Subbian Selvakumar, Mehta Parmod K, Cirillo Suat L G, Cirillo Jeffrey D
Dept, Microbial and Molecular Pathogenesis, Texas A&M University Health Sciences Center-College of Medicine, College Station, TX 77843-1114, USA.
BMC Microbiol. 2007 Jan 19;7:4. doi: 10.1186/1471-2180-7-4.
Mycobacteria have developed a number of pathways that provide partial protection against both reactive oxygen species (ROS) and reactive nitrogen species (RNS). We recently identified a locus in Mycobacterium marinum, mel2, that plays a role during infection of macrophages. The molecular mechanism of mel2 action is not well understood.
To better understand the role of the M. marinum mel2 locus, we examined these genes for conserved motifs in silico. Striking similarities were observed between the mel2 locus and loci that encode bioluminescence in other bacterial species. Since bioluminescence systems can play a role in resistance to oxidative stress, we postulated that the mel2 locus might be important for mycobacterial resistance to ROS and RNS. We found that an M. marinum mutant in the first gene in this putative operon, melF, confers increased susceptibility to both ROS and RNS. This mutant is more susceptible to ROS and RNS together than either reactive species alone.
These observations support a role for the M. marinum mel2 locus in resistance to oxidative stress and provide additional evidence that bioluminescence systems may have evolved from oxidative defense mechanisms.
分枝杆菌已形成多种途径,可对活性氧(ROS)和活性氮(RNS)提供部分保护。我们最近在海分枝杆菌中鉴定出一个基因座mel2,它在巨噬细胞感染过程中发挥作用。mel2作用的分子机制尚不清楚。
为了更好地理解海分枝杆菌mel2基因座的作用,我们通过计算机分析这些基因的保守基序。在mel2基因座与其他细菌物种中编码生物发光的基因座之间观察到显著相似性。由于生物发光系统可在抵抗氧化应激中发挥作用,我们推测mel2基因座可能对分枝杆菌抵抗ROS和RNS很重要。我们发现该假定操纵子中第一个基因melF的海分枝杆菌突变体对ROS和RNS的敏感性增加。该突变体对ROS和RNS共同作用的敏感性高于单独任何一种活性物质。
这些观察结果支持海分枝杆菌mel2基因座在抵抗氧化应激中的作用,并提供了额外证据表明生物发光系统可能从氧化防御机制进化而来。