Functional modularity of the arginine catabolic mobile element contributes to the success of USA300 methicillin-resistant Staphylococcus aureus.
Functional modularity of the arginine catabolic mobile element contributes to the success of USA300 methicillin-resistant Staphylococcus aureus.
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DOI：
10.1016/j.chom.2012.11.012
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发表时间：
2013-01-16
影响因子：
30.3
通讯作者：
Richardson AR
中科院分区：
文献类型：
--
作者：
Thurlow LR;Joshi GS;Clark JR;Spontak JS;Neely CJ;Maile R;Richardson AR
成功的USA 300社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）谱系主要引起皮肤和软组织感染（SSTI），并且与精氨酸分解代谢移动的元件（ACME）的携带高度相关。然而，在SSTI期间ACME对USA 300适应性的贡献仍然不完全清楚。我们表明，组成ACME编码的精氨酸脱亚胺酶系统（弧）允许USA 300在模拟人类皮肤的酸性环境中茁壮成长。因此，ACME-Arc驱动宿主多胺的过量产生，所述宿主多胺是对S唯一有毒的化合物。金黄色。为了减轻这种情况，ACME还编码SpeG，这是一种多胺抗性酶，对于在鼠SSTI模型中对抗过量的宿主多胺至关重要。抑制宿主多胺的产生不仅恢复了感染伤口内ΔspeG的持久性，而且严重改变了宿主的愈合过程，这意味着多胺在协调伤口愈合反应中起着不可或缺的作用。总之，这些数据强调了ACME的功能模块性及其对USA 300 CA-MRSA成功的贡献。
The successful USA300 Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) lineage predominantly causes skin and soft tissue infections (SSTIs) and is highly associated with carriage of the Arginine Catabolic Mobile Element (ACME). However, the contribution of ACME to USA300 fitness during SSTIs remains incompletely understood. We show that the constitutive ACME-encoded arginine-deiminase system (Arc) allows USA300 to thrive in acidic environments that mimic human skin. Consequently, ACME-Arc drives excessive production of host polyamines, compounds uniquely toxic to S. aureus. To mitigate this, ACME also encodes SpeG, a polyamine-resistance enzyme that is essential for combating excess host polyamines in a murine SSTI model. Inhibiting host polyamine production not only restored ΔspeG persistence within infected wounds but also severely altered the host healing process, implying that polyamines play integral roles in coordinating the wound-healing response. Together, these data underscore the functional modularity of ACME and its contribution to the success of USA300 CA-MRSA.
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影响因子：
168.9
作者：
DeLeo, Frank R.;Otto, Michael;Kreiswirth, Barry N.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.
影响因子：
5.7
作者：
Fuller JR;Vitko NP;Perkowski EF;Scott E;Khatri D;Spontak JS;Thurlow LR;Richardson AR
通讯作者：
Richardson AR
影响因子：
10.3
作者：
ELBAZE, P;MILANO, G;ORTONNE, JP
通讯作者：
ORTONNE, JP
影响因子：
5.2
作者：
Ellington, Matthew J.;Yearwood, Lianne;Kearns, Angela M.
通讯作者：
Kearns, Angela M.
DOI：
10.1097/ta.0b013e31820d18a6
发表时间：
2011-03-01
影响因子：
--
作者：
Neely, Crystal J.;Maile, Robert;Cairns, Bruce A.
通讯作者：
Cairns, Bruce A.