathway as targets in chemotherapy of disseminated fungal infections.
Kur
Krzysztof
K
Department of Pharmaceutical Technology & Biochemistry, Gdańsk University of Technology, 11/12 Narutowicza St., 80-233, Gdańsk, Poland.
Gabriel
Iwona
I
Morschhäuser
Joachim
J
Barchiesi
Francesco
F
Spreghini
Elisabetta
E
Milewski
Sławomir
S
D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000254:growth & development* / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology / Q000401:mortality; D003470:Culture Media / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques; D005800:Genes, Fungal; D008239:Lysine / Q000378:metabolism; D051379:Mice; D007652:Oxo-Acid-Lyases / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism*
D003470:Culture Media; D037521:Virulence Factors; C021365:homocitrate synthase; D007652:Oxo-Acid-Lyases; D008239:Lysine