@article{altermann_klaenhammer_2011, title={Group-specific comparison of four lactobacilli isolated from human sources using differential blast analysis}, volume={6}, ISSN={["1555-8932"]}, DOI={10.1007/s12263-010-0191-9}, abstractNote={Lactic acid bacteria (LAB) have been used in fermentation processes for centuries. More recent applications including the use of LAB as probiotics have significantly increased industrial interest. Here we present a comparative genomic analysis of four completely sequenced Lactobacillus strains, isolated from the human gastrointestinal tract, versus 25 lactic acid bacterial genomes present in the public database at the time of analysis. Lactobacillus acidophilus NCFM, Lactobacillus johnsonii NCC533, Lactobacillus gasseri ATCC33323, and Lactobacillus plantarum WCFS1are all considered probiotic and widely used in industrial applications. Using Differential Blast Analysis (DBA), each genome was compared to the respective remaining three other Lactobacillus and 25 other LAB genomes. DBA highlighted strain-specific genes that were not represented in any other LAB used in this analysis and also identified group-specific genes shared within lactobacilli. Initial comparative analyses highlighted a significant number of genes involved in cell adhesion, stress responses, DNA repair and modification, and metabolic capabilities. Furthermore, the range of the recently identified potential autonomous units (PAUs) was broadened significantly, indicating the possibility of distinct families within this genetic element. Based on in silico results obtained for the model organism L. acidophilus NCFM, DBA proved to be a valuable tool to identify new key genetic regions for functional genomics and also suggested re-classification of previously annotated genes.}, number={3}, journal={GENES AND NUTRITION}, author={Altermann, Eric and Klaenhammer, Todd R.}, year={2011}, month={Aug}, pages={319–340} }
 @misc{barrangou_azcarate-peril_altermann_duong_klaenhammer_2009, title={Compositions comprising promoter sequences and methods of use}, volume={7,495,092}, number={2009 Feb. 24}, author={Barrangou, R. and Azcarate-Peril, A. and Altermann, E. and Duong, T. and Klaenhammer, T. R.}, year={2009} }
 @misc{klaenhammer_russell_altermann_buck_2009, title={Lactobacillus acidophillus nucleic acid sequences encoding cell surface protein homologues and uses therefore}, volume={7,538,209}, number={2009 May 26}, author={Klaenhammer, T. R. and Russell, W. M. and Altermann, E. and Buck, B. L.}, year={2009} }
 @misc{klaenhammer_altermann_azcarate-peril_mcauliffe_russell_2009, title={Lactobacillus acidophilus nucleic acid sequences encoding stress-related proteins and uses therefor}, volume={7,608,700}, number={1999 Oct. 27}, author={Klaenhammer, T. R. and Altermann, E. and Azcarate-Peril, M. A. and McAuliffe, O. and Russell, W. M.}, year={2009} }
 @misc{klaenhammer_russell_altermann_azcarate-peril_2009, title={Nucleic acid sequences encoding two-component sensing and regulatory proteins, antimicrobial proteins and uses therefor}, volume={7,550,576}, number={2009 Jun 23}, author={Klaenhammer, T. R. and Russell, W. M. and Altermann, E. and Azcarate-Peril, A.}, year={2009} }
 @article{azcarate-peril_altermann_goh_tallon_sanozky-dawes_pfeiler_o'flaherty_buck_dobson_duong_et al._2008, title={Analysis of the genome sequence of Lactobacillus gasseri ATCC 33323 reveals the molecular basis of an autochthonous intestinal organism}, volume={74}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.00054-08}, abstractNote={ABSTRACT This study presents the complete genome sequence of Lactobacillus gasseri ATCC 33323, a neotype strain of human origin and a native species found commonly in the gastrointestinal tracts of neonates and adults. The plasmid-free genome was 1,894,360 bp in size and predicted to encode 1,810 genes. The GC content was 35.3%, similar to the GC content of its closest relatives, L. johnsonii NCC 533 (34%) and L. acidophilus NCFM (34%). Two identical copies of the prophage LgaI (40,086 bp), of the Sfi11-like Siphoviridae phage family, were integrated tandomly in the chromosome. A number of unique features were identified in the genome of L. gasseri that were likely acquired by horizontal gene transfer and may contribute to the survival of this bacterium in its ecological niche. L. gasseri encodes two restriction and modification systems, which may limit bacteriophage infection. L. gasseri also encodes an operon for production of heteropolysaccharides of high complexity. A unique alternative sigma factor was present similar to that of B. caccae ATCC 43185, a bacterial species isolated from human feces. In addition, L. gasseri encoded the highest number of putative mucus-binding proteins (14) among lactobacilli sequenced to date. Selected phenotypic characteristics that were compared between ATCC 33323 and other human L. gasseri strains included carbohydrate fermentation patterns, growth and survival in bile, oxalate degradation, and adhesion to intestinal epithelial cells, in vitro. The results from this study indicated high intraspecies variability from a genome encoding traits important for survival and retention in the gastrointestinal tract.}, number={15}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, publisher={American Society for Microbiology}, author={Azcarate-Peril, M. Andrea and Altermann, Eric and Goh, Yong Jun and Tallon, Richard and Sanozky-Dawes, Rosemary B. and Pfeiler, Erika A. and O'Flaherty, Sarah and Buck, B. Logan and Dobson, Alleson and Duong, Tri and et al.}, year={2008}, month={Aug}, pages={4610–4625} }
