Indoleamine 2,3 dioxygenase, age, and immune activation in people living with HIV.

Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines the relationship of IDO activity, bacterial translocation, and aging in people living with HIV (PLWH) on ART. Samples and data from PLWH on ART from the Centers for AIDS Research Network of Integrated Clinical Systems and from matched HIV-uninfected patients (controls) from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study were analyzed. The ratio of K to T (K:T) and neopterin were indicators of inflammation; 16S ribosomal DNA (16S rDNA) and lipopolysaccharide (LPS) were markers of bacterial translocation. Samples and data from 205 PLWH and 99 controls were analyzed. PLWH had higher K:T values across all ages, with a significant relationship between age and K:T for both groups. CD4 count or CD4 nadir had no association with K:T. There was no positive association between level of 16S rDNA or LPS detection and K:T. K:T and neopterin were associated. PLWH had elevated IDO activity, at younger ages, despite ART. This study suggests K:T ratio increases with age in both groups and is elevated in PLWH at all ages compared with age-matched controls.

The Campylobacter jejuni Response Regulator and Cyclic-Di-GMP Binding CbrR Is a Novel Regulator of Flagellar Motility.

A leading cause of bacterial gastroenteritis, Campylobacter jejuni is also associated with broad sequelae, including extragastrointestinal conditions such as reactive arthritis and Guillain-Barré Syndrome (GBS). CbrR is a C. jejuni response regulator that is annotated as a diguanylate cyclase (DGC), an enzyme that catalyzes the synthesis of c-di-GMP, a universal bacterial second messenger, from GTP. In C. jejuni DRH212, we constructed an unmarked deletion mutant, cbrR-, and complemented mutant, cbrR+. Motility assays indicated a hyper-motile phenotype associated with cbrR-, whereas motility was deficient in cbrR+. The overexpression of CbrR in cbrR+ was accompanied by a reduction in expression of FlaA, the major flagellin. Biofilm assays and scanning electron microscopy demonstrated similarities between DRH212 and cbrR-; however, cbrR+ was unable to form significant biofilms. Transmission electron microscopy showed similar cell morphology between the three strains; however, cbrR+ cells lacked flagella. Differential radial capillary action of ligand assays (DRaCALA) showed that CbrR binds GTP and c-di-GMP. Liquid chromatography tandem mass spectrometry detected low levels of c-di-GMP in C. jejuni and in E. coli expressing CbrR. CbrR is therefore a negative regulator of FlaA expression and motility, a critical virulence factor in C. jejuni pathogenesis.

Binding of Campylobacter jejuni FliW Adjacent to the CsrA RNA-Binding Pockets Modulates CsrA Regulatory Activity.

Campylobacter jejuni CsrA is an mRNA-binding, post-transcriptional regulator that controls many metabolic- and virulence-related characteristics of this important pathogen. In contrast to E. coli CsrA, whose activity is modulated by binding to small non-coding RNAs (sRNAs), C. jejuni CsrA activity is controlled by binding to the CsrA antagonist FliW. In this study, we identified the FliW binding site on CsrA. Deletion of the C-terminus of C. jejuni CsrA, which is extended relative to sRNA-binding CsrA proteins, abrogated FliW binding. Bacterial two-hybrid experiments were used to assess the interaction of FliW with wild-type CsrA and mutants thereof, in which every amino acid was individually mutated. Two CsrA mutations (V51A and N55A) resulted in a significant decrease in FliW binding. The V51A and N55A mutants also showed a decrease in CsrA-FliW complex formation, as assessed by size-exclusion chromatography and surface plasmon resonance. These residues were highly conserved in bacterial species containing CsrA orthologs whose activities are predicted to be regulated by FliW. The location of FliW binding was immediately adjacent to the two RNA-binding sites of the CsrA homodimer, suggesting the model that FliW binding to CsrA modulates its ability to bind to its mRNA targets either by steric hindrance, electrostatic repulsion, or by altering the overall structure of the RNA-binding sites.

RNA Binding by the Campylobacter jejuni Post-transcriptional Regulator CsrA.

