{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:16:50Z","timestamp":1791137810228,"version":"4.1.0"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5519","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,5,11]]},"abstract":"<jats:p>To pathogenic microparasites (viruses, bacteria, protozoa, or fungi), we and other mammals (living organisms at large) are little more than soft, thin-walled flasks of culture media. Almost every time we eat, brush our teeth, scrape our skin, have sex, get bitten by insects, and inhale, we are confronted with populations of microbes that are capable of colonizing the mucosa lining our orifices and alimentary tract and proliferating in fluids and cells within us. Nevertheless, we rarely get sick, much less succumb to these infections. The massive numbers of bacteria and other micro- and not-so-micro organisms that abound and replicate in our alimentary tract and cover our skin and the mucosa lining our orifices normally maintain their communities in seemingly peaceful coexistence with the somatic cells that define us. Why don't these microbes invade and proliferate in the culture media within the soft, thin-walled flask that envelops us? Why don't they cause disease and lead to our rapid demise?<\/jats:p>","DOI":"10.1126\/science.1058879","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:52:41Z","timestamp":1027763561000},"page":"1112-1115","source":"Crossref","is-referenced-by-count":94,"title":["Why We Don't Get Sick: The Within-Host Population Dynamics of Bacterial Infections"],"prefix":"10.1126","volume":"292","author":[{"given":"Bruce R.","family":"Levin","sequence":"first","affiliation":[{"name":"Department of Biology, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rustom","family":"Antia","sequence":"additional","affiliation":[{"name":"Department of Biology, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"#cr-split#-e_1_3_1_2_2.1","unstructured":"For a population biologist-friendly review of these defenses see J. K. Spitznagel in Mechanisms of Microbial Disease X. Schaechter M. G. Medoff B. J. Eisenstein Eds. (Williams & Wilkins Baltimore MD ed. 2 1993) pp. 90-114"},{"key":"#cr-split#-e_1_3_1_2_2.2","unstructured":"H. K. Zeigler in Mechanisms of Microbial Disease M. Schaechter G. Medoff B. I. Eisenstein Eds. (Williams & Wilkins Baltimore ed. 2 1993) pp. 114-153"},{"key":"#cr-split#-e_1_3_1_2_2.3","unstructured":"W. E. Paul Ed. Fundamentals of Immunology (Lippincott Williams & Wilkins Baltimore MD ed. 4 1999)."},{"key":"e_1_3_1_3_2","first-page":"136","volume":"61","author":"Finlay B. B.","year":"1997","unstructured":"Finlay B. B., Falkow S., Microbiol. Mol. Biol. Rev. 61, 136 (1997).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058543"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","unstructured":"M. A. Nowak R. M. May Virus Dynamics: Mathematical Principles of Immunology and Virology (Oxford Univ. Press Oxford 2000).","DOI":"10.1093\/oso\/9780198504184.001.0001"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","unstructured":"A. U. Neumann et al. Science 282 103 (1998).","DOI":"10.1126\/science.282.5386.103"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1017\/S0031182000063861","volume":"110","author":"Gravenor M. B.","year":"1995","unstructured":"Gravenor M. B., McLean A. R., Kwiatkowski D., Parasitology 110, 115 (1995).","journal-title":"Parasitology"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"8359","DOI":"10.1073\/pnas.96.15.8359","volume":"96","author":"Blaser M. J.","year":"1999","unstructured":"Blaser M. J., Kirschner D., Proc. Natl. Acad. Sci. U.S.A. 96, 8359 (1999).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","unstructured":"P. G. Falk et al. Trends Microbiol. 8 321 (2000).","DOI":"10.1016\/S0966-842X(00)01780-7"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S0952-7915(99)80067-3","volume":"11","author":"Kerksiek K. M.","year":"1999","unstructured":"Kerksiek K. M., Pamer E. G., Curr. Opin. Immunol. 11, 400 (1999).","journal-title":"Curr. Opin. Immunol."},{"key":"e_1_3_1_12_2","unstructured":"\u201cI often say that when you can measure what you are speaking about and express it in numbers you know something about it: but when you cannot express it in numbers your knowledge is of a meager and unsatisfactory kind: it may be the beginning of knowledge but you have scarcely in your thoughts advanced to the stage of Science whatever the matter may be.\u201d William Thompson (Lord Kelvin) (1824\u20131907). Of course we wouldn't say that."