 @article{klaenhammer_altermann_pfeiler_buck_goh_o'flaherty_barrangou_duong_2008, title={Functional genomics of probiotic Lactobacilli}, volume={42}, ISSN={["0192-0790"]}, DOI={10.1097/MCG.0b013e31817da140}, abstractNote={Lactic acid bacteria (LAB) have been used in fermentation processes for millennia. Recent applications such as the use of living cultures as probiotics have significantly increased industrial interest. Related bacterial strains can differ significantly in their genotype and phenotype, and features from one bacterial strain or species cannot necessarily be applied to a related one. These strain or family-specific differences often represent unique and applicable traits. Since 2002, the complete genomes of 13 probiotic LABs have been published. The presentation will discuss these genomes and highlight probiotic traits that are predicted, or functionally linked to genetic content. We have conducted a comparative genomic analysis of 4 completely sequenced Lactobacillus strains versus 25 lactic acid bacterial genomes present in the public database at thetime of analysis. Using Differential Blast Analysis, each genome is compared with 3 other Lactobacillus and 25 other LAB genomes. Differential Blast Analysis highlighted strain-specific genes that were not represented in any other LAB used in this analysis and also identified group-specific genes shared within lactobacilli. Lactobacillus-specific genes include mucus-binding proteins involved in cell-adhesion and several transport systems for carbohydrates and amino acids. Comparative genomic analysis has identified gene targets in Lactobacillus acidophilus for functional analysis, including adhesion to mucin and intestinal epithelial cells, acid tolerance, bile tolerance, and quorum sensing. Whole genome transcriptional profiling of L. acidophilus, and isogenic mutants thereof, has revealed the impact of varying conditions (pH, bile, carbohydrates) and food matrices on the expression of genes important to probiotic-linked mechanisms.}, number={8}, journal={JOURNAL OF CLINICAL GASTROENTEROLOGY}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Klaenhammer, Todd R. and Altermann, Eric and Pfeiler, Erika and Buck, Brock Logan and Goh, Yong-Jun and O'Flaherty, Sarah and Barrangou, Rodolphe and Duong, Tri}, year={2008}, month={Sep}, pages={S160–S162} }
 @misc{klaenhammer_altermann_barrangou_russell_duong_2008, title={Lactobacillus acidophilus nucleic acid sequences encoding carbohydrate utilization-related proteins and uses therefor}, volume={7,459,289}, number={2008 Dec. 2}, author={Klaenhammer, T. R. and Altermann, E. and Barrangou, R. and Russell, W. M. and Duong, T.}, year={2008} }
 @misc{klaenhammer_altermann_buck_russell_2008, title={Lactobacillus acidophilus nucleic acid sequences encoding cell surface protein homologues and uses therefore}, volume={7,348,420}, number={2008 Mar. 25}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Klaenhammer, T. R. and Altermann, E. and Buck, B. L. and Russell, W. M.}, year={2008} }
 @misc{klaenhammer_altermann_russell_2008, title={Lactobacillus acidophilus nucleic acid sequences encoding protease homologues and uses therefore}, volume={7,455,992}, number={2008 Nov. 25}, author={Klaenhammer, T. R. and Altermann, E. and Russell, W. M.}, year={2008} }
 @misc{klaenhammer_azcarate-peril_altermann_2008, title={Lactobacillus acidophilus nucleic acids and uses thereof}, volume={7,468,182}, number={2008 Dec. 23}, author={Klaenhammer, T. and Azcarate-Peril, A. and Altermann, E.}, year={2008} }
 @article{konstantinov_smidt_vos_bruijns_singh_valence_molle_lortal_altermann_klaenhammer_et al._2008, title={S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions}, volume={105}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0810305105}, abstractNote={Dendritic cells (DCs) are antigen-presenting cells that play an essential role in mucosal tolerance. They regularly encounter beneficial intestinal bacteria, but the nature of these cellular contacts and the immune responses elicited by the bacteria are not entirely elucidated. Here, we examined the interactions of Lactobacillus acidophilus NCFM and its cell surface compounds with DCs. L. acidophilus NCFM attached to DCs and induced a concentration-dependent production of IL-10, and low IL-12p70. We further demonstrated that the bacterium binds to DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC- specific receptor. To identify the DC-SIGN ligand present on the bacterium, we took advantage of a generated array of L. acidophilus NCFM mutants. A knockout mutant of L. acidophilus NCFM lacking the surface (S) layer A protein (SlpA) was significantly reduced in binding to DC-SIGN. This mutant incurred a chromosomal inversion leading to dominant expression of a second S layer protein, SlpB. In the SlpB-dominant strain, the nature of the interaction of this bacterium with DCs changed dramatically. Higher concentrations of proinflammatory cytokines such as IL-12p70, TNFα, and IL-1β were produced by DCs interacting with the SlpB-dominant strain compared with the parent NCFM strain. Unlike the SlpA-knockout mutant, T cells primed with L. acidophilus NCFM stimulated DCs produced more IL-4. The SlpA–DC-SIGN interaction was further confirmed as purified SlpA protein ligated directly to the DC-SIGN. In conclusion, the major S layer protein, SlpA, of L. acidophilus NCFM is the first probiotic bacterial DC-SIGN ligand identified that is functionally involved in the modulation of DCs and T cells functions.}, number={49}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Konstantinov, Sergey R. and Smidt, Hauke and Vos, Willem M. and Bruijns, Sven C. M. and Singh, Satwinder Kaur and Valence, Florence and Molle, Daniel and Lortal, Sylvie and Altermann, Eric and Klaenhammer, Todd R. and et al.}, year={2008}, month={Dec}, pages={19474–19479} }
