Abstract:
:Cystic fibrosis (CF) is caused by mutations in the CFTR gene and is associated with progressive and ultimately fatal infectious lung disease. There can be considerable variability in disease severity among individuals with the same CFTR mutations, and recent genome-wide association studies have identified secondary genetic factors that contribute to this. One of these modifier genes is SLC6A14, which encodes an amino acid transporter. Importantly, variants of this gene have been associated with age at first acquisition of Pseudomonas aeruginosa In this study, we aimed to determine the function of SLC6A14 in airway epithelia and how it might affect colonization by P. aeruginosa We show that SLC6A14 is expressed in respiratory epithelial cells and transports l-arginine out of the airway surface liquid (ASL). Exposure of airway epithelia to flagellin from P. aeruginosa led to upregulation of SLC6A14 expression and increased SLC6A14-dependent uptake of l-arginine from the ASL. In support of the hypothesis that l-arginine affects P. aeruginosa attachment, we showed that l-arginine supplementation promoted P. aeruginosa attachment to an abiotic surface in a dose-dependent manner. In a coculture model, we found that inhibition of SLC6A14-dependent l-arginine transport enhanced P. aeruginosa attachment. In Slc6a14-/y (knockout) mice, P. aeruginosa attachment to lung tissue was also significantly enhanced. Together, these findings suggest that SLC6A14 activity plays a role in the modification of the initial stages of airway infection by altering the level of l-arginine in the ASL, which in turn affects the attachment of P. aeruginosaIMPORTANCE CF patients with shared CFTR gene mutations show significant variability in their clinical presentation of infectious lung disease. Genome-wide association studies have been used to identify secondary genetic factors that may explain the variable susceptibility to infection by opportunistic pathogens, including P. aeruginosa, the leading cause of pathogen-induced lung damage in nonpediatric CF patients. Once identified and characterized, these secondary genetic modifiers may allow for the development of personalized medicine for patients and ultimately the extension of life. In this study, we interrogated the biological role of one of these modifiers, SLC6A14, and showed that it contributes to host defense by depleting extracellular arginine (an attachment-promoting metabolite for P. aeruginosa) from the airway surface liquid.
journal_name
mBiojournal_title
mBioauthors
Di Paola M,Park AJ,Ahmadi S,Roach EJ,Wu YS,Struder-Kypke M,Lam JS,Bear CE,Khursigara CMdoi
10.1128/mBio.02073-17subject
Has Abstractpub_date
2017-12-19 00:00:00issue
6issn
2150-7511pii
mBio.02073-17journal_volume
8pub_type
杂志文章相关文献
mBio文献大全abstract::Type II polyketides are a group of secondary metabolites with various biological activities. In nature, biosynthesis of type II polyketides involves multiple enzymatic steps whereby key enzymes, including ketoacyl-synthase (KSα), chain length factor (KSβ), and acyl carrier protein (ACP), are utilized to elongate the p...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01334-20
更新日期:2020-09-15 00:00:00
abstract:UNLABELLED:Salmonella enterica serovar Typhimurium is one of the most common S. enterica serovars associated with U.S. foodborne outbreaks. S. Typhimurium bacteria isolated from humans exhibit wide-ranging virulence phenotypes in inbred mice, leading to speculation that some strains are more virulent in nature. However...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00154-16
更新日期:2016-03-08 00:00:00
abstract:UNLABELLED:Small colony variants (SCVs) are naturally occurring subpopulations of bacteria. The clinical characteristics and treatment outcomes of patients with prosthetic joint infection (PJI) caused by staphylococcal SCVs are unknown. This study was a retrospective series of 113 patients with staphylococcal PJI, with...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01910-14
更新日期:2014-09-30 00:00:00
abstract::The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02740-18
更新日期:2019-02-05 00:00:00
abstract:UNLABELLED:Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication and contributes to immune evasion in vivo, but the underlying molecular mechanisms remain incompletely defined. Nef interferes with host cell actin dynamics to restrict T lymphocyte responses to chemokine stimulation and T cell recept...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01309-15
更新日期:2015-09-08 00:00:00
abstract:UNLABELLED:Mycobacterium tuberculosis depends on aerobic respiration for growth and utilizes an aa3-type cytochrome c oxidase for terminal electron transfer. Cytochrome c maturation in bacteria requires covalent attachment of heme to apocytochrome c, which occurs outside the cytoplasmic membrane. We demonstrate that in...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00475-13
更新日期:2013-09-17 00:00:00
abstract::Misincorporation of uracil or spontaneous cytidine deamination is a common mutagenic insult to DNA. Herpesviruses encode a viral uracil-DNA glycosylase (vUNG) and a viral dUTPase (vDUT), each with enzymatic and nonenzymatic functions. However, the coordinated roles of these enzymatic activities in gammaherpesvirus pat...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01831-18
更新日期:2018-10-30 00:00:00
abstract::Posttranslational modification of a protein, either alone or in combination with other modifications, can control properties of that protein, such as enzymatic activity, localization, stability, or interactions with other molecules. N-ε-Lysine acetylation is one such modification that has gained attention in recent ye...
journal_title:mBio
pub_type: 杂志文章,评审
doi:10.1128/mBio.02708-18
更新日期:2019-04-09 00:00:00
abstract::Mannitol-1-phosphate dehydrogenase (M1PDH) is a key enzyme in Staphylococcus aureus mannitol metabolism, but its roles in pathophysiological settings have not been established. We performed comprehensive structure-function analysis of M1PDH from S. aureus USA300, a strain of community-associated methicillin-resistant ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02660-18
更新日期:2019-07-09 00:00:00
abstract:UNLABELLED:The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA) signal transduction pathway. In this study, we ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01862-15
更新日期:2016-01-12 00:00:00
abstract::Recent studies have greatly extended our understanding of the microbiota present in and on the human body. Here, advanced sequencing strategies have provided unprecedented analytical power. The important implications that the emerging data have for human health emphasize the need to intensify research in this area (D....
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00408-12
更新日期:2012-11-06 00:00:00
abstract::Bacteriophages are numerically the most abundant DNA-containing entities in the oligotrophic ocean, yet how specific phage populations vary over time and space remains to be fully explored. Here, we conducted a metagenomic time-series survey of double-stranded DNA phages throughout the water column in the North Pacifi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01903-17
更新日期:2017-11-28 00:00:00
abstract:UNLABELLED:Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical r...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00451-13
更新日期:2013-08-13 00:00:00
abstract::Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20, is a ubiquitin-editing enzyme capable of ubiquitination or deubiquitination of its target proteins. In this study, we show that hepatitis C virus (HCV) infection could induce the expression of A20 via the activation of the A20 promoter. The in...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01660-19
更新日期:2019-07-23 00:00:00
abstract::Resistance-nodulation-division (RND) superfamily efflux systems have been widely studied for their role in antibiotic resistance, but their native biological functions remain poorly understood. We previously showed that loss of RND-mediated efflux in Vibrio cholerae resulted in activation of the Cpx two-component regu...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00126-17
更新日期:2017-05-16 00:00:00
abstract::Acute flaccid myelitis (AFM) is a rare but serious illness of the nervous system, specifically affecting the gray matter of the spinal cord, motor-controlling regions of the brain, and cranial nerves. Most cases of AFM are pathogen associated, typically with poliovirus and enterovirus infections, and occur in children...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02370-19
更新日期:2019-10-22 00:00:00
abstract::Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00716-15
更新日期:2015-06-23 00:00:00
abstract::Pseudomonas aeruginosa is an opportunistic pathogen and the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa infections are difficult to treat due to a number of antibiotic resistance mechanisms and the organism's propensity to form multicellular biofilms. Epidemic strains of P....
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01828-18
更新日期:2019-01-29 00:00:00
abstract::Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis represents an important mechanism of virulence that results in pathogen survival both in vitro and in vivo. To identify M. tuberculosis virulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01278-14
更新日期:2014-08-19 00:00:00
abstract::Most bacteria and archaea use the tubulin homologue FtsZ as its central organizer of cell division. In Gram-negative Escherichia coli bacteria, FtsZ recruits cytosolic, transmembrane, periplasmic, and outer membrane proteins, assembling the divisome that facilitates bacterial cell division. One such divisome component...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01346-18
更新日期:2018-09-11 00:00:00
abstract::Throughout history, the yeast Saccharomyces cerevisiae has played a central role in human society due to its use in food production and more recently as a major industrial and model microorganism, because of the many genetic and genomic tools available to probe its biology. However, S. cerevisiae has proven difficult ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01410-18
更新日期:2018-09-25 00:00:00
abstract:UNLABELLED:Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00638-15
更新日期:2015-05-26 00:00:00
abstract::The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02011-17
更新日期:2018-02-06 00:00:00
abstract::The human fungal pathogen Candida albicans causes lethal systemic infections because of its ability to grow and disseminate in a host. The C. albicans plasma membrane is essential for virulence by acting as a protective barrier and through its key roles in interfacing with the environment, secretion of virulence facto...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00254-11
更新日期:2011-12-27 00:00:00
abstract:UNLABELLED:Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during bone infection. To this end, we determined the transcriptome of S. aureus during the acute (day 7) and chronic (day 28)...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01775-14
更新日期:2014-12-23 00:00:00
abstract::The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00695-17
更新日期:2017-06-27 00:00:00
abstract::Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of indiv...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02771-18
更新日期:2019-04-16 00:00:00
abstract:UNLABELLED:In the model eukaryote Saccharomyces cerevisiae, the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high r...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00559-16
更新日期:2016-05-03 00:00:00
abstract::Butanol production by Clostridium acetobutylicum is accompanied by coproduction of acetone and ethanol, which reduces the yield of butanol and increases the production cost. Here, we report development of several clostridial aldehyde/alcohol dehydrogenase (AAD) variants showing increased butanol selectivity by a serie...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02683-18
更新日期:2019-01-22 00:00:00
abstract::Since the original report that Halomonas sp. strain GFAJ-1 was capable of using arsenic instead of phosphorus to sustain growth, additional studies have been conducted, and GFAJ-1 is now considered a highly arsenic-resistant but phosphorus-dependent bacterium. However, the mechanisms supporting the extreme arsenic res...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00515-18
更新日期:2018-05-01 00:00:00