CINXE.COM

<!DOCTYPE html><html lang="en-US"><head><title>Just a moment...</title><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta http-equiv="X-UA-Compatible" content="IE=Edge"><meta name="robots" content="noindex,nofollow"><meta name="viewport" content="width=device-width,initial-scale=1"><style>*{box-sizing:border-box;margin:0;padding:0}html{line-height:1.15;-webkit-text-size-adjust:100%;color:#313131;font-family:system-ui,-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Helvetica Neue,Arial,Noto Sans,sans-serif,Apple Color Emoji,Segoe UI Emoji,Segoe UI Symbol,Noto Color Emoji}body{display:flex;flex-direction:column;height:100vh;min-height:100vh}.main-content{margin:8rem auto;max-width:60rem;padding-left:1.5rem}@media (width <= 720px){.main-content{margin-top:4rem}}.h2{font-size:1.5rem;font-weight:500;line-height:2.25rem}@media (width <= 720px){.h2{font-size:1.25rem;line-height:1.5rem}}#challenge-error-text{background-image:url(data:image/svg+xml;base64,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);background-repeat:no-repeat;background-size:contain;padding-left:34px}@media (prefers-color-scheme:dark){body{background-color:#222;color:#d9d9d9}}</style><meta http-equiv="refresh" content="120"></head><body class="no-js"><div class="main-wrapper" role="main"><div class="main-content"><noscript><div class="h2"><span id="challenge-error-text">Enable JavaScript and cookies to continue</span></div></noscript></div></div><script>(function(){window._cf_chl_opt={cvId: '3',cZone: "www.annualreviews.org",cType: 'non-interactive',cRay: '8e9bcb30bb24a1ad',cH: 'hQNVs2fTKpMQglJFLdwdZKF39CMPv9wq00ea0l1j9p4-1732811962-1.2.1.1-11ObenHFKcl2_HJ.8gMZg38MZrDXJDs81xPuqXlH8fk94WrGs9cBCZKVxOy8zKgA',cUPMDTk: "\/doi\/10.1146\/annurev.micro.62.081307.162948?__cf_chl_tk=8DAixacfQ91Ja.MOkxqUR.00PT9upBMTz5O8ALCT2DY-1732811962-1.0.1.1-PXi25N66k7AuyBMwUGJAC_x45GYiWsgWFQ1b172zmZM",cFPWv: 'b',cITimeS: '1732811962',cTTimeMs: '1000',cMTimeMs: '120000',cTplC: 0,cTplV: 5,cTplB: 'cf',cK: "",fa: "\/doi\/10.1146\/annurev.micro.62.081307.162948?__cf_chl_f_tk=8DAixacfQ91Ja.MOkxqUR.00PT9upBMTz5O8ALCT2DY-1732811962-1.0.1.1-PXi25N66k7AuyBMwUGJAC_x45GYiWsgWFQ1b172zmZM",md: "mKSYo77y0MXtGZq7SGy.PzontUZbn6fOYWkkHv96EQY-1732811962-1.2.1.1-f.IkXo2TLzfMO.Csza42XcxU2FYUtKBlwWk28ymWx8Dwbjt6YojwH0haxfLMSBgLQ_AqZbR.mDa1NV8eN1iIkV_Uf56_519N4zKV2C8SvhsrVRhcDifKSWmnTQIZQ9rbwQ7IZzbCzXVdV_8I0bDs4p_eBdzZ7zP9hWjN2aWP4462xq8jquj20_vFtqx6AYdy7hB1BgDDwSaCOeFTbQQW6JTyLtBxodQ44K9AIx8MbPFjejabJA9VA4qIu3OHAzbCsTdn6J_lfSZZbOYU3u6hwhTeuUtNdz47s9TxfxNVtOHAjakBEFQoHKaGa09VayGrdcYslVnzw4xSaUq2TI_M6KnvKdnLgN78VTxsKTJxYzjcTVfQKXpPrUpXYQmxQeI9ZY74WMCu22GrKae6p3BaIg9VnIsiTbw35WRkvLa415v.oikFhq._2fnl1RSqCVyUm8EvB615K1kJaZEGDnHxFIJQZeM8E5zJZPYnctFKGYpHBZVM.eyb8ubqIirqQ3cIMn0j4Pe.XzIujUbrzlYgB5uUY_NeWF7LwrfbImL8H7JRiBwvIiWJ7Z_0fbFdBeSFo3yxRKdUwj7PxMe.70gbL6Y7KRbrYnZXqp0vWnOvWSwlNwSK9tLoEOJEx0BeQHtF_ObdUR7iSY7GhnXgPUnewHmZU8ON0CfG4UNYwIFesFHgtUDhr1B1pCt0bRztU_vE2bSCVTuZwREo6gjCnXC0FP6FZ8R3zbxYUvFgRf..HAUasbTX6XJGhEA2RKV9brRxkM7rzuI4AFi1_La8rhi3woiOj6x9gNk29QvCvUunxm4Q0fJHH5Bd3719sUpP4HlgN77ge.lOj1wDxoZOtJGsF2x_7SKiHuh9Ram30AhJ4vUk3f0reT8eVjbKfqAVy7bQHKopOWj1..TAzEi52.c2DnTQ9P2kQxmRhpaXWvo0UZjHjXFpJqO7EuOklmsxlWLExAmQQ8OpU4u.mgT6SpAFb_iRIBMwheRn8nMv.X9CPgKkNGLCluYNTOzAM2dJFFxbihQoGqcHdlEuGWoINo4EwTxvrkTw8z..vaGCrvTbLJ0_SgzT4XF.RcfIhny3L4nwPCr4Ct_HnXQxdYmUC3K.GgPAuT5EfnsREtTDB_jflfhHb3YhXuiRlGy6_dF0xS.Rr8VRKT0NvglCjXsfLBt5SuFCnjbmA3igAX5GAQEGSYIzinxfuXR2YZbxNhO.qWKAZmFn92IifFWa20YhwrxGKjZI0tudanTF70T0An3e6TPz7WJ9yVEsgB3tiPGq.8XIcIZCV7byDS_LM8LPQzTGWW97zULHD6S5CXlGwzRfyH2S.d5..n5yHJ_9imWNa1.w6h5XZAZT6XQ8yt6PB6v4zBP.s7EzEPIePip8bJ3bEAQDT28qg5Eu53sqney.6lr0iobuKP4JFHJlvVBo6CqBhaVNor9fUemjaXg5QQ6o1cyn.yf0PB__Zr2eIcHrmX0sriQd4U7WewDWx5VWJ7AtSoR4GUV65s4mbyA.Qhkgwyx9RO4Ls8pSOr7keKrQXRhwAnIvXTF_r29ywqak_aLYORGG7K.sUr_.AmTXOlmsJte1Mz7pMmV_kQTN5cB1_8StffVgXRGfYHnK8COCuIzF8f8gDlWv09giNETN7Mmpb5kbKDmbUKxZWjMyy5yxebe7QBQRTbtsgK_O6njwkGPKQNeLgmSYyIBCMXvcYRflgXxdf43BGZxCcoCTuTyoIvx9bdJE5WcStUVUGWJP8Lp_LFM4rpPN1qFxZogidReNhAWoK0HRNd0GA.1a379oeTjUfUveWC12OXcOzZhZMTe.Y5bFQKDuLp84I56TE65lWhZ3OWxlhVVpIL8iXkmrOh0TCobRFrhyzpbjE3xoorbCF3j2uCsQHpF2GgMmQN6Z63dutvdXIK32t_aUouHjCdnknYGRn2NQfn3rJbkeIZ08wU03L5spxKDQurpDJVlkmoRug7uBR65.HbyfFYpHbRtkerYJF4TxUR5uH9RyPvqlhIQTT39MKnEeNeCIwjsY1UYE9vuyCkHuS8LhJWqHI1ek",mdrd: "ToH8xoCEOtU3sSLb6gXrW1n3Sw6CqPTkYFV6gkS9Egc-1732811962-1.2.1.1-I_MgtyJSK7BhegtJSadGxtFloHhQZf.lnLwJFJ3MHe7wjGZPSlxABYZ5CSN7LgJj0fCccPPdU3fvpv1maCZnBAGvUEhW9Ub48GFKW_sMP.YlTveMlEThb.b62N.f8tG.7xUCRgLye5ZRERSHVomlI7lNBTPP7cY9.1L2nV1Ror3JnPR5ivSCj70KKv69jFRdAVOWdQnz10VBmx9b5KaLsQ0waNgDHItUcWP.5XGepaD613c_wCU1qk4gzV0KAzBB57fGEYylxqLHl0NybuDqB12azqVp9IF6hRhvB9D9LZ0TQ_Wbtz10pSC36dyohnk_OZY8POOJSPp5ewuWhzaVuraS7Ik3Slr6nj0w2Z8YHoZgH31cX4_8a3QtavicphoQxG8tFWzhE8c65aAqHez3t1UQmYvQ7e0C8.9atp2uwMS_KH7zPv53CEfDra80DaNqHhyANUbKwQhS1hPAY7iiRb2kCatOngFVJfdwgttYvSppQkYsZdhTeJDcUvY7z9E_I1GoQldgNOFBMq_dHcFB8iB9cbrnPP2EkfyQFJDzK61SWa15W3SwovvmLbPXIwWBrHeXfCeGWMsVwaJacQUWK5ajN_T2QFrWx.OZ1kUnCSffObVIksMsnyBqi2anyexA.Q_nL.Yx6SMusaQcw.EFW6c0pzRMKJ4GLvdDcDwoKeuMiQ9LKVZ91L7U_157xbSpkKSnmftf26gfZYLxCBK9Hba70O4siaEEiO5C.mfNMvsXNDJzj8F3f5SC0qeY40bdc1m_RfmDV4sut6oEuGnuzKrtf9I5OPWI4gqyUOizYC6.A2US_ndQsz2HHYDIGLETp9BKlkVWYTiSVhTReRdcM4Tc_f.t0biwi6B9HfuN35oC7xCckRPaiXQByw1DBkavI4JwDMGHC_XFfokc4ArKw9sy4Y7Lf6BslYIvI9moiZdWr3wgQogQMos7L9vstmPmYaGMpmYnYrJY9gAq5Jo276pb3TNWfZZitzZNE9R3LBLMb18QQuqaGlXUkId1W1_jww.LiI34LNC3Cu4cLTGzgy1v8Aw14qFFDvPeFfQ5UNpRrPkY87c8K3AvEBBDKGNfjSZE4qb_TNWre3P7CC1BjlI0Fb1JqA3CYrolsFbb32kKTzYgWwxP.7UqHVqsC8MxxWY6Bv0HOzia2S_PUjZjthjRPYTiRwIrRlCtrolDTVPkyyxnW1lPu.9jfDazeSfM1gvjDVpVzOkYvPxyOil0m7rrePS9YqcvUvnr_JH3NBgUJvIJzLo3D1RCkTXBhry1jqR2LDleVSha_LGpg7xwiRtrQOqBsEuPDVWnxHy4.6Mf_5wXL4Yktm1LO5PpWrofVyDeXSB3Uw3w.Dgj3x3pyF87Wfe1T.6YbnBSMxMZsG8vyApghyFOhh5GahuuDLYSwFwzJCHipaTBAXvi3FMNilXdMwdoLCaDG59VaSxOgkgUdwyvKtaRiGLZzAr5RzHVmke1BKE.vdB_ymRhtrGeXTmzJuspsxCHeErzanamBvdIxd.kOA5BvKGkc.0aFZ1ZJ4v_oDVr3vb7zM7p.I4PHw8x3k5SumLpBpLfbaGw6Kws3H9gQkYdvx.B3OShHmzJ38diaE7Ynbm7KoY1cxZKqA8Sp40jlZld0cBsXGgA4aTt70psnrCdzBds.KG5MPErvCjjem6VByWyZCbKedookqB5vZDkFaQVVZDd8NoZpOQLmEhMDOg8ZWOxW51hKxR78SI..ycM9HKulvdnB8O94bgqztJ77k0ia6Tu7AzBuChlVZIQwcU5NR75nEZsmILch_8tJaDPaMgswxwuwq.ygBtOWPhwOh_PdFWFFaljPScVlc7r9T6h93GEduq0PabRFGEGV3BZRrr7s5a6pw2WsXCxweN82VxMMYtJU91BHrUzkI_PwwQijMfDAdZH37fmr0P2dNhwV.4okuxz.wY4QwHyNC9sAV3htj1mE5YKTh.OnJ5P_5.zN8TeHPXW26Iu"};var cpo = document.createElement('script');cpo.src = '/cdn-cgi/challenge-platform/h/b/orchestrate/chl_page/v1?ray=8e9bcb30bb24a1ad';window._cf_chl_opt.cOgUHash = location.hash === '' && location.href.indexOf('#') !== -1 ? '#' : location.hash;window._cf_chl_opt.cOgUQuery = location.search === '' && location.href.slice(0, location.href.length - window._cf_chl_opt.cOgUHash.length).indexOf('?') !== -1 ? '?' : location.search;if (window.history && window.history.replaceState) {var ogU = location.pathname + window._cf_chl_opt.cOgUQuery + window._cf_chl_opt.cOgUHash;history.replaceState(null, null, "\/doi\/10.1146\/annurev.micro.62.081307.162948?__cf_chl_rt_tk=8DAixacfQ91Ja.MOkxqUR.00PT9upBMTz5O8ALCT2DY-1732811962-1.0.1.1-PXi25N66k7AuyBMwUGJAC_x45GYiWsgWFQ1b172zmZM" + window._cf_chl_opt.cOgUHash);cpo.onload = function() {history.replaceState(null, null, ogU);}}document.getElementsByTagName('head')[0].appendChild(cpo);}());</script></body></html>