 @article{klaenhammer_azcarate-peril_altermann_barrangou_2007, title={Influence of the dairy environment on gene expression and substrate(1-3)}, volume={137}, ISSN={["0022-3166"]}, DOI={10.1093/jn/137.3.748s}, abstractNote={Lactic acid bacteria (LAB) are widely used for the industrial production of fermented dairy products and form a group of related low-GC-content gram-positive bacteria. The major species used in dairy manufacturing are Lactobacillus, Lactococcus, Streptococcus, and Leuconostoc. Traditionally most are applied as starter cultures for dairy fermentations or used as probiotic cultures, delivered in dairy vehicles. The appearance of the genomes of Lactococcus lactis, Bidifobacterium longum, Lactobacillus plantarum, L. johnsonii, L. acidophilus, 2 strains of Streptococcus thermophilus, and pending completion of many draft genomic sequences, is now promoting in-depth investigation into the comparative genetic content of LAB. Moreover, whole-genome transcriptional arrays are quickly revealing critical genes/operons that are coordinately expressed and the impact of environmental factors on expression of multiple gene sets. Comparative genomics between multiple genomes is providing insights into genes that are important in metabolic, physiological, and functional roles for different LAB in the environments they inhabit, ranging from the gastrointestinal tract to milk and acidified dairy products.}, number={3}, journal={JOURNAL OF NUTRITION}, author={Klaenhammer, Todd R. and Azcarate-Peril, M. Andrea and Altermann, Eric and Barrangou, Rodolphe}, year={2007}, month={Mar}, pages={748S–750S} }
 @article{ventura_canchaya_bernini_altermann_barrangou_mcgrath_claesson_li_leahy_walker_et al._2006, title={Comparative genomics and transcriptional analysis of prophages identified in the Genomes of Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus casei}, volume={72}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.72.5.3130-3146.2006}, abstractNote={ABSTRACT Lactobacillus gasseri ATCC 33323, Lactobacillus salivarius subsp. salivarius UCC 118, and Lactobacillus casei ATCC 334 contain one (LgaI), four (Sal1, Sal2, Sal3, Sal4), and one (Lca1) distinguishable prophage sequences, respectively. Sequence analysis revealed that LgaI, Lca1, Sal1, and Sal2 prophages belong to the group of Sfi11-like pac site and cos site Siphoviridae, respectively. Phylogenetic investigation of these newly described prophage sequences revealed that they have not followed an evolutionary development similar to that of their bacterial hosts and that they show a high degree of diversity, even within a species. The attachment sites were determined for all these prophage elements; LgaI as well as Sal1 integrates in tRNA genes, while prophage Sal2 integrates in a predicted arginino-succinate lyase-encoding gene. In contrast, Lca1 and the Sal3 and Sal4 prophage remnants are integrated in noncoding regions in the L. casei ATCC 334 and L. salivarius UCC 118 genomes. Northern analysis showed that large parts of the prophage genomes are transcriptionally silent and that transcription is limited to genome segments located near the attachment site. Finally, pulsed-field gel electrophoresis followed by Southern blot hybridization with specific prophage probes indicates that these prophage sequences are narrowly distributed within lactobacilli.}, number={5}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, publisher={American Society for Microbiology}, author={Ventura, Marco and Canchaya, Carlos and Bernini, Valentina and Altermann, Eric and Barrangou, Rodolphe and McGrath, Stephen and Claesson, Marcus J. and Li, Yin and Leahy, Sinead and Walker, Carey D. and et al.}, year={2006}, month={May}, pages={3130–3146} }
 @article{makarova_slesarev_wolf_sorokin_mirkin_koonin_pavlov_pavlova_karamychev_polouchine_et al._2006, title={Comparative genomics of the lactic acid bacteria}, volume={103}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0607117103}, abstractNote={Lactic acid-producing bacteria are associated with various plant and animal niches and play a key role in the production of fermented foods and beverages. We report nine genome sequences representing the phylogenetic and functional diversity of these bacteria. The small genomes of lactic acid bacteria encode a broad repertoire of transporters for efficient carbon and nitrogen acquisition from the nutritionally rich environments they inhabit and reflect a limited range of biosynthetic capabilities that indicate both prototrophic and auxotrophic strains. Phylogenetic analyses, comparison of gene content across the group, and reconstruction of ancestral gene sets indicate a combination of extensive gene loss and key gene acquisitions via horizontal gene transfer during the coevolution of lactic acid bacteria with their habitats.}, number={42}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, publisher={Proceedings of the National Academy of Sciences}, author={Makarova, K. and Slesarev, A. and Wolf, Y. and Sorokin, A. and Mirkin, B. and Koonin, E. and Pavlov, A. and Pavlova, N. and Karamychev, V. and Polouchine, N. and et al.}, year={2006}, month={Oct}, pages={15611–15616} }
 @article{altermann_russell_azcarate-peril_barrangou_buck_mcauliffe_souther_dobson_duong_callanan_et al._2005, title={Complete genome sequence of the probiotic lactic acid bacterium Lactobacillus acidophilus NCFM}, volume={102}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0409188102}, abstractNote={Lactobacillus acidophilus NCFM is a probiotic bacterium that has been produced commercially since 1972. The complete genome is 1,993,564 nt and devoid of plasmids. The average GC content is 34.71% with 1,864 predicted ORFs, of which 72.5% were functionally classified. Nine phage-related integrases were predicted, but no complete prophages were found. However, three unique regions designated as potential autonomous units (PAUs) were identified. These units resemble a unique structure and bear characteristics of both plasmids and phages. Analysis of the three PAUs revealed the presence of two R/M systems and a prophage maintenance system killer protein. A spacers interspersed direct repeat locus containing 32 nearly perfect 29-bp repeats was discovered and may provide a unique molecular signature for this organism. In silico analyses predicted 17 transposase genes and a chromosomal locus for lactacin B, a class II bacteriocin. Several mucus- and fibronectin-binding proteins, implicated in adhesion to human intestinal cells, were also identified. Gene clusters for transport of a diverse group of carbohydrates, including fructooligosaccharides and raffinose, were present and often accompanied by transcriptional regulators of the lacI family. For protein degradation and peptide utilization, the organism encoded 20 putative peptidases, homologs for PrtP and PrtM, and two complete oligopeptide transport systems. Nine two-component regulatory systems were predicted, some associated with determinants implicated in bacteriocin production and acid tolerance. Collectively, these features within the genome sequence of L. acidophilus are likely to contribute to the organisms' gastric survival and promote interactions with the intestinal mucosa and microbiota.