Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA.
Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.02299-17. Print 2018 Apr.
, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous genes that are evolutionarily conserved. One of these, the essential gene , encodes the catalytic subunit of glucan synthase, which is the target of echinocandin drugs and also serves as a site of drug resistance. The other two glucan synthase-encoding genes, and , are also expressed, but their roles in resistance are considered unimportant. However, we report here that expression of is upregulated in strains lacking either or Furthermore, in contrast to what is observed in heterozygous deletion strains, cells lacking or contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs, and consistently are tolerant to cell wall-damaging agents. Our data indicate that and can act as negative regulators of , thereby influencing echinocandin susceptibility.
白念珠菌是一种流行的人类机会性真菌病原体，具有包含三个同源基因的二倍体基因组，这些基因在进化上是保守的。其中之一，必需基因 ，编码葡聚糖合酶的催化亚基，该酶是棘白菌素类药物的靶标，也是耐药性的部位。另外两个葡聚糖合酶编码基因 和 也被表达，但它们在耐药性中的作用被认为不重要。然而，我们在这里报告，在缺乏 或 的菌株中， 的表达上调。此外，与在杂合 缺失菌株中观察到的情况相反，缺乏 或 的细胞含有更多的细胞壁葡聚糖，对棘白菌素类药物的耐药性增加，并且一致耐受细胞壁破坏剂。我们的数据表明， 和 可以作为 的负调节剂，从而影响棘白菌素类药物的敏感性。