Campylobacter jejuni is a Gram-negative rod-shaped bacterium that commensally inhabits the intestinal tracts of livestock and birds, and which also persists in surface waters. C. jejuni is a leading cause of foodborne gastroenteritis, and these infections are sometimes associated with the development of post-infection sequelae such as Guillain-Barré Syndrome. Flagella are considered a primary virulence factor in C. jejuni, as these organelles are required for pathogenicity-related phenotypes including motility, biofilm formation, host cell interactions, and host colonization. The post-transcriptional regulator CsrA regulates the expression of the major flagellin FlaA by binding to flaA mRNA and repressing its translation. Additionally, CsrA has previously been shown to regulate 120-150 proteins involved in diverse cellular processes. The amino acid sequence of C. jejuni CsrA is significantly different from that of Escherichia coli CsrA, and no previous research has defined the amino acids of C. jejuni CsrA that are critical for RNA binding. In this study, we used in vitro SELEX to identify the consensus RNA sequence mAwGGAs to which C. jejuni CsrA binds with high affinity. We performed saturating site-directed mutagenesis on C. jejuni CsrA and assessed the regulatory activity of these mutant proteins, using a reporter system encoding the 5' untranslated region (5' UTR) upstream of flaA linked translationally to the C. jejuni astA gene. These assays allowed us to identify 19 amino acids that were involved in RNA binding by CsrA, with many but not all of these amino acids clustered in predicted beta strands that are involved in RNA binding by E. coli CsrA. Decreased flaA mRNA binding by mutant CsrA proteins L2A and A36V was confirmed by electrophoretic mobility shift assays. The majority of the amino acids implicated in RNA binding were conserved among diverse Campylobacter species.

FliW controls growth-phase expression of Campylobacter jejuni flagellar and non-flagellar proteins via the post-transcriptional regulator CsrA.

Campylobacter jejuni is an important human pathogen that causes 96 million cases of acute diarrheal disease worldwide each year. We have shown that C. jejuni CsrA is involved in the post-transcriptional regulation of more than 100 proteins, and altered expression of these proteins is presumably involved in the altered virulence-related phenotypes of a csrA mutant. Mutation of fliW results in C. jejuni cells that have greatly truncated flagella, are less motile, less able to form biofilms, and exhibit a reduced ability to colonize chicks. The loss of FliW results in the altered expression of 153 flagellar and non-flagellar proteins, the majority of which are members of the CsrA regulon. The number of proteins dysregulated in the fliW mutant was greater at mid-log phase (120 proteins) than at stationary phase (85 proteins); 52 proteins showed altered expression at both growth phases. Loss of FliW altered the growth-phase- and CsrA-mediated regulation of FlaA flagellin. FliW exerts these effects by binding to both FlaA and to CsrA, as evidenced by pull-down assays, protein-protein cross-linking, and size-exclusion chromatography. Taken together, these results show that CsrA-mediated regulation of both flagellar and non-flagellar proteins is modulated by direct binding of CsrA to the flagellar chaperone FliW. Changing FliW:CsrA stoichiometries at different growth phases allow C. jejuni to couple the expression of flagellar motility to metabolic and virulence characteristics.

Effect of butyrate and Lactobacillus GG on a butyrate receptor and transporter during Campylobacter jejuni exposure.

Campylobacter jejuni frequently infects humans causing many gastrointestinal symptoms, fever, fatigue and several long-term debilitating diseases. Current treatment for campylobacteriosis includes rehydration and in some cases, antibiotic therapy. Probiotics are used to treat several gastrointestinal diseases. Butyrate is a short-chain fatty acid known to promote intestinal health. Interaction of butyrate with its respective receptor (HCAR2) and transporter (SLC5A8), both expressed in the intestine, is associated with water and electrolyte absorption as well as providing defense against colon cancer and inflammation. Alterations in gut microbiota influence the presence of HCAR2 and SLC5A8 in the intestine. We hypothesized that adherence and/or invasion of C. jejuni and alterations in HCAR2 and SLC5A8 expression would be minimized with butyrate or Lactobacillus GG (LGG) pretreatment of Caco-2 cells. We found that both C. jejuni adhesion but not invasion was reduced with butyrate pretreatment. While LGG pretreatment did not prevent C. jejuni adhesion, it did result in reduced invasion which was associated with altered cell supernate pH. Both butyrate and LGG protected HCAR2 and SLC5A8 protein expression following C. jejuni infection. These results suggest that the first stages of C. jejuni infection of Caco-2 cells may be minimized by LGG and butyrate pretreatment.

Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization.

Campylobacter jejuni infection is a leading bacterial cause of gastroenteritis and a common antecedent leading to Gullian-Barré syndrome. Our previous data suggested that the RNA-binding protein CsrA plays an important role in regulating several important phenotypes including motility, biofilm formation, and oxidative stress resistance. In this study, we compared the proteomes of wild type, csrA mutant, and complemented csrA mutant C. jejuni strains in an effort to elucidate the mechanisms by which CsrA affects virulence phenotypes. The putative CsrA regulon was more pronounced at stationary phase (111 regulated proteins) than at mid-log phase (25 regulated proteins). Proteins displaying altered expression in the csrA mutant included diverse metabolic functions, with roles in amino acid metabolism, TCA cycle, acetate metabolism, and various other cell processes, as well as pathogenesis-associated characteristics such as motility, chemotaxis, oxidative stress resistance, and fibronectin binding. The csrA mutant strain also showed altered autoagglutination kinetics when compared to the wild type. CsrA specifically bound the 5' end of flaA mRNA, and we demonstrated that CsrA is a growth-phase dependent repressor of FlaA expression. Finally, the csrA mutant exhibited reduced ability to colonize in a mouse model when in competition with the wild type, further underscoring the role of CsrA in C. jejuni colonization and pathogenesis.

EptC of Campylobacter jejuni mediates phenotypes involved in host interactions and virulence.

Campylobacter jejuni is a natural commensal of the avian intestinal tract. However, the bacterium is also the leading cause of acute bacterial diarrhea worldwide and is implicated in development of Guillain-Barré syndrome. Like many bacterial pathogens, C. jejuni assembles complex surface structures that interface with the surrounding environment and are involved in pathogenesis. Recent work in C. jejuni identified a gene encoding a novel phosphoethanolamine (pEtN) transferase, EptC (Cj0256), that plays a promiscuous role in modifying the flagellar rod protein, FlgG; the lipid A domain of lipooligosaccharide (LOS); and several N-linked glycans. In this work, we report that EptC catalyzes the addition of pEtN to the first heptose sugar of the inner core oligosaccharide of LOS, a fourth enzymatic target. We also examine the role pEtN modification plays in circumventing detection and/or killing by host defenses. Specifically, we show that modification of C. jejuni lipid A with pEtN results in increased recognition by the human Toll-like receptor 4-myeloid differentiation factor 2 (hTLR4-MD2) complex, along with providing resistance to relevant mammalian and avian antimicrobial peptides (i.e., defensins). We also confirm the inability of aberrant forms of LOS to activate Toll-like receptor 2 (TLR2). Most exciting, we demonstrate that strains lacking eptC show decreased commensal colonization of chick ceca and reduced colonization of BALB/cByJ mice compared to wild-type strains. Our results indicate that modification of surface structures with pEtN by EptC is key to its ability to promote commensalism in an avian host and to survive in the mammalian gastrointestinal environment.

Campylobacter jejuni CsrA complements an Escherichia coli csrA mutation for the regulation of biofilm formation, motility and cellular morphology but not glycogen accumulation.

BACKGROUND: Although Campylobacter jejuni is consistently ranked as one of the leading causes of bacterial diarrhea worldwide, the mechanisms by which C. jejuni causes disease and how they are regulated have yet to be clearly defined. The global regulator, CsrA, has been well characterized in several bacterial genera and is known to regulate a number of independent pathways via a post transcriptional mechanism, but remains relatively uncharacterized in the genus Campylobacter. Previously, we reported data illustrating the requirement for CsrA in several virulence related phenotypes of C. jejuni strain 81-176, indicating that the Csr pathway is important for Campylobacter pathogenesis. RESULTS: We compared the Escherichia coli and C. jejuni orthologs of CsrA and characterized the ability of the C. jejuni CsrA protein to functionally complement an E. coli csrA mutant. Phylogenetic comparison of E. coli CsrA to orthologs from several pathogenic bacteria demonstrated variability in C. jejuni CsrA relative to the known RNA binding domains of E. coli CsrA and in several amino acids reported to be involved in E. coli CsrA-mediated gene regulation. When expressed in an E. coli csrA mutant, C. jejuni CsrA succeeded in recovering defects in motility, biofilm formation, and cellular morphology; however, it failed to return excess glycogen accumulation to wild type levels. CONCLUSIONS: These findings suggest that C. jejuni CsrA is capable of efficiently binding some E. coli CsrA binding sites, but not others, and provide insight into the biochemistry of C. jejuni CsrA.

Circuitry linking the Csr and stringent response global regulatory systems.

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry.

Development of a novel therapy for Lipo-oligosaccharide-induced experimental neuritis: use of peptide glycomimics.

Recent etiological studies have revealed that molecular mimicry between the lipo-oligosaccharide (LOS) component of Campylobacter jejuni and gangliosides of peripheral nervous system plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS). Previously, we demonstrated GD3 ganglioside molecular mimicry in a model of GBS in Lewis rats by sensitization with GD3-like LOS (LOS(GD3)) from C. jejuni. Since the neuropathophysiological consequences were due largely to the anti-GD3-like antibodies, we subsequently focused our effort upon eliminating the pathogenic antibodies using several strategies to mimic GD3 in this model. Here, we have validated this strategy by the use of peptide glycomimics based on epitopic mimicry between carbohydrates and peptides. We treated rats by i.p. administration of phage-displayed GD3-like peptides. One GD3-like peptide (P(GD3)-4; RHAYRSMAEWGFLYS) induced in treated rats a remarkable restoration of motor nerve functions, as evidenced by improved histopathology, rotarod performance, and motor nerve conduction velocity. P(GD3)-4 effectively decreased the titer of anti-GD3/anti-LOS(GD3) antibodies and ameliorated peripheral nerve dysfunction in the sera of treated rats. The data suggest that peptide glycomimics of ganglioside may be potential powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic anti-ganglioside antibodies.

Effects of sequential Campylobacter jejuni 81-176 lipooligosaccharide core truncations on biofilm formation, stress survival, and pathogenesis.

Campylobacter jejuni is a highly prevalent human pathogen for which pathogenic and stress survival strategies remain relatively poorly understood. We previously found that a C. jejuni strain 81-176 mutant defective for key virulence and stress survival attributes was also hyper-biofilm and hyperreactive to the UV fluorescent dye calcofluor white (CFW). We hypothesized that screening for CFW hyperreactive mutants would identify additional genes required for C. jejuni pathogenesis properties. Surprisingly, two such mutants harbored lesions in lipooligosaccharide (LOS) genes (waaF and lgtF), indicating a complete loss of the LOS outer core region. We utilized this as an opportunity to explore the role of each LOS core-specific moiety in the pathogenesis and stress survival of this strain and thus also constructed DeltagalT and DeltacstII mutants with more minor LOS truncations. Interestingly, we found that mutants lacking the LOS outer core (DeltawaaF and DeltalgtF but not DeltagalT or DeltacstII mutants) exhibited enhanced biofilm formation. The presence of the complete outer core was also necessary for resistance to complement-mediated killing. In contrast, any LOS truncation, even that of the terminal sialic acid (DeltacstII), resulted in diminished resistance to polymyxin B. The cathelicidin LL-37 was found to be active against C. jejuni, with the LOS mutants exhibiting modest but tiled alterations in LL-37 sensitivity. The DeltawaaF mutant but not the other LOS mutant strains also exhibited a defect in intraepithelial cell survival, an aspect of C. jejuni pathogenesis that has only recently begun to be clarified. Finally, using a mouse competition model, we now provide the first direct evidence for the importance of the C. jejuni LOS in host colonization. Collectively, this study has uncovered novel roles for the C. jejuni LOS, highlights the dynamic nature of the C. jejuni cell envelope, and provides insight into the contribution of specific LOS core moieties to stress survival and pathogenesis.