}, number={11}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, publisher={Proceedings of the National Academy of Sciences}, author={Altermann, E and Russell, WM and Azcarate-Peril, MA and Barrangou, R and Buck, BL and McAuliffe, O and Souther, N and Dobson, A and Duong, T and Callanan, M and et al.}, year={2005}, month={Mar}, pages={3906–3912} }
 @article{buck_altermann_svingerud_klaenhammer_2005, title={Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCFM}, volume={71}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.71.12.8344-8351.2005}, abstractNote={ABSTRACT Lactobacilli are major inhabitants of the normal microflora of the gastrointestinal tract, and some select species have been used extensively as probiotic cultures. One potentially important property of these organisms is their ability to interact with epithelial cells in the intestinal tract, which may promote retention and host-bacterial communication. However, the mechanisms by which they attach to intestinal epithelial cells are unknown. The objective of this study was to investigate cell surface proteins in Lactobacillus acidophilus that may promote attachment to intestinal tissues. Using genome sequence data, predicted open reading frames were searched against known protein and protein motif databases to identify four proteins potentially involved in adhesion to epithelial cells. Homologous recombination was used to construct isogenic mutations in genes encoding a mucin-binding protein, a fibronectin-binding protein, a surface layer protein, and two streptococcal R28 homologs. The abilities of the mutants to adhere to intestinal epithelial cells were then evaluated in vitro. Each strain was screened on Caco-2 cells, which differentiate and express markers characteristic of normal small-intestine cells. A significant decrease in adhesion was observed in the fibronectin-binding protein mutant (76%) and the mucin-binding protein mutant (65%). A surface layer protein mutant also showed reduction in adhesion ability (84%), but the effect of this mutation is likely due to the loss of multiple surface proteins that may be embedded in the S-layer. This study demonstrated that multiple cell surface proteins in L. acidophilus NCFM can individually contribute to the organism's ability to attach to intestinal cells in vitro.}, number={12}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Buck, BL and Altermann, E and Svingerud, T and Klaenhammer, TR}, year={2005}, month={Dec}, pages={8344–8351} }
 @article{klaenhammer_peril_barrangou_duong_altermann_2005, title={Genomic Perspectives on Probiotic Lactic Acid Bacteria}, volume={24}, ISBN={1342-1441}, DOI={10.12938/bifidus.24.31}, abstractNote={The lactic acid bacteria are Gram-positive fermentative microorganisms known primarily for their roles as starter cultures and probiotics. The food industry represents one of the largest manufacturing industries in the world and recent trends are rapidly expanding the use of probiotic cultures within functional foods. Understanding and control of lactic acid bacteria is now being revolutionized by genomic sciences and the appearance of the complete genome sequences for Bifidobacterium longum, Lactobacillus johnsonii, Lactobacillus plantarum, and draft sequences for Lactobacillus gasseri and Lactobacillus casei. This explosion of DNA sequence information, accompanied by the development of bioinformatic tools for nucleic acid and protein analysis, now allows rapid characterization of the lactic acid bacteria for their genomic content and expression profiles across the entire genome. Comparative genomics has already revealed important similarities and differences in strains, species, and genera and will likely identify key genetic features responsible for the beneficial properties ascribed to probiotic lactic acid bacteria. Practical genomics for the lactic acid bacteria promises to establish the genetic landscape, correlate genotypes with desirable phenotypes, establish genetic criteria for strain selection, improve culture stability by stress preconditioning, provide opportunities for metabolic engineering, and uncover a mechanistic basis for the beneficial activities of probiotics when delivered in various foods. This presentation will examine the genomic content of probiotic Lactobacillus cultures, compared to those lactic acid bacterial genomes that have appeared recently. In addition, expression profiling by whole genome microarrays will be used to illustrate how environmental conditions encountered during biomanufacturing, fermentation, and the gastrointestinal tract can impact gene expression and culture functionality.}, number={2}, journal={Bioscience and Microflora}, publisher={BMFH Press}, author={Klaenhammer, Todd R. and Peril, Andrea Azcarate and Barrangou, Rodolphe and Duong, Tri and Altermann, Eric}, year={2005}, pages={31–33} }
 @misc{klaenhammer_barrangou_buck_azcarate-peril_altermann_2005, title={Genomic features of lactic acid bacteria effecting bioprocessing and health}, volume={29}, ISSN={["1574-6976"]}, DOI={10.1016/j.femsre.2005.04.007}, abstractNote={The lactic acid bacteria are a functionally related group of organisms known primarily for their bioprocessing roles in food and beverages. More recently, selected members of the lactic acid bacteria have been implicated in a number of probiotic roles that impact general health and well-being. Genomic analyses of multiple members of the lactic acid bacteria, at the genus, species, and strain level, have now elucidated many genetic features that direct their fermentative and probiotic roles. This information is providing an important platform for understanding core mechanisms that control and regulate bacterial growth, survival, signaling, and fermentative processes and, in some cases, potentially underlying probiotic activities within complex microbial and host ecosystems.}, number={3}, journal={FEMS MICROBIOLOGY REVIEWS}, publisher={Wiley-Blackwell}, author={Klaenhammer, TR and Barrangou, R and Buck, BL and Azcarate-Peril, MA and Altermann, E}, year={2005}, month={Aug}, pages={393–409} }
 @article{azcarate-peril_mcauliffe_altermann_lick_russell_klaenhammer_2005, title={Microarray analysis of a two-component regulatory system involved in acid resistance and proteolytic activity in Lactobacillus acidophilus}, volume={71}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.71.10.5794-5804.2005}, abstractNote={ABSTRACT Two-component regulatory systems are one primary mechanism for environmental sensing and signal transduction. Annotation of the complete genome sequence of the probiotic bacterium Lactobacillus acidophilus NCFM revealed nine two-component regulatory systems. In this study, the histidine protein kinase of a two-component regulatory system (LBA1524HPK-LBA1525RR), similar to the acid-related system lisRK from Listeria monocytogenes (P. D. Cotter et al., J. Bacteriol. 181:6840-6843, 1999), was insertionally inactivated. A whole-genome microarray containing 97.4% of the annotated genes of L. acidophilus was used to compare genome-wide patterns of transcription at various pHs between the control and the histidine protein kinase mutant. The expression pattern of approximately 80 genes was affected by the LBA1524HPK mutation. Putative LBA1525RR target loci included two oligopeptide-transport systems present in the L. acidophilus genome, other components of the proteolytic system, and a LuxS homolog, suspected of participating in synthesis of the AI-2 signaling compound. The mutant exhibited lower tolerance to acid and ethanol in logarithmic-phase cells and poor acidification rates in milk. Supplementation of milk with Casamino Acids essentially restored the acid-producing ability of the mutant, providing additional evidence for a role of this two component system in regulating proteolytic activity in L. acidophilus.}, number={10}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Azcarate-Peril, MA and McAuliffe, O and Altermann, E and Lick, S and Russell, WM and Klaenhammer, TR}, year={2005}, month={Oct}, pages={5794–5804} }
 @article{altermann_klaenhammer_2005, title={PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database}, volume={6}, journal={BMC Genomics}, author={Altermann, E. and Klaenhammer, T. R.}, year={2005} }
 @article{lu_altermann_breidt_predki_fleming_klaenhammer_2005, title={Sequence analysis of the Lactobacillus plantarum bacteriophage Phi JL-1}, volume={348}, ISSN={["1879-0038"]}, DOI={10.1016/j.gene.2004.12.052}, abstractNote={The complete genomic sequence of a Lactobacillus plantarum virulent phage PhiJL-1 was determined. The phage possesses a linear, double-stranded, DNA genome consisting of 36,677 bp with a G+C content of 39.36%. A total of 52 possible open reading frames (ORFs) were identified. According to N-terminal amino acid sequencing and bioinformatic analyses, proven or putative functions were assigned to 21 ORFs (41%), including 5 structural protein genes. The PhiJL-1 genome shows functionally related genes clustered together in a genome structure composed of modules for DNA replication, DNA packaging, head and tail morphogenesis, and lysis. This type of modular genomic organization was similar to several other phages infecting lactic acid bacteria. The structural gene maps revealed that the order of the head and tail genes is highly conserved among the genomes of several Siphoviridae phages, allowing the assignment of probable functions to certain uncharacterized ORFs from phage PhiJL-1 and other Siphoviridae phages.}, journal={GENE}, author={Lu, Z and Altermann, E and Breidt, F and Predki, P and Fleming, HP and Klaenhammer, TR}, year={2005}, month={Mar}, pages={45–54} }
 @article{yildirim_lin_hitchins_jaykus_altermann_klaenhammer_kathariou_2004, title={Epidemic clone I-specific genetic markers in strains of Listeria monocytogenes serotype 4b from foods}, volume={70}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.70.7.4158-4164.2004}, abstractNote={ABSTRACT Listeria monocytogenes contamination of ready-to-eat foods has been implicated in numerous outbreaks of food-borne listeriosis. However, the health hazards posed by L. monocytogenes detected in foods may vary, and speculations exist that strains actually implicated in illness may constitute only a fraction of those that contaminate foods. In this study, examination of 34 serogroup 4 (putative or confirmed serotype 4b) isolates of L. monocytogenes obtained from various foods and food-processing environments, without known implication in illness, revealed that many of these strains had methylation of cytosines at GATC sites in the genome, rendering their DNA resistant to digestion by the restriction endonuclease Sau3AI. These strains also harbored a gene cassette with putative restriction-modification system genes as well as other, genomically unlinked genetic markers characteristic of the major epidemic-associated lineage of L. monocytogenes (epidemic clone I), implicated in numerous outbreaks in Europe and North America. This may reflect a relatively high fitness of strains with these genetic markers in foods and food-related environments relative to other serotype 4b strains and may partially account for the repeated involvement of such strains in human food-borne listeriosis.}, number={7}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Yildirim, S and Lin, W and Hitchins, AD and Jaykus, LA and Altermann, E and Klaenhammer, TR and Kathariou, S}, year={2004}, month={Jul}, pages={4158–4164} }
