PMID- 26327312 OWN - NLM STAT- MEDLINE DCOM- 20160520 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 9 DP - 2015 TI - Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli. PG - e0136387 LID - 10.1371/journal.pone.0136387 [doi] LID - e0136387 AB - Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study reveals virulence factors and phenotypic characteristics of MPEC that may play a role in pathogenesis of E. coli mastitis. FAU - Blum, Shlomo E AU - Blum SE AD - Department of Animal Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot, Israel; National Mastitis Reference Center, Department of Bacteriology, Kimron Veterinary Institute, Bet Dagan, Israel; Department of Bacteriology, Kimron Veterinary Institute, Bet Dagan, Israel. FAU - Heller, Elimelech D AU - Heller ED AD - Department of Animal Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot, Israel. FAU - Sela, Shlomo AU - Sela S AD - Microbial Food-Safety Research Unit, Department of Food Quality & Safety, Institute for Postharvest and Food Sciences, The Volcani Center, ARO, Bet Dagan, Israel. FAU - Elad, Daniel AU - Elad D AD - Department of Bacteriology, Kimron Veterinary Institute, Bet Dagan, Israel. FAU - Edery, Nir AU - Edery N AD - Department of Pathology, Kimron Veterinary Institute, Bet Dagan, Israel. FAU - Leitner, Gabriel AU - Leitner G AD - National Mastitis Reference Center, Department of Bacteriology, Kimron Veterinary Institute, Bet Dagan, Israel. LA - eng SI - GENBANK/AJQW00000000 SI - GENBANK/JTFD00000000 SI - GENBANK/JTFE00000000 SI - GENBANK/JTFF00000000 SI - SRA/SRP059659 SI - SRA/SRP059660 SI - SRA/SRP059661 SI - SRA/SRP059662 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150901 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (DNA, Bacterial) RN - 0 (Proteome) RN - 0 (Virulence Factors) SB - IM MH - Animals MH - DNA, Bacterial/genetics MH - Escherichia coli/*genetics/pathogenicity MH - Escherichia coli Infections/microbiology/*veterinary MH - Female MH - Genome, Bacterial/genetics MH - Mammary Glands, Animal/microbiology MH - Mastitis/*microbiology MH - Mice MH - Milk/microbiology MH - Molecular Sequence Data MH - Phenotype MH - Polymorphism, Single Nucleotide/genetics MH - Proteome/genetics MH - Virulence Factors/genetics PMC - PMC4556653 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/09/04 06:00 MHDA- 2016/05/21 06:00 PMCR- 2015/09/01 CRDT- 2015/09/02 06:00 PHST- 2015/04/21 00:00 [received] PHST- 2015/08/04 00:00 [accepted] PHST- 2015/09/02 06:00 [entrez] PHST- 2015/09/04 06:00 [pubmed] PHST- 2016/05/21 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] AID - PONE-D-15-17347 [pii] AID - 10.1371/journal.pone.0136387 [doi] PST - epublish SO - PLoS One. 2015 Sep 1;10(9):e0136387. doi: 10.1371/journal.pone.0136387. eCollection 2015.