},{"key":"e_1_3_1_13_2","unstructured":"In itself this is a considerable achievement. The integument of a mammal and the associated fluids and cilia are formidable defenses in their own right and are doubtless the primary reason that the bacteria and other microparasites that abound in the world around us on us and within us rarely cause disease. Save for trauma including the proboscis of biting arthropods it is difficult for a microbe to get through the skin of a mammal. Although not as impermeable as skin the mucosa of the alimentary tract and nasal pharyngeal passages and other orifices have formidable defenses of their own. Included among these are our microbial allies the established populations of our commensal bacteria in these habitats. Their communities and by default the mucosa in which they reside are protected from colonization by potential pathogens by a home team advantage in the competition for space and nutrients and a variety of competitive allelopathic mechanisms such as bacteriocins and microcins and predation by phage protozoa and nemotodes."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1128\/iai.59.4.1325-1333.1991","volume":"59","author":"Geme J. W. S.","year":"1991","unstructured":"Geme J. W. S., Falkow S., Infect. Immun. 59, 1325 (1991).","journal-title":"Infect. Immun."},{"key":"e_1_3_1_15_2","first-page":"2999","volume":"64","author":"DeVries F. P.","year":"1996","unstructured":"DeVries F. P., VanDerEden A., Putten J. P. M., Dankert J., Infect. Immun. 64, 2999 (1996).","journal-title":"Infect. Immun."},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","unstructured":"M. P. Jennings et al. Microbiology 145 3013 (1999).","DOI":"10.1099\/00221287-145-11-3013"},{"key":"e_1_3_1_17_2","unstructured":"If the colonizing population of the ancestral capsulated strains is too small a sufficient number of unencapsulated variants (mutants) may not be generated and invasion will not take place. This indeed may well be one of the reasons for the observations that systemic infections are caused by very few of the colonizing bacteria (42\u201344). These situations where a genetic change in the microparasite population is needed to establish systemic infection virulence could well be a consequence of short-sighted evolution of the microparasite in the host rather than an adaptation for the maintenance of the microparasite in the community of hosts (45)."},{"key":"e_1_3_1_18_2","unstructured":"It has been suggested that because of the stochastic nature of the early phase of infections vaccines that are only partially effective could reduce the probability of infection (46)."},{"key":"e_1_3_1_19_2","unstructured":"It may well be that although the infection is cleared by the constitutive defenses an adequate specific immune response may be induced to generate immune memory. This for example may account for why older adults who have never experienced invasive diseases by commensal organisms such as H. influenzae and N. meningititis are much less susceptible to bacterial meningitis than younger individuals."},{"key":"e_1_3_1_20_2","unstructured":"For an example of a mathematical model of this type and a consideration of the motivation for its development its predictions and its role in an experimental study of a bacterial infection see www.eclf.net\/phagocyte.html."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1007\/BF02389870","volume":"12","author":"Craig W.","year":"1993","unstructured":"Craig W., Eur. J. Clin. Microbiol. Infect. Dis. 12, S6 (1993).","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1179\/joc.1997.9.1.38","volume":"9","author":"Drusano G. L.","year":"1997","unstructured":"Drusano G. L., Craig W. A., J. 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This endeavor was supported by grants from the U.S. National Institutes of Health GM33782 and AI40662 (B.R.L.) and GM 54268 (R.A.) and from the Wellcome Trust (B.R.L.)."},{"key":"e_1_3_1_49_2","unstructured":"{newshr}Viewpoint"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1058879","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:33:24Z","timestamp":1704839604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1058879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5,11]]},"references-count":50,"journal-issue":{"issue":"5519","published-print":{"date-parts":[[2001,5,11]]}},"alternative-id":["10.1126\/science.1058879"],"URL":"https:\/\/doi.org\/10.1126\/science.1058879","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5,11]]}}}