 @article{yildirim_lin_hitchins_jaykus_altermann_klaenhammer_kathariou_2004, title={Epidemic clone I-specific genetic markers in strains of Listeria monocytogenes serotype 4b from foods (vol 70, pg 4158, 2004)}, volume={70}, ISSN={["0099-2240"]}, DOI={10.1128/aem.70.12.7581.2004}, abstractNote={Listeria monocytogenes contamination of ready-to-eat foods has been implicated in numerous outbreaks of food-borne listeriosis. However, the health hazards posed by L. monocytogenes detected in foods may vary, and speculations exist that strains actually implicated in illness may constitute only a fraction of those that contaminate foods. In this study, examination of 34 serogroup 4 (putative or confirmed serotype 4b) isolates of L. monocytogenes obtained from various foods and food-processing environments, without known implication in illness, revealed that many of these strains had methylation of cytosines at GATC sites in the genome, rendering their DNA resistant to digestion by the restriction endonuclease Sau3AI. These strains also harbored a gene cassette with putative restriction-modification system genes as well as other, genomically unlinked genetic markers characteristic of the major epidemic-associated lineage of L. monocytogenes (epidemic clone I), implicated in numerous outbreaks in Europe and North America. This may reflect a relatively high fitness of strains with these genetic markers in foods and food-related environments relative to other serotype 4b strains and may partially account for the repeated involvement of such strains in human food-borne listeriosis. Food contamination by Listeria monocytogenes has been implicated in numerous outbreaks and sporadic cases of human illness. Most commonly implicated in listeriosis are highly processed, ready-to-eat (RTE) foods that are kept refrigerated for various periods of time. At risk for listeriosis are people in the extremes of age, pregnant women and their fetuses, cancer patients, and others experiencing immunosuppression (13, 24, 35, 38). Listeriosis can have severe symptoms (septicemia, meningitis, and stillbirths) and a high mortality rate (20 to 30%). Hence, regulations exist in numerous nations concerning the density (e.g., 1 CFU/25 g) of cells of the etiologic agent permissible in RTE foods. Such regulations are based on the hypothesis that any L. monocytogenes strain that can be detected in RTE foods has the potential to pose serious hazards to human health. The potential hazard posed by listerial contamination of RTE foods can be influenced by the number of cells at the point of consumption, which would depend on conditions of storage, type of food matrix and its impact on growth, presence of competing microflora and antimicrobial agents, etc. In addition, the strain type of L. monocytogenes involved may be of importance. It is likely, based on studies with other bacterial pathogens, that some strains and strain clusters (clonal groups) within the species might be more pathogenic than others. Speculations have been formulated that only a fraction of the strains of L. monocytogenes found in foods may be capable of causing human illness (20). There is indeed evidence that the repertoire of strains ca}, number={12}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Yildirim, S and Lin, W and Hitchins, AD and Jaykus, LA and Altermann, E and Klaenhammer, TR and Kathariou, S}, year={2004}, month={Dec}, pages={7581–7581} }
 @article{evans_swaminathan_graves_altermann_klaenhammer_fink_kernodle_kathariou_2004, title={Genetic markers unique to Listeria monocytogenes serotype 4b differentiate epidemic clone II (hot dog outbreak strains) from other lineages}, volume={70}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.70.4.2383-2390.2004}, abstractNote={ABSTRACT A small number of closely related strains of Listeria monocytogenes serotype 4b, designated epidemic clone I (ECI), have been implicated in numerous outbreaks of food-borne listeriosis described during the past two decades in Europe and North America. In 1998 to 1999, a multistate outbreak traced to contaminated hot dogs involved a different strain type of serotype 4b, with genetic fingerprints rarely encountered before. In spite of the profound economic and public health impact of this outbreak, the implicated bacteria (designated epidemic clone II [ECII]) have remained poorly characterized genetically, and nucleotide sequences specific for these strains have not been reported. Using genome sequence information, PCR, and Southern blots, we identified DNA fragments which appeared to be either absent or markedly divergent in the hot dog outbreak strains but conserved among other serotype 4b strains. PCR with primers derived from these fragments as well as Southern blots with the amplicons as probes readily differentiated ECII from other serotype 4b strains. The serotype 4b-specific region harboring these fragments was adjacent to inlA, which encodes a well-characterized virulence determinant. The findings suggest that ECII strains have undergone divergence in portions of a serotype-specific region that is conserved in other serotype 4b strains. Although the mechanisms that drive this divergence remain to be identified, DNA-based tools from this region can facilitate the detection and further characterization of strains belonging to this lineage.}, number={4}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Evans, MR and Swaminathan, B and Graves, LM and Altermann, E and Klaenhammer, TR and Fink, RC and Kernodle, S and Kathariou, S}, year={2004}, month={Apr}, pages={2383–2390} }