Mutation of PEB4 alters the outer membrane protein profile of Campylobacter jejuni.

Campylobacter jejuni is a significant cause of human gastroenteritis worldwide. In an attempt to further define bacterial factors that influence infectivity, Cj0596 was identified as playing a role in C. jejuni virulence. Cj0596 is a periplasmic chaperone that is similar to proteins involved in outer membrane protein (OMP) folding in other bacteria. Mutation of cj0596 caused an alteration in the levels of eight OMPs, compared with wild-type bacteria. Replacement of the cj0596 mutation with the wild-type cj0596 gene restored a wild-type OMP profile. The altered OMP profile in the cj0596 mutant was accompanied by significant changes in several virulence properties, including an increase in the ability to autoagglutinate, increased susceptibility to several antimicrobial agents, and increased biofilm formation. In summary, mutation of cj0596 alters the C. jejuni OMP profile and leads to changes in OMP-related phenotypes involved in C. jejuni pathogenesis.

Cj0596 is a periplasmic peptidyl prolyl cis-trans isomerase involved in Campylobacter jejuni motility, invasion, and colonization.

BACKGROUND: Campylobacter jejuni is a gastrointestinal pathogen of humans, but part of the normal flora of poultry, and therefore grows well at the respective body temperatures of 37 degrees C and 42 degrees C. Proteomic studies on temperature regulation in C. jejuni strain 81-176 revealed the upregulation at 37 degrees C of Cj0596, a predicted periplasmic chaperone that is similar to proteins involved in outer membrane protein folding and virulence in other bacteria. RESULTS: The cj0596 gene was highly conserved in 24 strains and species of Campylobacter, implying the importance of this gene. To study the role that Cj0596 plays in C. jejuni pathogenesis, a mutant derivative of strain 81-176 was constructed in which the cj0596 gene was precisely deleted. A revertant of this mutant was isolated by restoring the gene to its original chromosomal location using streptomycin counterselection. The cj0596 mutant strain demonstrated a slightly decreased growth rate and lower final growth yield, yet was more motile and more invasive of human intestinal epithelial cells than wild-type. In either single or mixed infections, the mutant was less able to colonize mice than 81-176. The cj0596 mutant also expressed altered levels of several proteins. CONCLUSION: Mutation of cj0596 has an effect on phenotypes related to C. jejuni pathogenesis, probably due to its role in the proper folding of critical outer membrane proteins.

Atypical roles for Campylobacter jejuni amino acid ATP binding cassette transporter components PaqP and PaqQ in bacterial stress tolerance and pathogen-host cell dynamics.

Campylobacter jejuni is a human pathogen causing severe diarrheal disease; however, our understanding of the survival of C. jejuni during disease and transmission remains limited. Amino acid ATP binding cassette (AA-ABC) transporters in C. jejuni have been proposed as important pathogenesis factors. We have investigated a novel AA-ABC transporter system, encoded by cj0467 to cj0469, by generating targeted deletions of cj0467 (the membrane transport component) and cj0469 (the ATPase component) in C. jejuni 81-176. The analyses described here have led us to designate these genes paqP and paqQ, respectively (pathogenesis-associated glutamine [q] ABC transporter permease [P] and ATPase [Q]). We found that loss of either component resulted in amino acid uptake defects, most notably diminished glutamine uptake. Altered resistance to a series of environmental and in vivo stresses was also observed: both mutants were hyperresistant to aerobic and organic peroxide stress, and while the DeltapaqP mutant was also hyperresistant to heat and osmotic shock, the DeltapaqQ mutant was more susceptible than the wild type to the latter two stresses. The DeltapaqP and DeltapaqQ mutants also displayed a surprising but statistically significant increase in recovery from macrophages and epithelial cells in short-term intracellular survival assays. Annexin V, 4',6-diamidino-2-phenylindole (DAPI), and Western blot analyses revealed that macrophages infected with the DeltapaqP or DeltapaqQ mutant exhibited transient but significant decreases in cell death and extracellular signal-regulated kinase-mitogen-activated protein kinase activation compared to levels in wild-type-infected cells. The DeltapaqP mutant was not defective in either short-term or longer-term mouse colonization, consistent with its increased stress survival and diminished host cell damage phenotypes. Collectively, these results demonstrate a unique correlation of an AA-ABC transporter with bacterial stress tolerances and host cell responses to pathogen infection.

