Uropathogenic Escherichia coli Colicin-Like Usp and Associated Proteins: Their Evolution and Role in Pathogenesis

In utero, the mammalian fetus normally develops in an environment devoid of microbial challenges. This circumstance changes, however, during and immediately following the birthing process, as the newborn infant becomes colonized by a multitude of environmental bacterial, viral, and fungal species. For the most part, however, rather than causing harm, these microorganisms begin to develop into an individual’s normal microflora. Moreover, many of the body’s organs such as the skin, gastrointestinal, respiratory, and genitourinary tracts, as well as both the nervous and immune systems, continue to develop after birth in close collaboration with the normal microflora [1, 2]. We now realize that normal host development and aging occur in concert with the normal microflora and vice versa and that this process is complex, involving exquisite and complex lines of communication between the host and its normal microflora [3]. Cells of the normal microflora not only receive developmental instructions from the host, but they have also established elaborate signaling pathways for communicating among themselves. These lines of communication allow the different microorganisms within the normal microflora to identify friend from foe, to defend themselves from pathogenic invaders and predatory microbes, to assist each other by providing needed metabolic products and byproducts, and to create environmental niches that favor the colonization process of each member of the community. This process is evolutionary and, under normal circumstances, will lead to a mutual coexistence of the host with its normalmicroflora. Itmay be helpful for hypothesis generation to consider the host and the normal microflora as 2 coexisting complex multicellular individuals, both of which depend on each other to maintain a state of mutual health. The importance of the host–normal microflora relationship is further illustrated when the normal microflora is perturbed in some way, as occurs, for example, during antibiotic use or certain infectious diseases. These changes can lead to drastic alternations in both the total number and diversity of the species in the normal microflora, a situation referred to as dysbiosis. When dysbiosis happens, other environmental opportunistic microbial species can sometimes gain access and establish a foothold in host sites, with pathogenic consequences. Clostridium difficile [4] is one example. Infections can also lead to acute and chronic states of dysbiosis, which then place the host at risk for developing potentially lifelong disorders, such as inflammatory or irritable bowel syndrome, which will then lead to a permanent alteration in the host’s normal microflora [5]. The “hygiene theory,” in which the lack of exposure to certain beneficial microbes at critical stages in a host’s developmental program may be linked to certain allergies, may also represent a form of dysbiosis [6]. To coexist, microbes have evolved numerous mechanisms for communicating with each other. These mechanisms include quorum-sensing molecules [7]; mechanisms for acquiring nutrients such as iron [8], which are critical to survival; and elaborate systems, such as colicins Received 16 May 2013; accepted 17 May 2013; electronically published 30 August 2013. Correspondence: G. D. Armstrong, PhD, Department of Microbiology, Immunology, and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1 (glen.armstrong@ucalgary.ca). The Journal of Infectious Diseases 2013;208:1539–41 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit482