Engleberg N C, Heath A, Miller A, Rivera C, DiRita V J
Departments of Internal Medicine and Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
J Infect Dis. 2001 Apr 1;183(7):1043-54. doi: 10.1086/319291. Epub 2001 Mar 1.
CsrS/CsrR is a 2-component system in Streptococcus pyogenes that negatively regulates hyaluronic capsule and several exotoxins. To detect spontaneous mutations in csrRS, mucoid and large colony variants of M1 strain MGAS166 were isolated from experimental murine skin infections. By use of complementation with a csrRS(+) plasmid, relevant mutations were also detected in 7 of 12 human clinical isolates. The presence of spontaneous mutants in mouse infection was associated with larger, more necrotic lesions. Most spontaneous changes in CsrR resulted from single amino acid substitutions, whereas most csrS mutations were frameshift or nonsense mutations. In 2 instances, IS1548 insertions were found in csrS. Experimental inoculation of mixtures of wild-type (wt) and csrRS(-) bacteria yielded larger, more necrotic lesions than did either strain at twice the inoculum, which suggests that these variants may exhibit pathogenic synergy. Spontaneous emergence of csrRS(-) mutants in vivo enhances the virulence of wt bacteria and increases severity of murine skin infection.
CsrS/CsrR是化脓性链球菌中的一种双组分系统，对透明质酸荚膜和几种外毒素起负调控作用。为了检测csrRS中的自发突变，从实验性小鼠皮肤感染中分离出M1菌株MGAS166的黏液样和大菌落变体。通过用csrRS(+)质粒进行互补，在12株人类临床分离株中的7株中也检测到了相关突变。小鼠感染中自发突变体的存在与更大、更具坏死性的病变相关。CsrR中的大多数自发变化是由单个氨基酸取代引起的，而大多数csrS突变是移码突变或无义突变。在2个实例中，在csrS中发现了IS1548插入。野生型（wt）和csrRS(-)细菌混合物的实验性接种产生的病变比接种量两倍的任一菌株都更大、更具坏死性，这表明这些变体可能表现出致病协同作用。体内csrRS(-)突变体的自发出现增强了wt细菌的毒力，并增加了小鼠皮肤感染的严重程度。