Evaluation of procedures for outer membrane isolation from Campylobacter jejuni.

Although infection with Campylobacter jejuni is one of the leading causes of gastroenteritis worldwide, relatively little is known about the factors that are required to elicit a protective immune response. The need for a vaccine against this pathogen is well recognized and a number of vaccine candidates have been tested with varying degrees of success; however, there is still a lack of a suitable vaccine. To gain a better understanding of the outer-membrane protein components of this organism, a 'gold standard' method to purify the outer membrane is needed. Therefore, we attempted to develop a robust and reliable method which resulted in a pure outer-membrane fraction. A total of nine methodologies were examined and analysed by SDS-PAGE and immunoblotting using subcellular markers for the cytoplasm, cytoplasmic membrane and outer membrane. We found that glycine extraction, differential detergent extraction using Triton X-100, serial extraction using 1 M Tris pH 7, spheroplasting by lysozyme and sonication, and carbonate extraction did not produce pure outer-membrane preparations. However, we identified three methods that provided outer-membrane fractions free from subcellular contamination. Isopycnic centrifugation using a 30-60 % sucrose gradient produced seven fractions free from cytoplasmic or cytoplasmic membrane contamination; however, these fractions did not correspond as well as expected with the typical outer-membrane-associated peak (e.g. Escherichia coli or Salmonella). The spheroplast method using lysozyme alone also resulted in pure outer-membrane fraction, as did carbonate washing of this sample. The extraction of outer membranes using N-lauroylsarcosine (Sarkosyl) produced the purest and most reproducible sample. These outer-membrane preparations will be useful for future studies aimed at identifying C. jejuni surface proteins as vaccine components.

The CprS sensor kinase of the zoonotic pathogen Campylobacter jejuni influences biofilm formation and is required for optimal chick colonization.

Campylobacter jejuni, a prevalent cause of bacterial gastroenteritis, must adapt to different environments to be a successful pathogen. We previously identified a C. jejuni two-component regulatory system (Cj1226/7c) as upregulated during cell infections. Analyses described herein led us to designate the system CprRS (Campylobacter planktonic growth regulation). While the response regulator was essential, a cprS sensor kinase mutant was viable. The Delta cprS mutant displayed an apparent growth defect and formed dramatically enhanced and accelerated biofilms independent of upregulation of previously characterized surface polysaccharides. Delta cprS also displayed a striking dose-dependent defect for colonization of chicks and was modestly enhanced for intracellular survival in INT407 cells. Proteomics analyses identified changes consistent with modulation of essential metabolic genes, upregulation of stress tolerance proteins, and increased expression of MOMP and FlaA. Consistent with expression profiling, we observed enhanced motility and secretion in Delta cprS, and decreased osmotolerance and oxidative stress tolerance. We also found that C. jejuni biofilms contain a DNase I-sensitive component and that biofilm formation is influenced by deoxycholate and the metabolic substrate fumarate. These results suggest that CprRS influences expression of factors important for biofilm formation, colonization and stress tolerance, and also add to our understanding of C. jejuni biofilm physiology.

Campylobacter jejuni host tissue tropism: a consequence of its low-carb lifestyle?

Mechanisms underlying virulence properties of Campylobacter jejuni have historically been difficult to identify. In this issue of Cell Host & Microbe, Hofreuter et al. (2008) show that C. jejuni's ability to metabolize glutamine, glutathione, and asparagine affects its ability to colonize specific host tissues. These findings reflect the emerging theme of bacterial physiology directly impacting pathogenesis.

Role of the Campylobacter jejuni Cj1461 DNA methyltransferase in regulating virulence characteristics.

Mutation of the cj1461 predicted methyltransferase gene reduced the motility of Campylobacter jejuni 81-176. Electron microscopy revealed that the mutant strain had flagella but with aberrant structure. The Deltacj1461 mutant was sevenfold more adherent to but 50-fold less invasive of INT-407 human epithelial cells than the wild type.