 @article{azcarate-peril_altermann_hoover-fitzula_cano_klaenhammer_2004, title={Identification and inactivation of genetic loci involved with Lactobacillus acidophilus acid tolerance}, volume={70}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.70.9.5315-5322.2004}, abstractNote={ABSTRACT Amino acid decarboxylation-antiporter reactions are one of the most important systems for maintaining intracellular pH between physiological limits under acid stress. We analyzed the Lactobacillus acidophilus NCFM complete genome sequence and selected four open reading frames with similarities to genes involved with decarboxylation reactions involved in acid tolerance in several microorganisms. Putative genes encoding an ornithine decarboxylase, an amino acid permease, a glutamate γ-aminobutyrate antiporter, and a transcriptional regulator were disrupted by insertional inactivation. The ability of L. acidophilus to survive low-pH conditions, such as those encountered in the stomach or fermented dairy foods, was investigated and compared to the abilities of early- and late-stationary-phase cells of the mutants by challenging them with a variety of acidic conditions. All of the integrants were more sensitive to low pH than the parental strain. Interestingly, each integrant also exhibited an adaptive acid response during logarithmic growth, indicating that multiple mechanisms are present and orchestrated in L. acidophilus in response to acid challenge.}, number={9}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Azcarate-Peril, MA and Altermann, E and Hoover-Fitzula, RL and Cano, RJ and Klaenhammer, TR}, year={2004}, month={Sep}, pages={5315–5322} }
 @article{altermann_buck_cano_klaenhammer_2004, title={Identification and phenotypic characterization of the cell-division protein CdpA}, volume={342}, ISSN={["1879-0038"]}, DOI={10.1016/j.gene.2004.08.004}, abstractNote={Analysis of the automated computer annotation of the early draft phase genome of Lactobacillus acidophilus NCFM revealed the previously discovered S-layer gene slpA and an additional partial ORF with weak similarities to S-layer proteins. The entire gene was sequenced to reveal a 1799-bp gene coding for 599 amino acids with a calculated molecular mass of 64.8 kDa. No transcription or translation signals could be determined in close proximity to the 5′-region. However, a strong putative terminator with a free energy of −16.84 kcal/mol was identified directly downstream of the gene. A PSI-Blast analysis showed similarities to members of S-layer proteins, cell-wall associated proteinases and hexosyl-transferases. Calculation of an unrooted phylogenetic tree with other examples of S-layer proteins and proteinases placed the deduced protein separately from both groups. A derivative of L. acidophilus NCFM was constructed by targeted integration into the gene. SDS-PAGE analysis of non-covalently linked proteins of the cell wall of the mutant, compared to the wild type, revealed the loss of a cell-surface protein. Phenotypic analyses of the mutant revealed significant changes in cell morphology, altered responses to various environmental stresses, and lowered cell adhesion. Based on the in silico and functional analyses, we ascertained that this protein plays a role in cell-wall processing during the growth and cell–cell separation and designated the gene as cell-division protein, cdpA.}, number={1}, journal={GENE}, author={Altermann, E and Buck, BL and Cano, R and Klaenhammer, TR}, year={2004}, month={Nov}, pages={189–197} }
 @misc{barrangou_klaenhammer_altermann_2004, title={Lactobacillus acidophilus nucleic acids encoding fructo-oligosaccharide utilization compounds and uses thereof}, volume={7,407,787}, number={2004 Jun 22}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Barrangou, R. and Klaenhammer, T. R. and Altermann, E.}, year={2004} }
 @article{pridmore_berger_desiere_vilanova_barretto_pittet_zwahlen_rouvet_altermann_barrangou_et al._2004, title={The genome sequence of the probiotic intestinal bacterium Lactobacillus johnsonii NCC 533}, volume={101}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0307327101}, abstractNote={Lactobacillus johnsonii NCC 533 is a member of the acidophilus group of intestinal lactobacilli that has been extensively studied for their "probiotic" activities that include, pathogen inhibition, epithelial cell attachment, and immunomodulation. To gain insight into its physiology and identify genes potentially involved in interactions with the host, we sequenced and analyzed the 1.99-Mb genome of L. johnsonii NCC 533. Strikingly, the organism completely lacked genes encoding biosynthetic pathways for amino acids, purine nucleotides, and most cofactors. In apparent compensation, a remarkable number of uncommon and often duplicated amino acid permeases, peptidases, and phosphotransferase-type transporters were discovered, suggesting a strong dependency of NCC 533 on the host or other intestinal microbes to provide simple monomeric nutrients. Genome analysis also predicted an abundance (>12) of large and unusual cell-surface proteins, including fimbrial subunits, which may be involved in adhesion to glycoproteins or other components of mucin, a characteristic expected to affect persistence in the gastrointestinal tract (GIT). Three bile salt hydrolases and two bile acid transporters, proteins apparently critical for GIT survival, were also detected. In silico genome comparisons with the >95% complete genome sequence of the closely related Lactobacillus gasseri revealed extensive synteny punctuated by clear-cut insertions or deletions of single genes or operons. Many of these regions of difference appear to encode metabolic or structural components that could affect the organisms competitiveness or interactions with the GIT ecosystem.}, number={8}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, publisher={Proceedings of the National Academy of Sciences}, author={Pridmore, RD and Berger, B and Desiere, F and Vilanova, D and Barretto, C and Pittet, AC and Zwahlen, MC and Rouvet, M and Altermann, E and Barrangou, R and et al.}, year={2004}, month={Feb}, pages={2512–2517} }
