Proteomes of pathogenic Escherichia coli/Shigella group surveyed in their host environments Expert Rev. Proteomics Early online, 1–17 (2014) Moo-Jin Suh 1‡ , Srilatha Kuntumalla 2‡ , Yanbao Yu 1‡ and Rembert Pieper* 1 1 J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA 2 MedImmune, One MedImmune Drive, Gaithersburg, MD 20878, USA *Author for correspondence: Tel.: +1 301 795 7605 rpieper@jcvi.org ‡ Authors contributed equally Proteomic studies on Shigella dysenteriae, Shigella flexneri, enterohemorrhagic Escherichia coli and uropathogenic E. coli (UPEC) are reviewed. UPEC causes infections in the urogenital tract, whereas the other species colonize and, to varying degrees, invade the intestinal tract. Type III secretion systems used to breach the mucosal barrier by the intestinal pathogens revealed distinct expression patterns in different host environments. Dynamic adaptations to changes in nutrient availability and oxygen were observed, including increased reliance on anaerobic respiration and mixed acid fermentation in vivo. Utilization of carbon and nitrogen resources by the bacteria varied considerably depending on the host model investigated. Shigellae and UPEC adapted to metal ion sequestration in the mammalian host by enhancing expression of various receptors and transporters for iron and zinc. This appears to reflect the preferred intracellular life stage of Shigella spp. and responses of UPEC to high levels of lipocalin and lactotransferrin in the urinary tract. KEYWORDS: Escherichia coli proteome • fitness adaptation • host–pathogen interaction • mass spectrometry • Shigella proteome • virulence Escherichia coli is an abundant, facultative anaerobic, Gram-negative bacterium naturally occurring in the mammalian intestinal tract as a constituent of a complex microbiome. It is enriched in the mucus layer of the colon and effectively utilizes complex carbohydrate resources of the mucus and its degradation products, derived in part from the metabolism of anaerobic commensal species in the gut as energy resources. Non-pathogenic and patho- genic E. coli strains share a core genome, which is responsible for the ability of the bac- teria to grow, to coordinate biosynthetic pro- cesses with a versatile energy metabolism and adapt to and compete for ambient nutrient resources. It also allows the bacteria to respond effectively to general stress conditions includ- ing acidic pH and production of antimicrobial compounds by other commensal microbes and the mammalian host’s immune system [1]. Pathogenic E. coli considered to include Shigella species based on comparative genomic data have acquired so-called pathogenicity islands, most of which were acquired via phage DNA integration, and extra-chromosomal DNA, virulence plasmids in particular [1]. The functions encoded by these mobile genetic ele- ments have allowed E. coli strains to adapt to new niches, including additional mammalian hosts, specific organs in the human body such as the bladder and urogenital tract and intra- cellular life styles following permeation of the mucosal barrier of the intestine and cell inva- sion [2]. Shigella genomes were mainly influ- enced by mobile genetic elements. There is evidence for the occurrence of convergent evo- lution via horizontal gene transfer, resulting in marked differences in mechanisms of pathoge- nicity. Substantial knowledge has emerged supporting the notion that genetic traits influ- encing fitness and virulence of E. coli strain variants have contributed to their adaptation to their preferred environmental niches and resistance to human host defenses [1,3]. During the last 15 years, pioneering technologies such as mass spectrometry, shotgun proteomics and specific bioinformatics and computational resources providing accurate links between informahealthcare.com 10.1586/14789450.2014.935342 Ó 2014 Informa UK Ltd ISSN 1478-9450 1 Review Expert Review of Proteomics Downloaded from informahealthcare.com by 192.207.234.194 on 08/29/14 For personal use only.