美国科学家发现，链球菌基因中一个简单的基因突变，能降低人类患坏死性筋膜炎(necrotizing fasciitis)的可能性。而且他们还证实，使该基因上发生突变的片段失活，也可降低人类患此病的几率。该研究报告发表在近期的PNAS杂志网络版上。
坏死性筋膜炎是一种罕见且严重的疾病，患此病的死亡率约为30%。A组链球菌(group A Streptococcus,GAS)感染是导致该疾病发生的主要原因。
Musser等人从患链球菌相关疾病的患者（包括坏死性筋膜炎患者）中分离出12种GAS菌系，并对其基因组序列进行分析。分析表明，链球菌基因组自身发生的突变可降低人类患坏死性筋膜炎的可能性。在该研究中，Musser等人对比了从患者中收集的255个GAS的基因组，研究人员发现单个核苷酸插入到链球菌金属转运体调节子(metal transporter of streptococcus regulator,MtsR)基因产生突变，MtsR基因突变导致MtsR蛋白的表达提前终止。
研究还表明，由于突变导致该基因一个片段“关闭”，可减少该疾病对软组织的破坏程度。
推荐原始出处：
PNAS January 4, 2010, doi: 10.1073/pnas.0911811107
Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis
Randall J. Olsena, Izabela Sitkiewicza, Ara A. Ayerasa, Vedia E. Gonulala, Concepcion Cantua, Stephen B. Beresa, Nicole M. Greena, Benfang Leib, Tammy Humbirdc, Jamieson Greaverc, Ellen Changa, Willie P. Ragasaa, Charles A. Montgomeryd, Joiner Cartwright Jr.e, Allison McGeerf, Donald E. Lowg, Adeline R. Whitneyh, Philip T. Caglea, Terry L. Blasdelc, Frank R. DeLeoh and James M. Mussera,1
aCenter for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030
bDepartment of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717
cAnimal Care Operations, University of Houston, Houston, TX 77204
dComPath, Jay, OK 74346
eDepartment of Pathology, Baylor College of Medicine, Houston, TX 77030
fDepartment of Microbiology, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada;
gOntario Agency for Health Protection and Promotion, and University of Toronto, Toronto, ON M5S 1A1
hLaboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840
Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis (“flesh-eating disease”). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the ΔmtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.