 @article{barrangou_altermann_hutkins_cano_klaenhammer_2003, title={Functional and comparative genomic analyses of an operon involved in fructooligosaccharide utilization by Lactobacillus acidophilus}, volume={100}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1332765100}, abstractNote={Lactobacillus acidophilus is a probiotic organism that displays the ability to use prebiotic compounds such as fructooligosaccharides (FOS), which stimulate the growth of beneficial commensals in the gastrointestinal tract. However, little is known about the mechanisms and genes involved in FOS utilization by Lactobacillus species. Analysis of the L. acidophilus NCFM genome revealed an msm locus composed of a transcriptional regulator of the LacI family, a four-component ATP-binding cassette (ABC) transport system, a fructosidase, and a sucrose phosphorylase. Transcriptional analysis of this operon demonstrated that gene expression was induced by sucrose and FOS but not by glucose or fructose, suggesting some specificity for nonreadily fermentable sugars. Additionally, expression was repressed by glucose but not by fructose, suggesting catabolite repression via two cre-like sequences identified in the promoter–operator region. Insertional inactivation of the genes encoding the ABC transporter substrate-binding protein and the fructosidase reduced the ability of the mutants to grow on FOS. Comparative analysis of gene architecture within this cluster revealed a high degree of synteny with operons in Streptococcus mutans and Streptococcus pneumoniae. However, the association between a fructosidase and an ABC transporter is unusual and may be specific to L. acidophilus. This is a description of a previously undescribed gene locus involved in transport and catabolism of FOS compounds, which can promote competition of beneficial microorganisms in the human gastrointestinal tract.}, number={15}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, publisher={Proceedings of the National Academy of Sciences}, author={Barrangou, R and Altermann, E and Hutkins, R and Cano, R and Klaenhammer, TR}, year={2003}, month={Jul}, pages={8957–8962} }
 @article{lu_breidt_fleming_altermann_klaenhammer_2003, title={Isolation and characterization of a Lactobacillus plantarum bacteriophage, Phi JL-1, from a cucumber fermentation}, volume={84}, ISSN={["1879-3460"]}, DOI={10.1016/S0168-1605(03)00111-9}, abstractNote={A virulent Lactobacillus plantarum bacteriophage, PhiJL-1, was isolated from a commercial cucumber fermentation. The phage was specific for two related strains of L. plantarum, BI7 and its mutant (deficient in malolactate fermenting ability) MU45, which have been evaluated as starter cultures for controlled cucumber fermentation and as biocontrol microorganisms for minimally processed vegetable products. The phage genome of PhiJL-1 was sequenced to reveal a linear, double-stranded DNA (36.7 kbp). Sodium dodecyl sulfate-polyacryamide gel electrophoresis (SDS-PAGE) profiles indicated that PhiJL-1 contains six structural proteins (28, 34, 45, 50, 61, and 76 kDa). Electron microscopy revealed that the phage has an isometric head (59 nm in diameter), a long non-contractile tail (182 nm in length and 11 nm in width), and a complex base plate. The phage belongs to the Bradley group B1 or Siphoviridae family. One-step growth kinetics of the phage showed that the latent period was 35 min, the rise period was 40 min, and the average burst size was 22 phage particles/infected cell. Phage particles (90%) adsorbed to the host cells 20 min after infection. Calcium supplementation (up to 30 mM CaCl(2)) in MRS media did not affect the first cycle of phage adsorption, but promoted rapid phage propagation and cell lysis in the infection cycle subsequent to adsorption. The D values of PhiJL-1 at pH 6.5 were estimated to be 2.7 min at 70 degrees C and 0.2 min at 80 degrees C by a thermal inactivation experiment. Knowledge of the properties of L. plantarum bacteriophage PhiJL-1 may be important for the development of controlled vegetable fermentations.}, number={2}, journal={INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY}, author={Lu, Z and Breidt, F and Fleming, HP and Altermann, E and Klaenhammer, TR}, year={2003}, month={Jul}, pages={225–235} }
 @article{klaenhammer_altermann_arigoni_bolotin_breidt_broadbent_cano_chaillou_deutscher_gasson_et al._2002, title={Discovering lactic acid bacteria by genomics}, volume={82}, DOI={10.1007/978-94-017-2029-8_3}, abstractNote={This review summarizes a collection of lactic acid bacteria that are now undergoing genomic sequencing and analysis. Summaries are presented on twenty different species, with each overview discussing the organisms fundamental and practical significance, environmental habitat, and its role in fermentation, bioprocessing, or probiotics. For those projects where genome sequence data were available by March 2002, summaries include a listing of key statistics and interesting genomic features. These efforts will revolutionize our molecular view of Gram-positive bacteria, as up to 15 genomes from the low GC content lactic acid bacteria are expected to be available in the public domain by the end of 2003. Our collective view of the lactic acid bacteria will be fundamentally changed as we rediscover the relationships and capabilities of these organisms through genomics.}, number={1-4}, journal={Antonie Van Leeuwenhoek}, author={Klaenhammer, T. and Altermann, E. and Arigoni, F. and Bolotin, A. and Breidt, F. and Broadbent, J. and Cano, R. and Chaillou, S. and Deutscher, J. and Gasson, M. and et al.}, year={2002}, pages={29–58} }